Andrew D. Bowser

CHICAGO – Lenalidomide plus rituximab (R²) had comparable efficacy versus standard chemoimmunotherapy in patients with previously untreated follicular lymphoma, according to results from a phase 3 trial.

RELEVANCE is the first randomized, phase 3 trial to examine a chemotherapy-free regimen in this setting.

Response and progression-free survival (PFS) results were similar for patients who received R² followed by rituximab maintenance and patients assigned to chemotherapy plus rituximab and rituximab maintenance, in study results presented at the annual meeting of the American Society of Clinical Oncology.

“These results show that lenalidomide plus rituximab, which is a novel immunomodulatory approach, is a potential first-line option for patients with follicular lymphoma that require treatment,” said investigator Nathan H. Fowler, MD, of the University of Texas MD Anderson Cancer Center, Houston.

But since the study was designed as a superiority trial, rather than a noninferiority trial, and it failed to meet its primary endpoint of superior complete remission (CR) or CR unconfirmed (CRu) at 120 weeks, said Bruce D. Cheson, MD, head of hematology at Georgetown University, Washington.

R² had a similar PFS overall and in all major patient subgroups, similar overall survival, less nonhematologic toxicity aside from rash, less neutropenia, and fewer infections despite increased use of growth factors in the chemoimmunotherapy arm, Dr. Cheson said in a presentation commenting on the results. “Therefore, I agree with Dr. Fowler’s conclusion that R² can be considered as an option for the front-line therapy of patients with follicular lymphoma,” Dr. Cheson said.

The RELEVANCE study included 1,030 patients (median age, 59 years) with previously untreated, advanced follicular lymphoma requiring treatment. They were randomized 1:1 to either lenalidomide plus rituximab followed by rituximab maintenance, or R-chemotherapy followed by rituximab maintenance.

SOURCE: Fowler NH et al. ASCO 2018, Abstract 7500.

CHICAGO – Lenalidomide plus rituximab (R²) had comparable efficacy versus standard chemoimmunotherapy in patients with previously untreated follicular lymphoma, according to results from a phase 3 trial.

RELEVANCE is the first randomized, phase 3 trial to examine a chemotherapy-free regimen in this setting.

Response and progression-free survival (PFS) results were similar for patients who received R² followed by rituximab maintenance and patients assigned to chemotherapy plus rituximab and rituximab maintenance, in study results presented at the annual meeting of the American Society of Clinical Oncology.

“These results show that lenalidomide plus rituximab, which is a novel immunomodulatory approach, is a potential first-line option for patients with follicular lymphoma that require treatment,” said investigator Nathan H. Fowler, MD, of the University of Texas MD Anderson Cancer Center, Houston.

But since the study was designed as a superiority trial, rather than a noninferiority trial, and it failed to meet its primary endpoint of superior complete remission (CR) or CR unconfirmed (CRu) at 120 weeks, said Bruce D. Cheson, MD, head of hematology at Georgetown University, Washington.

R² had a similar PFS overall and in all major patient subgroups, similar overall survival, less nonhematologic toxicity aside from rash, less neutropenia, and fewer infections despite increased use of growth factors in the chemoimmunotherapy arm, Dr. Cheson said in a presentation commenting on the results. “Therefore, I agree with Dr. Fowler’s conclusion that R² can be considered as an option for the front-line therapy of patients with follicular lymphoma,” Dr. Cheson said.

The RELEVANCE study included 1,030 patients (median age, 59 years) with previously untreated, advanced follicular lymphoma requiring treatment. They were randomized 1:1 to either lenalidomide plus rituximab followed by rituximab maintenance, or R-chemotherapy followed by rituximab maintenance.

SOURCE: Fowler NH et al. ASCO 2018, Abstract 7500.

CHICAGO – Lenalidomide plus rituximab (R²) had comparable efficacy versus standard chemoimmunotherapy in patients with previously untreated follicular lymphoma, according to results from a phase 3 trial.

RELEVANCE is the first randomized, phase 3 trial to examine a chemotherapy-free regimen in this setting.

Response and progression-free survival (PFS) results were similar for patients who received R² followed by rituximab maintenance and patients assigned to chemotherapy plus rituximab and rituximab maintenance, in study results presented at the annual meeting of the American Society of Clinical Oncology.

“These results show that lenalidomide plus rituximab, which is a novel immunomodulatory approach, is a potential first-line option for patients with follicular lymphoma that require treatment,” said investigator Nathan H. Fowler, MD, of the University of Texas MD Anderson Cancer Center, Houston.

But since the study was designed as a superiority trial, rather than a noninferiority trial, and it failed to meet its primary endpoint of superior complete remission (CR) or CR unconfirmed (CRu) at 120 weeks, said Bruce D. Cheson, MD, head of hematology at Georgetown University, Washington.

R² had a similar PFS overall and in all major patient subgroups, similar overall survival, less nonhematologic toxicity aside from rash, less neutropenia, and fewer infections despite increased use of growth factors in the chemoimmunotherapy arm, Dr. Cheson said in a presentation commenting on the results. “Therefore, I agree with Dr. Fowler’s conclusion that R² can be considered as an option for the front-line therapy of patients with follicular lymphoma,” Dr. Cheson said.

The RELEVANCE study included 1,030 patients (median age, 59 years) with previously untreated, advanced follicular lymphoma requiring treatment. They were randomized 1:1 to either lenalidomide plus rituximab followed by rituximab maintenance, or R-chemotherapy followed by rituximab maintenance.

SOURCE: Fowler NH et al. ASCO 2018, Abstract 7500.

©ASCO/Rodney White 2018

CHICAGO—Two agents targeting novel pathways in myeloid malignancies—mivebresib and bencentinib—are showing promise in early studies, according to a speaker at the 2018 ASCO Annual Meeting.

“Both BET and AXL inhibition appear to be new and exciting targets in myeloid malignancies,” said Alice S. Mims, MD, and both have produced responses as single agents.

Dr Mims, of Ohio State University Wexner Medical Center in Columbus, made these observations in a poster discussion presentation that included commentary on the two agents.

Mivebresib (ABBV-075), an inhibitor of bromodomain and extra terminal (BET) proteins, yielded some responses in relapsed/refractory acute myeloid leukemia (AML) patients in a first-in-human study presented at the meeting (abstract 7019*).

Bemcentinib (BGB324), a first-in class selective inhibitor of the AXL tyrosine kinase, also showed activity in preliminary results of a study including patients with relapsed/refractory disease (abstract 7020*).

“It will be important to know individual patient characteristics to determine the potential response predictors,” Dr Mims said.

Mivebresib (NCT02391480)

Mivebresib is the subject of an ongoing phase 1 dose-escalation study in which 23 patients have been treated. That includes 12 who received the BET inhibitor as monotherapy, and 11 who got it in combination with the BCL-2 inhibitor venetoclax, which is indicated in CLL and has breakthrough therapy designation for AML.

Investigators observed responses in 3 of 17 evaluable patients (17.6%), including 1 complete remission with incomplete blood count recovery in a patient on mivebresib monotherapy, plus 1 partial response and 1 patient achieving a morphologic leukemia-free state with the combination.

The most common grade 3/4 treatment-emergent adverse events included anemia in 52%, thrombocytopenia in 44%, and febrile neutropenia in 26% of patients, with no dose-limiting toxicities noted as of this report.

Bemcentinib (NCT02488408)

Bemcentinib is being evaluated in a phase 1/2 trial including patients with relapsed/refractory AML and myelodysplastic syndromes (MDS).

For 32 patients treated so far, 3 patients achieved a complete remission, including 1 AML and 2 MDS patients.

In addition, 3 patients achieved partial response, including 1 MDS and 2 AML patients.

Treatment with bemcentinib was generally well-tolerated, and most adverse events were mild or moderate, investigators reported in their poster.

Pre-treatment levels of soluble AXL were lower in responders compared with non-responders, investigators also noted.

“Soluble AXL levels may be a predictive biomarker for AXL inhibition, but further assessment is necessary,” Dr Mims said. 

*Data presented at the meeting differ from the abstracts.

©ASCO/Rodney White 2018

CHICAGO—Two agents targeting novel pathways in myeloid malignancies—mivebresib and bencentinib—are showing promise in early studies, according to a speaker at the 2018 ASCO Annual Meeting.

“Both BET and AXL inhibition appear to be new and exciting targets in myeloid malignancies,” said Alice S. Mims, MD, and both have produced responses as single agents.

Dr Mims, of Ohio State University Wexner Medical Center in Columbus, made these observations in a poster discussion presentation that included commentary on the two agents.

Mivebresib (ABBV-075), an inhibitor of bromodomain and extra terminal (BET) proteins, yielded some responses in relapsed/refractory acute myeloid leukemia (AML) patients in a first-in-human study presented at the meeting (abstract 7019*).

Bemcentinib (BGB324), a first-in class selective inhibitor of the AXL tyrosine kinase, also showed activity in preliminary results of a study including patients with relapsed/refractory disease (abstract 7020*).

“It will be important to know individual patient characteristics to determine the potential response predictors,” Dr Mims said.

Mivebresib (NCT02391480)

Mivebresib is the subject of an ongoing phase 1 dose-escalation study in which 23 patients have been treated. That includes 12 who received the BET inhibitor as monotherapy, and 11 who got it in combination with the BCL-2 inhibitor venetoclax, which is indicated in CLL and has breakthrough therapy designation for AML.

Investigators observed responses in 3 of 17 evaluable patients (17.6%), including 1 complete remission with incomplete blood count recovery in a patient on mivebresib monotherapy, plus 1 partial response and 1 patient achieving a morphologic leukemia-free state with the combination.

The most common grade 3/4 treatment-emergent adverse events included anemia in 52%, thrombocytopenia in 44%, and febrile neutropenia in 26% of patients, with no dose-limiting toxicities noted as of this report.

Bemcentinib (NCT02488408)

Bemcentinib is being evaluated in a phase 1/2 trial including patients with relapsed/refractory AML and myelodysplastic syndromes (MDS).

For 32 patients treated so far, 3 patients achieved a complete remission, including 1 AML and 2 MDS patients.

In addition, 3 patients achieved partial response, including 1 MDS and 2 AML patients.

Treatment with bemcentinib was generally well-tolerated, and most adverse events were mild or moderate, investigators reported in their poster.

Pre-treatment levels of soluble AXL were lower in responders compared with non-responders, investigators also noted.

“Soluble AXL levels may be a predictive biomarker for AXL inhibition, but further assessment is necessary,” Dr Mims said. 

*Data presented at the meeting differ from the abstracts.

©ASCO/Rodney White 2018

CHICAGO—Two agents targeting novel pathways in myeloid malignancies—mivebresib and bencentinib—are showing promise in early studies, according to a speaker at the 2018 ASCO Annual Meeting.

“Both BET and AXL inhibition appear to be new and exciting targets in myeloid malignancies,” said Alice S. Mims, MD, and both have produced responses as single agents.

Dr Mims, of Ohio State University Wexner Medical Center in Columbus, made these observations in a poster discussion presentation that included commentary on the two agents.

Mivebresib (ABBV-075), an inhibitor of bromodomain and extra terminal (BET) proteins, yielded some responses in relapsed/refractory acute myeloid leukemia (AML) patients in a first-in-human study presented at the meeting (abstract 7019*).

Bemcentinib (BGB324), a first-in class selective inhibitor of the AXL tyrosine kinase, also showed activity in preliminary results of a study including patients with relapsed/refractory disease (abstract 7020*).

“It will be important to know individual patient characteristics to determine the potential response predictors,” Dr Mims said.

Mivebresib (NCT02391480)

Mivebresib is the subject of an ongoing phase 1 dose-escalation study in which 23 patients have been treated. That includes 12 who received the BET inhibitor as monotherapy, and 11 who got it in combination with the BCL-2 inhibitor venetoclax, which is indicated in CLL and has breakthrough therapy designation for AML.

Investigators observed responses in 3 of 17 evaluable patients (17.6%), including 1 complete remission with incomplete blood count recovery in a patient on mivebresib monotherapy, plus 1 partial response and 1 patient achieving a morphologic leukemia-free state with the combination.

The most common grade 3/4 treatment-emergent adverse events included anemia in 52%, thrombocytopenia in 44%, and febrile neutropenia in 26% of patients, with no dose-limiting toxicities noted as of this report.

Bemcentinib (NCT02488408)

Bemcentinib is being evaluated in a phase 1/2 trial including patients with relapsed/refractory AML and myelodysplastic syndromes (MDS).

For 32 patients treated so far, 3 patients achieved a complete remission, including 1 AML and 2 MDS patients.

In addition, 3 patients achieved partial response, including 1 MDS and 2 AML patients.

Treatment with bemcentinib was generally well-tolerated, and most adverse events were mild or moderate, investigators reported in their poster.

Pre-treatment levels of soluble AXL were lower in responders compared with non-responders, investigators also noted.

“Soluble AXL levels may be a predictive biomarker for AXL inhibition, but further assessment is necessary,” Dr Mims said. 

*Data presented at the meeting differ from the abstracts.

CHICAGO – A first-in-class antibody targeting the macrophage checkpoint CD47 is a promising novel immunotherapy in non-Hodgkin lymphoma, according to Ranjana H. Advani, MD, of Stanford (Calif.) Cancer Institute.

Treatment with Hu5F9-G4 (5F9), an antibody designed to overcome the “don’t eat me” signal associated with CD47, produced “encouraging” antitumor activity in a phase 1b study of 22 patients, Dr. Advani said in an oral abstract presentation at the annual meeting of the American Society of Clinical Oncology.

“5F9 was well tolerated in combination with rituximab, with no maximum tolerated dose achieved,” said Dr. Advani, noting that there were complete remissions in 43% of the refractory follicular lymphoma patients and 33% of refractory diffuse large B-cell lymphoma patients in the phase 1b/2 study.

The antibody has an on-target anemia effect that occurs upon administration, but that was mitigated considerably by a priming and maintenance dosing approach, she added.

The study has demonstrated “excellent” response rates in a highly refractory patient population, said Caron A. Jacobson, MD, of Dana-Farber Cancer Institute and Harvard Medical School in Boston. “Targeting CD47 ... really helps to shift the balance from ‘don’t eat me’ to ‘eat me,’ ” Dr. Jacobson said at the meeting.

“Importantly, we saw very little toxicity in the study, with very few grade 4 adverse events and no immune-related adverse events,” she added.

Most adverse events were grade 1 or 2, with the most common being the expected on-target anemia associated with 5F9. Using an initial priming dose of 5F9 results in a “temporary and mild decline” in hemoglobin due to clearance of aged red blood cells, Dr. Advani said.

SOURCE: Advani RH et al. ASCO 2018, abstract 7504.

CHICAGO – A first-in-class antibody targeting the macrophage checkpoint CD47 is a promising novel immunotherapy in non-Hodgkin lymphoma, according to Ranjana H. Advani, MD, of Stanford (Calif.) Cancer Institute.

Treatment with Hu5F9-G4 (5F9), an antibody designed to overcome the “don’t eat me” signal associated with CD47, produced “encouraging” antitumor activity in a phase 1b study of 22 patients, Dr. Advani said in an oral abstract presentation at the annual meeting of the American Society of Clinical Oncology.

“5F9 was well tolerated in combination with rituximab, with no maximum tolerated dose achieved,” said Dr. Advani, noting that there were complete remissions in 43% of the refractory follicular lymphoma patients and 33% of refractory diffuse large B-cell lymphoma patients in the phase 1b/2 study.

The antibody has an on-target anemia effect that occurs upon administration, but that was mitigated considerably by a priming and maintenance dosing approach, she added.

The study has demonstrated “excellent” response rates in a highly refractory patient population, said Caron A. Jacobson, MD, of Dana-Farber Cancer Institute and Harvard Medical School in Boston. “Targeting CD47 ... really helps to shift the balance from ‘don’t eat me’ to ‘eat me,’ ” Dr. Jacobson said at the meeting.

“Importantly, we saw very little toxicity in the study, with very few grade 4 adverse events and no immune-related adverse events,” she added.

Most adverse events were grade 1 or 2, with the most common being the expected on-target anemia associated with 5F9. Using an initial priming dose of 5F9 results in a “temporary and mild decline” in hemoglobin due to clearance of aged red blood cells, Dr. Advani said.

SOURCE: Advani RH et al. ASCO 2018, abstract 7504.

CHICAGO – A first-in-class antibody targeting the macrophage checkpoint CD47 is a promising novel immunotherapy in non-Hodgkin lymphoma, according to Ranjana H. Advani, MD, of Stanford (Calif.) Cancer Institute.

Treatment with Hu5F9-G4 (5F9), an antibody designed to overcome the “don’t eat me” signal associated with CD47, produced “encouraging” antitumor activity in a phase 1b study of 22 patients, Dr. Advani said in an oral abstract presentation at the annual meeting of the American Society of Clinical Oncology.

“5F9 was well tolerated in combination with rituximab, with no maximum tolerated dose achieved,” said Dr. Advani, noting that there were complete remissions in 43% of the refractory follicular lymphoma patients and 33% of refractory diffuse large B-cell lymphoma patients in the phase 1b/2 study.

The antibody has an on-target anemia effect that occurs upon administration, but that was mitigated considerably by a priming and maintenance dosing approach, she added.

The study has demonstrated “excellent” response rates in a highly refractory patient population, said Caron A. Jacobson, MD, of Dana-Farber Cancer Institute and Harvard Medical School in Boston. “Targeting CD47 ... really helps to shift the balance from ‘don’t eat me’ to ‘eat me,’ ” Dr. Jacobson said at the meeting.

“Importantly, we saw very little toxicity in the study, with very few grade 4 adverse events and no immune-related adverse events,” she added.

Most adverse events were grade 1 or 2, with the most common being the expected on-target anemia associated with 5F9. Using an initial priming dose of 5F9 results in a “temporary and mild decline” in hemoglobin due to clearance of aged red blood cells, Dr. Advani said.

SOURCE: Advani RH et al. ASCO 2018, abstract 7504.

Patients with localized prostate cancer who were smokers at the time of local therapy had a higher risk of experiencing adverse outcomes and death related to the disease, a systematic review and meta-analysis has shown.

Current smokers in the study had a higher risk of biochemical recurrence, metastasis, and cancer-specific mortality after undergoing primary radical prostatectomy or radiotherapy.

Brett Mulcahy/ThinkStock

Future studies need to more closely examine the link between smoking cessation and longer-term oncologic outcomes, as well as a more precise assessment of smoking exposure, the researchers concluded.

In the current study, results were inconclusive as to whether former smoking and time to cessation had any relationship to outcomes after radical prostatectomy or radiotherapy.

“Available data were sparse and heterogenous,” they noted.

Dr. Foerster is supported by the Scholarship Foundation of Swiss Urology. One coauthor reported disclosures related to Astellas, Cepheid, Ipsen, Jansen, Lilly, Olympus, Pfizer, Pierre Fabre, Sanochemia, Sanofi, and Wolff.

SOURCE: Foerster B et al. JAMA Oncol. 2018 May 24. doi: 10.1001/jamaoncol.2018.1071.

Patients with localized prostate cancer who were smokers at the time of local therapy had a higher risk of experiencing adverse outcomes and death related to the disease, a systematic review and meta-analysis has shown.

Current smokers in the study had a higher risk of biochemical recurrence, metastasis, and cancer-specific mortality after undergoing primary radical prostatectomy or radiotherapy.

Brett Mulcahy/ThinkStock

Future studies need to more closely examine the link between smoking cessation and longer-term oncologic outcomes, as well as a more precise assessment of smoking exposure, the researchers concluded.

In the current study, results were inconclusive as to whether former smoking and time to cessation had any relationship to outcomes after radical prostatectomy or radiotherapy.

“Available data were sparse and heterogenous,” they noted.

Dr. Foerster is supported by the Scholarship Foundation of Swiss Urology. One coauthor reported disclosures related to Astellas, Cepheid, Ipsen, Jansen, Lilly, Olympus, Pfizer, Pierre Fabre, Sanochemia, Sanofi, and Wolff.

SOURCE: Foerster B et al. JAMA Oncol. 2018 May 24. doi: 10.1001/jamaoncol.2018.1071.

Patients with localized prostate cancer who were smokers at the time of local therapy had a higher risk of experiencing adverse outcomes and death related to the disease, a systematic review and meta-analysis has shown.

Current smokers in the study had a higher risk of biochemical recurrence, metastasis, and cancer-specific mortality after undergoing primary radical prostatectomy or radiotherapy.

Brett Mulcahy/ThinkStock

Future studies need to more closely examine the link between smoking cessation and longer-term oncologic outcomes, as well as a more precise assessment of smoking exposure, the researchers concluded.

In the current study, results were inconclusive as to whether former smoking and time to cessation had any relationship to outcomes after radical prostatectomy or radiotherapy.

“Available data were sparse and heterogenous,” they noted.

Dr. Foerster is supported by the Scholarship Foundation of Swiss Urology. One coauthor reported disclosures related to Astellas, Cepheid, Ipsen, Jansen, Lilly, Olympus, Pfizer, Pierre Fabre, Sanochemia, Sanofi, and Wolff.

SOURCE: Foerster B et al. JAMA Oncol. 2018 May 24. doi: 10.1001/jamaoncol.2018.1071.

©ASCO/Rodney White 2018

CHICAGO—Acalabrutinib monotherapy was highly effective in Waldenström’s macroglobulinemia (WM) in a phase 2 study, investigator Roger Owen, MD, reported at the 2018 ASCO Annual Meeting.

The BTK inhibitor was effective in both treatment-naïve and relapsed/refractory patients, with overall response rates for both groups in excess of 90%, and “amazing” major response rates—partial response or better—of approximately 80%, Dr Owen said.

Dr Owen, of the St James's Institute of Oncology, Leeds Teaching Hospitals NHS Trust in Leeds, UK, reported the findings as abstract 7501.*

Durations of response were excellent, according to Dr Owen, who also reported 2-year progression-free survival of 90% in treatment-naïve patients and 82% in relapsed/refractory patients.

The safety profile was favorable, with most adverse events of low grade, and a very limited number of dropouts due to adverse events, according to the investigator.

“I think this study clearly demonstrates the highly effective nature of acalabrutinib in Waldenström’s macroglobulinemia,” Dr Owen stated.

 Acalabrutinib is a selective BTK inhibitor with minimal off-target activity, he said. The BTK inhibitor ibrutinib also has demonstrated activity in Waldenström’s, but has been associated with toxicities such as atrial fibrillation and bleeding, he noted.

In this phase 2 acalabrutinib study (NCT02180724), which included 14 treatment-naïve and 92 relapsed/refractory patients, atrial fibrillation occurred in 5 patients. However, 4 of those cases were grade 1-2, and only one was grade 3, according to Dr Owen.

Investigators observed grade 3 hypertension in 3 relapsed/refractory patients.

Bleeding events occurred in more than half of patients, though only 3 of those events were grade 3, and no patient discontinued treatment due to a bleeding episode.

These efficacy results are “impressive,” and the fact that very few cardiac events were seen is important, said Bruce D. Cheson, MD, of Georgetown University Medical Center in Washington, DC.

Dr Cheson commented on the acalabrutinib results in his presentation during ASCO on non-chemotherapy treatments for lymphoid malignancies.

 “One can construct a non-chemo algorithm now for Waldenström’s, for patients who are MYD88 mutated, which is more than 90% of patients,” he said. “Right now ibrutinib, and perhaps in the future acalabrutinib, can be the initial therapy with or without rituximab based on the results of ongoing trials.”

However, single non-chemotherapy agents will not be sufficient to achieve cure of lymphoid malignancies, Dr Cheson added.

“We need to carefully develop rational combinations, identifying biomarkers for response, for resistance, for toxicity,” he said.

The study was sponsored by Acerta Pharma BV. 

*Data presented at the meeting differ from the abstract.

©ASCO/Rodney White 2018

CHICAGO—Acalabrutinib monotherapy was highly effective in Waldenström’s macroglobulinemia (WM) in a phase 2 study, investigator Roger Owen, MD, reported at the 2018 ASCO Annual Meeting.

The BTK inhibitor was effective in both treatment-naïve and relapsed/refractory patients, with overall response rates for both groups in excess of 90%, and “amazing” major response rates—partial response or better—of approximately 80%, Dr Owen said.

Dr Owen, of the St James's Institute of Oncology, Leeds Teaching Hospitals NHS Trust in Leeds, UK, reported the findings as abstract 7501.*

Durations of response were excellent, according to Dr Owen, who also reported 2-year progression-free survival of 90% in treatment-naïve patients and 82% in relapsed/refractory patients.

The safety profile was favorable, with most adverse events of low grade, and a very limited number of dropouts due to adverse events, according to the investigator.

“I think this study clearly demonstrates the highly effective nature of acalabrutinib in Waldenström’s macroglobulinemia,” Dr Owen stated.

 Acalabrutinib is a selective BTK inhibitor with minimal off-target activity, he said. The BTK inhibitor ibrutinib also has demonstrated activity in Waldenström’s, but has been associated with toxicities such as atrial fibrillation and bleeding, he noted.

In this phase 2 acalabrutinib study (NCT02180724), which included 14 treatment-naïve and 92 relapsed/refractory patients, atrial fibrillation occurred in 5 patients. However, 4 of those cases were grade 1-2, and only one was grade 3, according to Dr Owen.

Investigators observed grade 3 hypertension in 3 relapsed/refractory patients.

Bleeding events occurred in more than half of patients, though only 3 of those events were grade 3, and no patient discontinued treatment due to a bleeding episode.

These efficacy results are “impressive,” and the fact that very few cardiac events were seen is important, said Bruce D. Cheson, MD, of Georgetown University Medical Center in Washington, DC.

Dr Cheson commented on the acalabrutinib results in his presentation during ASCO on non-chemotherapy treatments for lymphoid malignancies.

 “One can construct a non-chemo algorithm now for Waldenström’s, for patients who are MYD88 mutated, which is more than 90% of patients,” he said. “Right now ibrutinib, and perhaps in the future acalabrutinib, can be the initial therapy with or without rituximab based on the results of ongoing trials.”

However, single non-chemotherapy agents will not be sufficient to achieve cure of lymphoid malignancies, Dr Cheson added.

“We need to carefully develop rational combinations, identifying biomarkers for response, for resistance, for toxicity,” he said.

The study was sponsored by Acerta Pharma BV. 

*Data presented at the meeting differ from the abstract.

©ASCO/Rodney White 2018

CHICAGO—Acalabrutinib monotherapy was highly effective in Waldenström’s macroglobulinemia (WM) in a phase 2 study, investigator Roger Owen, MD, reported at the 2018 ASCO Annual Meeting.

The BTK inhibitor was effective in both treatment-naïve and relapsed/refractory patients, with overall response rates for both groups in excess of 90%, and “amazing” major response rates—partial response or better—of approximately 80%, Dr Owen said.

Dr Owen, of the St James's Institute of Oncology, Leeds Teaching Hospitals NHS Trust in Leeds, UK, reported the findings as abstract 7501.*

Durations of response were excellent, according to Dr Owen, who also reported 2-year progression-free survival of 90% in treatment-naïve patients and 82% in relapsed/refractory patients.

The safety profile was favorable, with most adverse events of low grade, and a very limited number of dropouts due to adverse events, according to the investigator.

“I think this study clearly demonstrates the highly effective nature of acalabrutinib in Waldenström’s macroglobulinemia,” Dr Owen stated.

 Acalabrutinib is a selective BTK inhibitor with minimal off-target activity, he said. The BTK inhibitor ibrutinib also has demonstrated activity in Waldenström’s, but has been associated with toxicities such as atrial fibrillation and bleeding, he noted.

In this phase 2 acalabrutinib study (NCT02180724), which included 14 treatment-naïve and 92 relapsed/refractory patients, atrial fibrillation occurred in 5 patients. However, 4 of those cases were grade 1-2, and only one was grade 3, according to Dr Owen.

Investigators observed grade 3 hypertension in 3 relapsed/refractory patients.

Bleeding events occurred in more than half of patients, though only 3 of those events were grade 3, and no patient discontinued treatment due to a bleeding episode.

These efficacy results are “impressive,” and the fact that very few cardiac events were seen is important, said Bruce D. Cheson, MD, of Georgetown University Medical Center in Washington, DC.

Dr Cheson commented on the acalabrutinib results in his presentation during ASCO on non-chemotherapy treatments for lymphoid malignancies.

 “One can construct a non-chemo algorithm now for Waldenström’s, for patients who are MYD88 mutated, which is more than 90% of patients,” he said. “Right now ibrutinib, and perhaps in the future acalabrutinib, can be the initial therapy with or without rituximab based on the results of ongoing trials.”

However, single non-chemotherapy agents will not be sufficient to achieve cure of lymphoid malignancies, Dr Cheson added.

“We need to carefully develop rational combinations, identifying biomarkers for response, for resistance, for toxicity,” he said.

The study was sponsored by Acerta Pharma BV. 

*Data presented at the meeting differ from the abstract.

CHICAGO – Minimal residual disease (MRD)–negative complete remission was strongly associated with improved survival outcomes in patients with B-cell acute lymphocytic leukemia (ALL) who received CD19 chimeric antigen receptor (CAR) T cells, results of a retrospective study showed.

Allogeneic hematopoietic stem cell transplant (HSCT) appeared to improve both disease-free and overall survival in those patients who had achieved MRD-negative complete remission, according to results of the study, which were presented at the annual meeting of the American Society of Clinical Oncology.

“Based upon our interaction testing, the potential benefit [of transplant] appears to exist in both good-risk and bad-risk patients as identified through multivariate modeling,” said study investigator Kevin Anthony Hay, MD, of Fred Hutchinson Cancer Research Center, Seattle.

In a comment on the results, Sarah Cooley, MD, noted that the benefits of allogeneic transplant were apparent regardless of whether the patients met criteria for the good-risk subgroup, which was defined by levels of lactate dehydrogenase (LDH) and platelets along with exposure to fludarabine as part of the conditioning regimen.

“I think this suggests that the goal at this point is to get patients to an MRD-negative state and to potentially curative transplant,” said Dr. Cooley, director of investigator-initiated research at Masonic Medical Center at the University of Minnesota, Minneapolis.

The retrospective analysis by Dr. Hay and his colleagues included 53 adults with relapsed or refractory ALL who had bone marrow or extramedullary disease at baseline and had received CD19 CAR T cells at or under the maximum tolerated dose at least 1 year prior to this analysis. Of that group, 45 (85%) achieved MRD-negative complete remission.

Those patients who did achieve MRD-negative complete remission had an improved median disease-free survival at 7.6 months versus 0.8 months (P less than .0001) and improved overall survival at 20.0 months versus 5.0 months (P = 0.014).

SOURCE: Hay KA. ASCO 2018, Abstract 7005.

CHICAGO – Minimal residual disease (MRD)–negative complete remission was strongly associated with improved survival outcomes in patients with B-cell acute lymphocytic leukemia (ALL) who received CD19 chimeric antigen receptor (CAR) T cells, results of a retrospective study showed.

Allogeneic hematopoietic stem cell transplant (HSCT) appeared to improve both disease-free and overall survival in those patients who had achieved MRD-negative complete remission, according to results of the study, which were presented at the annual meeting of the American Society of Clinical Oncology.

“Based upon our interaction testing, the potential benefit [of transplant] appears to exist in both good-risk and bad-risk patients as identified through multivariate modeling,” said study investigator Kevin Anthony Hay, MD, of Fred Hutchinson Cancer Research Center, Seattle.

In a comment on the results, Sarah Cooley, MD, noted that the benefits of allogeneic transplant were apparent regardless of whether the patients met criteria for the good-risk subgroup, which was defined by levels of lactate dehydrogenase (LDH) and platelets along with exposure to fludarabine as part of the conditioning regimen.

“I think this suggests that the goal at this point is to get patients to an MRD-negative state and to potentially curative transplant,” said Dr. Cooley, director of investigator-initiated research at Masonic Medical Center at the University of Minnesota, Minneapolis.

The retrospective analysis by Dr. Hay and his colleagues included 53 adults with relapsed or refractory ALL who had bone marrow or extramedullary disease at baseline and had received CD19 CAR T cells at or under the maximum tolerated dose at least 1 year prior to this analysis. Of that group, 45 (85%) achieved MRD-negative complete remission.

Those patients who did achieve MRD-negative complete remission had an improved median disease-free survival at 7.6 months versus 0.8 months (P less than .0001) and improved overall survival at 20.0 months versus 5.0 months (P = 0.014).

SOURCE: Hay KA. ASCO 2018, Abstract 7005.

CHICAGO – Minimal residual disease (MRD)–negative complete remission was strongly associated with improved survival outcomes in patients with B-cell acute lymphocytic leukemia (ALL) who received CD19 chimeric antigen receptor (CAR) T cells, results of a retrospective study showed.

Allogeneic hematopoietic stem cell transplant (HSCT) appeared to improve both disease-free and overall survival in those patients who had achieved MRD-negative complete remission, according to results of the study, which were presented at the annual meeting of the American Society of Clinical Oncology.

“Based upon our interaction testing, the potential benefit [of transplant] appears to exist in both good-risk and bad-risk patients as identified through multivariate modeling,” said study investigator Kevin Anthony Hay, MD, of Fred Hutchinson Cancer Research Center, Seattle.

In a comment on the results, Sarah Cooley, MD, noted that the benefits of allogeneic transplant were apparent regardless of whether the patients met criteria for the good-risk subgroup, which was defined by levels of lactate dehydrogenase (LDH) and platelets along with exposure to fludarabine as part of the conditioning regimen.

“I think this suggests that the goal at this point is to get patients to an MRD-negative state and to potentially curative transplant,” said Dr. Cooley, director of investigator-initiated research at Masonic Medical Center at the University of Minnesota, Minneapolis.

The retrospective analysis by Dr. Hay and his colleagues included 53 adults with relapsed or refractory ALL who had bone marrow or extramedullary disease at baseline and had received CD19 CAR T cells at or under the maximum tolerated dose at least 1 year prior to this analysis. Of that group, 45 (85%) achieved MRD-negative complete remission.

Those patients who did achieve MRD-negative complete remission had an improved median disease-free survival at 7.6 months versus 0.8 months (P less than .0001) and improved overall survival at 20.0 months versus 5.0 months (P = 0.014).

SOURCE: Hay KA. ASCO 2018, Abstract 7005.

©ASCO/Todd Buchanan 2018

CHICAGO—Cord blood (CB) is a viable source of natural killer (NK) cells for adoptive cellular therapy for multiple myeloma (MM), according to a speaker at the 2018 ASCO Annual Meeting.

Ex-vivo expanded cord blood NK cells were well tolerated without significant graft-versus-host disease (GVHD) or cytokine release syndrome (CRS) in a phase 2 study.

Nina Shah, MD, of the University of California San Francisco, reported these results as abstract 8006.*

The phase 2 study (NCT01729091) included 33 patients with symptomatic MM who were appropriate candidates for autologous stem cell transplant (ASCT).

For each patient, investigators chose cord blood units with at least a 4/6 match at HLA-A, -B and –DR.

Prior to the autologous graft, patients received lenalidomide and melphalan. Lenalidomide was given based on preclinical data suggesting synergy between that immunomodulatory agent and NK cells, Dr Shah said.

Patients were a median age of 59 (range, 25 – 72), 36% had a history of progressive disease or relapse, and 73% had adverse cytogenetics/FISH, were ISS III, or had a history of progressive disease or relapse.

Results

Dr Shah observed that in a generally high-risk population, responses to treatment with cord blood NK cells in the setting of ASCT were “encouraging,” with 79% of patients achieving very good partial response (VGPR) or better.

Twenty-one patients (64%) achieved a complete response (CR) or near CR. And 61% achieved minimal residual disease (MRD) negativity by day 100.

Patients had an estimated 3-year progression-free survival of 52%.

Three patients died, all from disease progression, and 13 patients have progressed.

The investigators observed no infusional toxicities, no GVHD, no CRS, and no neurotoxicity.

One patient experienced graft failure and was rescued with an autologous back-up graft.

"We are able to detect the donor-derived NK cells up to 13 days after infusion,” Dr Shah said, “but I think a more sensitive analysis with flow chimerism will not only allow us to detect more patients, but also better interrogate them to truly understand the in vivo phenotype and activation status of these cells."

Dr Shah indicated she and her colleagues became interested in studying cord blood for NK cell therapy because it is a known source of hematopoietic cells that is immediately available, does not require donor manipulation, and has more flexibility in genetic matching.

Previously, Dr Shah and colleagues conducted a phase 1 study, in which 12 patients received cord blood NK cells up to a dose of 1 x 10⁸ NK cells/kg. “This was determined to be adequate and safe to move on to the phase 2,” she said.

Despite encouraging results, more research needs to be done, according to Dr Shah. “I don't think this is the end-all, be-all for NK cell therapy.”

Some future directions include combination with antibody therapy, improving NK persistence in vivo using cytokine manipulation, and possibly engineering chimeric antigen receptor (CAR)-modified NK cells, Dr Shah observed.

It’s also possible that HLA match may not be needed: “If that is the case, we will truly have an off-the-shelf source of NK cells that we can apply more readily to various patients,” she said.

The study was supported by Celgene Corporation, Stading-Younger Cancer Research Foundation, and the MD Anderson High-Risk Multiple Myeloma Moonshot Project.  

*Data in the presentation differ from the abstract.

©ASCO/Todd Buchanan 2018

CHICAGO—Cord blood (CB) is a viable source of natural killer (NK) cells for adoptive cellular therapy for multiple myeloma (MM), according to a speaker at the 2018 ASCO Annual Meeting.

Ex-vivo expanded cord blood NK cells were well tolerated without significant graft-versus-host disease (GVHD) or cytokine release syndrome (CRS) in a phase 2 study.

Nina Shah, MD, of the University of California San Francisco, reported these results as abstract 8006.*

The phase 2 study (NCT01729091) included 33 patients with symptomatic MM who were appropriate candidates for autologous stem cell transplant (ASCT).

For each patient, investigators chose cord blood units with at least a 4/6 match at HLA-A, -B and –DR.

Prior to the autologous graft, patients received lenalidomide and melphalan. Lenalidomide was given based on preclinical data suggesting synergy between that immunomodulatory agent and NK cells, Dr Shah said.

Patients were a median age of 59 (range, 25 – 72), 36% had a history of progressive disease or relapse, and 73% had adverse cytogenetics/FISH, were ISS III, or had a history of progressive disease or relapse.

Results

Dr Shah observed that in a generally high-risk population, responses to treatment with cord blood NK cells in the setting of ASCT were “encouraging,” with 79% of patients achieving very good partial response (VGPR) or better.

Twenty-one patients (64%) achieved a complete response (CR) or near CR. And 61% achieved minimal residual disease (MRD) negativity by day 100.

Patients had an estimated 3-year progression-free survival of 52%.

Three patients died, all from disease progression, and 13 patients have progressed.

The investigators observed no infusional toxicities, no GVHD, no CRS, and no neurotoxicity.

One patient experienced graft failure and was rescued with an autologous back-up graft.

"We are able to detect the donor-derived NK cells up to 13 days after infusion,” Dr Shah said, “but I think a more sensitive analysis with flow chimerism will not only allow us to detect more patients, but also better interrogate them to truly understand the in vivo phenotype and activation status of these cells."

Dr Shah indicated she and her colleagues became interested in studying cord blood for NK cell therapy because it is a known source of hematopoietic cells that is immediately available, does not require donor manipulation, and has more flexibility in genetic matching.

Previously, Dr Shah and colleagues conducted a phase 1 study, in which 12 patients received cord blood NK cells up to a dose of 1 x 10⁸ NK cells/kg. “This was determined to be adequate and safe to move on to the phase 2,” she said.

Despite encouraging results, more research needs to be done, according to Dr Shah. “I don't think this is the end-all, be-all for NK cell therapy.”

Some future directions include combination with antibody therapy, improving NK persistence in vivo using cytokine manipulation, and possibly engineering chimeric antigen receptor (CAR)-modified NK cells, Dr Shah observed.

It’s also possible that HLA match may not be needed: “If that is the case, we will truly have an off-the-shelf source of NK cells that we can apply more readily to various patients,” she said.

The study was supported by Celgene Corporation, Stading-Younger Cancer Research Foundation, and the MD Anderson High-Risk Multiple Myeloma Moonshot Project.  

*Data in the presentation differ from the abstract.

©ASCO/Todd Buchanan 2018

CHICAGO—Cord blood (CB) is a viable source of natural killer (NK) cells for adoptive cellular therapy for multiple myeloma (MM), according to a speaker at the 2018 ASCO Annual Meeting.

Ex-vivo expanded cord blood NK cells were well tolerated without significant graft-versus-host disease (GVHD) or cytokine release syndrome (CRS) in a phase 2 study.

Nina Shah, MD, of the University of California San Francisco, reported these results as abstract 8006.*

The phase 2 study (NCT01729091) included 33 patients with symptomatic MM who were appropriate candidates for autologous stem cell transplant (ASCT).

For each patient, investigators chose cord blood units with at least a 4/6 match at HLA-A, -B and –DR.

Prior to the autologous graft, patients received lenalidomide and melphalan. Lenalidomide was given based on preclinical data suggesting synergy between that immunomodulatory agent and NK cells, Dr Shah said.

Patients were a median age of 59 (range, 25 – 72), 36% had a history of progressive disease or relapse, and 73% had adverse cytogenetics/FISH, were ISS III, or had a history of progressive disease or relapse.

Results

Dr Shah observed that in a generally high-risk population, responses to treatment with cord blood NK cells in the setting of ASCT were “encouraging,” with 79% of patients achieving very good partial response (VGPR) or better.

Twenty-one patients (64%) achieved a complete response (CR) or near CR. And 61% achieved minimal residual disease (MRD) negativity by day 100.

Patients had an estimated 3-year progression-free survival of 52%.

Three patients died, all from disease progression, and 13 patients have progressed.

The investigators observed no infusional toxicities, no GVHD, no CRS, and no neurotoxicity.

One patient experienced graft failure and was rescued with an autologous back-up graft.

"We are able to detect the donor-derived NK cells up to 13 days after infusion,” Dr Shah said, “but I think a more sensitive analysis with flow chimerism will not only allow us to detect more patients, but also better interrogate them to truly understand the in vivo phenotype and activation status of these cells."

Dr Shah indicated she and her colleagues became interested in studying cord blood for NK cell therapy because it is a known source of hematopoietic cells that is immediately available, does not require donor manipulation, and has more flexibility in genetic matching.

Previously, Dr Shah and colleagues conducted a phase 1 study, in which 12 patients received cord blood NK cells up to a dose of 1 x 10⁸ NK cells/kg. “This was determined to be adequate and safe to move on to the phase 2,” she said.

Despite encouraging results, more research needs to be done, according to Dr Shah. “I don't think this is the end-all, be-all for NK cell therapy.”

Some future directions include combination with antibody therapy, improving NK persistence in vivo using cytokine manipulation, and possibly engineering chimeric antigen receptor (CAR)-modified NK cells, Dr Shah observed.

It’s also possible that HLA match may not be needed: “If that is the case, we will truly have an off-the-shelf source of NK cells that we can apply more readily to various patients,” she said.

The study was supported by Celgene Corporation, Stading-Younger Cancer Research Foundation, and the MD Anderson High-Risk Multiple Myeloma Moonshot Project.  

*Data in the presentation differ from the abstract.

The American Cancer Society recommends all U.S. adults at average risk of colorectal cancer (CRC) undergo screening starting at age 45 years.

That update to ACS recommendations is based on an increasing burden of CRC in younger individuals, microsimulation modeling results, and a “reasonable expectation” that screening tests will perform as well in adults aged 45-49 years as they do in older adults, members of the ACS Guideline Development Group said in the guideline, which was published in CA: A Cancer Journal for Clinicians.

Starting screening at age 45 contrasts with recommendations from the U.S. Preventive Services Task Force (USPSTF), which in 2016 gave an “A” recommendation for CRC screening from 50 to 75 years of age. At the time, the USPSTF noted a modest increase in life-years gained by starting earlier, based on microsimulation modeling. But it concluded that available evidence best supported starting at age 50.

The updated ACS guidelines are based in part on a modeling study that the authors say extends the previous analysis conducted for the USPSTF.

“The recommendation places a high value on the potential years of life saved, addresses anticipated rising incidence going forward, and is expected to contribute to the reduction in disparities in incidence before age 50 years in some racial groups,” the ACS guideline authors added.

The recommendation to start screening at age 45 is a “qualified” recommendation, the authors said, given the limitations of the current evidence base. Most studies to date have been focused on older individuals, in keeping with long-standing recommendations to start screening at age 50.

The move downward in screening age recommendation acknowledges one of the most “significant and disturbing” developments in CRC, the guideline’s authors said: the marked increase in incidence among younger individuals.

While CRC incidence and mortality have been declining in adults aged 55 years and older, recent studies cited in the ACS guideline document show a 51% increase in incidence from 1994 to 2014 – and an 11% increase in mortality from 2005 to 2015 – for adults younger than 55 years.

The current age-specific incidence rate for adults 45-49 years is 31.4 per 100,000, compared with 58.4 per 100,000 in adults 50-54 years. However, the ACS guideline authors said the higher rate in the older cohort is partly influenced by more frequent screening. “The true underlying risk in adults aged 45-49 years is likely closer to the risk in adults aged 50-54 years than the most recent age-specific rates would suggest,” they wrote.

Since patients in this age range have not been routinely screened before, the ACS recommendation is based on modeling. Now we need to analyze the outcomes of early screening to identify which patients will benefit most. Choices for screening include either a structural examination or a high-sensitivity stool-based test, according to the guideline, which doesn’t state a preference for any particular test.

The AGA, in their statement in response, noted that with CRC rates rising in people younger than age 50, it is appropriate to consider beginning routine screening at age 45. The statement continues “Since patients in this age range have not been previously routinely screened, the ACS recommendation is based on modeling. Now we need to analyze the outcomes of early screening to identify which patients will benefit most.”

In addition to Dr. Wolf, members of the ACS Guideline Development Group received no compensation.

SOURCE: Wolf AMD et al. CA Cancer J Clin. 2018 May 30. doi: 10.3322/caac.21457.

The American Cancer Society recommends all U.S. adults at average risk of colorectal cancer (CRC) undergo screening starting at age 45 years.

That update to ACS recommendations is based on an increasing burden of CRC in younger individuals, microsimulation modeling results, and a “reasonable expectation” that screening tests will perform as well in adults aged 45-49 years as they do in older adults, members of the ACS Guideline Development Group said in the guideline, which was published in CA: A Cancer Journal for Clinicians.

Starting screening at age 45 contrasts with recommendations from the U.S. Preventive Services Task Force (USPSTF), which in 2016 gave an “A” recommendation for CRC screening from 50 to 75 years of age. At the time, the USPSTF noted a modest increase in life-years gained by starting earlier, based on microsimulation modeling. But it concluded that available evidence best supported starting at age 50.

The updated ACS guidelines are based in part on a modeling study that the authors say extends the previous analysis conducted for the USPSTF.

“The recommendation places a high value on the potential years of life saved, addresses anticipated rising incidence going forward, and is expected to contribute to the reduction in disparities in incidence before age 50 years in some racial groups,” the ACS guideline authors added.

The recommendation to start screening at age 45 is a “qualified” recommendation, the authors said, given the limitations of the current evidence base. Most studies to date have been focused on older individuals, in keeping with long-standing recommendations to start screening at age 50.

The move downward in screening age recommendation acknowledges one of the most “significant and disturbing” developments in CRC, the guideline’s authors said: the marked increase in incidence among younger individuals.

While CRC incidence and mortality have been declining in adults aged 55 years and older, recent studies cited in the ACS guideline document show a 51% increase in incidence from 1994 to 2014 – and an 11% increase in mortality from 2005 to 2015 – for adults younger than 55 years.

The current age-specific incidence rate for adults 45-49 years is 31.4 per 100,000, compared with 58.4 per 100,000 in adults 50-54 years. However, the ACS guideline authors said the higher rate in the older cohort is partly influenced by more frequent screening. “The true underlying risk in adults aged 45-49 years is likely closer to the risk in adults aged 50-54 years than the most recent age-specific rates would suggest,” they wrote.

Since patients in this age range have not been routinely screened before, the ACS recommendation is based on modeling. Now we need to analyze the outcomes of early screening to identify which patients will benefit most. Choices for screening include either a structural examination or a high-sensitivity stool-based test, according to the guideline, which doesn’t state a preference for any particular test.

The AGA, in their statement in response, noted that with CRC rates rising in people younger than age 50, it is appropriate to consider beginning routine screening at age 45. The statement continues “Since patients in this age range have not been previously routinely screened, the ACS recommendation is based on modeling. Now we need to analyze the outcomes of early screening to identify which patients will benefit most.”

In addition to Dr. Wolf, members of the ACS Guideline Development Group received no compensation.

SOURCE: Wolf AMD et al. CA Cancer J Clin. 2018 May 30. doi: 10.3322/caac.21457.

The American Cancer Society recommends all U.S. adults at average risk of colorectal cancer (CRC) undergo screening starting at age 45 years.

That update to ACS recommendations is based on an increasing burden of CRC in younger individuals, microsimulation modeling results, and a “reasonable expectation” that screening tests will perform as well in adults aged 45-49 years as they do in older adults, members of the ACS Guideline Development Group said in the guideline, which was published in CA: A Cancer Journal for Clinicians.

Starting screening at age 45 contrasts with recommendations from the U.S. Preventive Services Task Force (USPSTF), which in 2016 gave an “A” recommendation for CRC screening from 50 to 75 years of age. At the time, the USPSTF noted a modest increase in life-years gained by starting earlier, based on microsimulation modeling. But it concluded that available evidence best supported starting at age 50.

The updated ACS guidelines are based in part on a modeling study that the authors say extends the previous analysis conducted for the USPSTF.

“The recommendation places a high value on the potential years of life saved, addresses anticipated rising incidence going forward, and is expected to contribute to the reduction in disparities in incidence before age 50 years in some racial groups,” the ACS guideline authors added.

The recommendation to start screening at age 45 is a “qualified” recommendation, the authors said, given the limitations of the current evidence base. Most studies to date have been focused on older individuals, in keeping with long-standing recommendations to start screening at age 50.

The move downward in screening age recommendation acknowledges one of the most “significant and disturbing” developments in CRC, the guideline’s authors said: the marked increase in incidence among younger individuals.

While CRC incidence and mortality have been declining in adults aged 55 years and older, recent studies cited in the ACS guideline document show a 51% increase in incidence from 1994 to 2014 – and an 11% increase in mortality from 2005 to 2015 – for adults younger than 55 years.

The current age-specific incidence rate for adults 45-49 years is 31.4 per 100,000, compared with 58.4 per 100,000 in adults 50-54 years. However, the ACS guideline authors said the higher rate in the older cohort is partly influenced by more frequent screening. “The true underlying risk in adults aged 45-49 years is likely closer to the risk in adults aged 50-54 years than the most recent age-specific rates would suggest,” they wrote.

Since patients in this age range have not been routinely screened before, the ACS recommendation is based on modeling. Now we need to analyze the outcomes of early screening to identify which patients will benefit most. Choices for screening include either a structural examination or a high-sensitivity stool-based test, according to the guideline, which doesn’t state a preference for any particular test.

The AGA, in their statement in response, noted that with CRC rates rising in people younger than age 50, it is appropriate to consider beginning routine screening at age 45. The statement continues “Since patients in this age range have not been previously routinely screened, the ACS recommendation is based on modeling. Now we need to analyze the outcomes of early screening to identify which patients will benefit most.”

In addition to Dr. Wolf, members of the ACS Guideline Development Group received no compensation.

SOURCE: Wolf AMD et al. CA Cancer J Clin. 2018 May 30. doi: 10.3322/caac.21457.

CHICAGO – Denosumab may be preferable to bisphosphonates in myeloma patients in specific scenarios, G. David Roodman, MD, PhD, reported at the annual meeting of the American Society of Clinical Oncology.

“We use denosumab in patients with compromised renal function,” said Dr. Roodman, director of the Division of Hematology-Oncology at Indiana University, Indianapolis, noting one such scenario. That use of denosumab echoes recently published ASCO guidelines on bone-modifying therapy.

Andrew D. Bowser/MDedge News

The addition of denosumab was based in part on results of a recent randomized phase 3 trial that comprised 1,718 myeloma patients who were treated with either denosumab or zoledronic acid.

The primary endpoint, time to first on-study skeletal-related event, was evaluated after 676 skeletal-related events had accrued on study. The investigators found no difference in time to first event (hazard ratio [HR], 0.98; 95% confidence interval, 0.85-1.14; P = 0.82).

Likewise, the secondary endpoint of overall survival showed no difference between arms (HR, 0.90; 95% CI, 0.70-1.16), though an exploratory analysis did suggest denosumab was superior on the endpoint of progression-free survival (HR, 0.82; 95% CI, 0.68-0.99).

The ASCO guidelines also recommend that clinicians consider less-frequent dosing in patients with responsive or stable disease. That recommendation is based on results of two studies of less-frequent dosing prompted by concerns over the risk of osteonecrosis of the jaw, an uncommon but potentially serious complication associated with bone-modifying agents.

Both studies suggested every-3-months dosing of zoledronic acid could be effective. However, Dr. Roodman noted that both studies had limitations that need to be considered, including small numbers of myeloma patients, limited duration of therapy studied, and a high dropout rate in the case of one study. Due to those limitations, “it’s very difficult to draw conclusions about this today,” Dr. Roodman said.

Dr. Roodman reported that he had a consulting or advisory role with Amgen.

CHICAGO – Denosumab may be preferable to bisphosphonates in myeloma patients in specific scenarios, G. David Roodman, MD, PhD, reported at the annual meeting of the American Society of Clinical Oncology.

“We use denosumab in patients with compromised renal function,” said Dr. Roodman, director of the Division of Hematology-Oncology at Indiana University, Indianapolis, noting one such scenario. That use of denosumab echoes recently published ASCO guidelines on bone-modifying therapy.

Andrew D. Bowser/MDedge News

The addition of denosumab was based in part on results of a recent randomized phase 3 trial that comprised 1,718 myeloma patients who were treated with either denosumab or zoledronic acid.

The primary endpoint, time to first on-study skeletal-related event, was evaluated after 676 skeletal-related events had accrued on study. The investigators found no difference in time to first event (hazard ratio [HR], 0.98; 95% confidence interval, 0.85-1.14; P = 0.82).

Likewise, the secondary endpoint of overall survival showed no difference between arms (HR, 0.90; 95% CI, 0.70-1.16), though an exploratory analysis did suggest denosumab was superior on the endpoint of progression-free survival (HR, 0.82; 95% CI, 0.68-0.99).

The ASCO guidelines also recommend that clinicians consider less-frequent dosing in patients with responsive or stable disease. That recommendation is based on results of two studies of less-frequent dosing prompted by concerns over the risk of osteonecrosis of the jaw, an uncommon but potentially serious complication associated with bone-modifying agents.

Both studies suggested every-3-months dosing of zoledronic acid could be effective. However, Dr. Roodman noted that both studies had limitations that need to be considered, including small numbers of myeloma patients, limited duration of therapy studied, and a high dropout rate in the case of one study. Due to those limitations, “it’s very difficult to draw conclusions about this today,” Dr. Roodman said.

Dr. Roodman reported that he had a consulting or advisory role with Amgen.

CHICAGO – Denosumab may be preferable to bisphosphonates in myeloma patients in specific scenarios, G. David Roodman, MD, PhD, reported at the annual meeting of the American Society of Clinical Oncology.

“We use denosumab in patients with compromised renal function,” said Dr. Roodman, director of the Division of Hematology-Oncology at Indiana University, Indianapolis, noting one such scenario. That use of denosumab echoes recently published ASCO guidelines on bone-modifying therapy.

Andrew D. Bowser/MDedge News

The addition of denosumab was based in part on results of a recent randomized phase 3 trial that comprised 1,718 myeloma patients who were treated with either denosumab or zoledronic acid.

The primary endpoint, time to first on-study skeletal-related event, was evaluated after 676 skeletal-related events had accrued on study. The investigators found no difference in time to first event (hazard ratio [HR], 0.98; 95% confidence interval, 0.85-1.14; P = 0.82).

Likewise, the secondary endpoint of overall survival showed no difference between arms (HR, 0.90; 95% CI, 0.70-1.16), though an exploratory analysis did suggest denosumab was superior on the endpoint of progression-free survival (HR, 0.82; 95% CI, 0.68-0.99).

The ASCO guidelines also recommend that clinicians consider less-frequent dosing in patients with responsive or stable disease. That recommendation is based on results of two studies of less-frequent dosing prompted by concerns over the risk of osteonecrosis of the jaw, an uncommon but potentially serious complication associated with bone-modifying agents.

Both studies suggested every-3-months dosing of zoledronic acid could be effective. However, Dr. Roodman noted that both studies had limitations that need to be considered, including small numbers of myeloma patients, limited duration of therapy studied, and a high dropout rate in the case of one study. Due to those limitations, “it’s very difficult to draw conclusions about this today,” Dr. Roodman said.

Dr. Roodman reported that he had a consulting or advisory role with Amgen.

CHICAGO – The JAK 1/2 inhibitor ruxolitinib (Jakafi), in combination with lenalidomide and methylprednisolone, overcame resistance to lenalidomide in about half of 28 heavily pre-treated patients with relapsed/refractory multiple myeloma, based on phase I trial results presented at the annual meeting of the American Society of Clinical Oncology (ASCO).

The clinical trial is the first to demonstrate the activity of a JAK inhibitor in the treatment of myeloma patients, according to investigator James R. Berenson, MD, medical and scientific director for the Institute for Myeloma & Bone Cancer Research (IMBCR), West Hollywood, Calif.

Andrew Bowser/MDedge News

These results are encouraging, though challenges remain, said Craig Hofmeister, MD, MPH, of Winship Cancer Institute, Emory University, Atlanta.

“Clearly in these patients who are 100% lenalidomide refractory, the overall response rate of anything greater than or close to 20, 30, 40% is very appealing,” Dr. Hofmeister said in an ASCO presentation discussing the results of this trial.

The usual rationale for JAK inhibition is targeting of the bone microenvironment, but the microenvironment is a formidable opponent, Dr. Hofmeister said in his presentation.

“That’s an uphill battle,” he said. “There is an upcoming carfilzomib and ruxolitinib trial in multiple myeloma moving forward, and I’d be excited to see” the results.

The study (NCT03110822) was sponsored by Oncotherapeutics in collaboration with Incyte, the maker of ruxolitinib (Jakafi). Dr. Berenson, the presenting author, had disclosures related to Incyte, as well as Amgen, Bristol-Myers Squibb, Celgene, Janssen, Takeda, and OncoTracker.

SOURCE: Berenson JR, et al. J Clin Oncol 36, 2018 (suppl; abstr 8005).

CHICAGO – The JAK 1/2 inhibitor ruxolitinib (Jakafi), in combination with lenalidomide and methylprednisolone, overcame resistance to lenalidomide in about half of 28 heavily pre-treated patients with relapsed/refractory multiple myeloma, based on phase I trial results presented at the annual meeting of the American Society of Clinical Oncology (ASCO).

The clinical trial is the first to demonstrate the activity of a JAK inhibitor in the treatment of myeloma patients, according to investigator James R. Berenson, MD, medical and scientific director for the Institute for Myeloma & Bone Cancer Research (IMBCR), West Hollywood, Calif.

Andrew Bowser/MDedge News

These results are encouraging, though challenges remain, said Craig Hofmeister, MD, MPH, of Winship Cancer Institute, Emory University, Atlanta.

“Clearly in these patients who are 100% lenalidomide refractory, the overall response rate of anything greater than or close to 20, 30, 40% is very appealing,” Dr. Hofmeister said in an ASCO presentation discussing the results of this trial.

The usual rationale for JAK inhibition is targeting of the bone microenvironment, but the microenvironment is a formidable opponent, Dr. Hofmeister said in his presentation.

“That’s an uphill battle,” he said. “There is an upcoming carfilzomib and ruxolitinib trial in multiple myeloma moving forward, and I’d be excited to see” the results.

The study (NCT03110822) was sponsored by Oncotherapeutics in collaboration with Incyte, the maker of ruxolitinib (Jakafi). Dr. Berenson, the presenting author, had disclosures related to Incyte, as well as Amgen, Bristol-Myers Squibb, Celgene, Janssen, Takeda, and OncoTracker.

SOURCE: Berenson JR, et al. J Clin Oncol 36, 2018 (suppl; abstr 8005).

CHICAGO – The JAK 1/2 inhibitor ruxolitinib (Jakafi), in combination with lenalidomide and methylprednisolone, overcame resistance to lenalidomide in about half of 28 heavily pre-treated patients with relapsed/refractory multiple myeloma, based on phase I trial results presented at the annual meeting of the American Society of Clinical Oncology (ASCO).

The clinical trial is the first to demonstrate the activity of a JAK inhibitor in the treatment of myeloma patients, according to investigator James R. Berenson, MD, medical and scientific director for the Institute for Myeloma & Bone Cancer Research (IMBCR), West Hollywood, Calif.

Andrew Bowser/MDedge News

These results are encouraging, though challenges remain, said Craig Hofmeister, MD, MPH, of Winship Cancer Institute, Emory University, Atlanta.

“Clearly in these patients who are 100% lenalidomide refractory, the overall response rate of anything greater than or close to 20, 30, 40% is very appealing,” Dr. Hofmeister said in an ASCO presentation discussing the results of this trial.

The usual rationale for JAK inhibition is targeting of the bone microenvironment, but the microenvironment is a formidable opponent, Dr. Hofmeister said in his presentation.

“That’s an uphill battle,” he said. “There is an upcoming carfilzomib and ruxolitinib trial in multiple myeloma moving forward, and I’d be excited to see” the results.

The study (NCT03110822) was sponsored by Oncotherapeutics in collaboration with Incyte, the maker of ruxolitinib (Jakafi). Dr. Berenson, the presenting author, had disclosures related to Incyte, as well as Amgen, Bristol-Myers Squibb, Celgene, Janssen, Takeda, and OncoTracker.

SOURCE: Berenson JR, et al. J Clin Oncol 36, 2018 (suppl; abstr 8005).