TY - JOUR
T1 - Venetoclax-rituximab with or without bendamustine vs bendamustine-rituximab in relapsed/refractory follicular lymphoma
AU - Zinzani, Pier Luigi
AU - Flinn, Ian W.
AU - Yuen, Sam L.S.
AU - Topp, Max S.
AU - Rusconi, Chiara
AU - Fleury, Isabelle
AU - Le Dû, Katell
AU - Arthur, Christopher
AU - Pro, Barbara
AU - Gritti, Giuseppe
AU - Crump, Michael
AU - Petrich, Adam
AU - Samineni, Divya
AU - Sinha, Arijit
AU - Punnoose, Elizabeth A.
AU - Szafer-Glusman, Edith
AU - Spielewoy, Nathalie
AU - Mobasher, Mehrdad
AU - Humphrey, Kathryn
AU - Kornacker, Martin
AU - Hiddemann, Wolfgang
N1 - Funding Information:
Genentech and AbbVie provided financial support for the study and participated in the design, study conduct, analysis, and interpretation of data, as well as the writing, review, and approval of the presentation. Medical writing support was provided by Catherine Amey and Kate Rijnen of Gardiner-Caldwell Communications, Macclesfield, UK, and was funded by F. Hoffmann-La Roche Ltd.
Funding Information:
Special thanks to the patients and their families, INVs, study coordinators and support staff, and Genentech CONTRALTO study team members. Venetoclax is being developed in collaboration between Genentech and AbbVie. Genentech and AbbVie provided financial support for the study and participated in the design, study conduct, analysis, and interpretation of data, as well as the writing, review, and approval of the presentation. Medical writing support was provided by Catherine Amey and Kate Rijnen of Gardiner-Caldwell Communications, Macclesfield, UK, and was funded by F. Hoffmann-La Roche Ltd.
Publisher Copyright:
© 2020 American Society of Hematology
PY - 2020/12/3
Y1 - 2020/12/3
N2 - This open-label phase 2 study (CONTRALTO) assessed the safety and efficacy of BCL-2 inhibitor venetoclax (VEN) plus rituximab (R), and VEN plus bendamustine (B) and R, vs B + R (BR) alone in relapsed/refractory (R/R) follicular lymphoma. Patients in the chemotherapy-free arm (arm A: VEN + R) received VEN 800 mg/d plus R 375 mg/m2 on days 1, 8, 15, and 22 of cycle 1 and day 1 of cycles 4, 6, 8, 10, and 12. After a safety run-in with VEN 600 mg, patients in the chemotherapy-containing cohort were randomized to either VEN + BR (arm B; VEN 800 mg/d for 1 year + 6 cycles of BR [B 90 mg/m2 on days 1 and 2 and R 375 mg/m2 on day 1]) or 6 cycles of BR (arm C). Overall, 163 patients were analyzed (9 in the safety run-in and 52, 51, and 51 in arms A, B, and C, respectively). Complete metabolic/complete response rates were 17% (arm A), 75% (arm B), and 69% (arm C). Of patients in arm B, only 61% received ≥90% of the planned B dose vs 96% of patients in arm C. More frequent hematologic toxicity resulted in more reduced dosing/treatment discontinuation in arm B vs arm C. Rates of grade 3/4 adverse events were 51.9%, 93.9%, and 60.0% in arms A, B, and C, respectively. VEN + BR led to increased toxicity and lower dose intensity of BR than in arm C, but efficacy was similar. Optimizing dose and schedule to maintain BR dose intensity may improve efficacy and tolerability of VEN + BR, while VEN + R data warrant further study. This study was registered at www.clinicaltrials.gov as #NCT02187861. Key Points: • Chemotherapy-free VEN + R had modest efficacy and acceptable toxicity in relapsed/refractory disease warranting further study. • VEN + BR led to increased toxicity; optimized chemotherapeutic dosing and/or combinations remain to be explored.
AB - This open-label phase 2 study (CONTRALTO) assessed the safety and efficacy of BCL-2 inhibitor venetoclax (VEN) plus rituximab (R), and VEN plus bendamustine (B) and R, vs B + R (BR) alone in relapsed/refractory (R/R) follicular lymphoma. Patients in the chemotherapy-free arm (arm A: VEN + R) received VEN 800 mg/d plus R 375 mg/m2 on days 1, 8, 15, and 22 of cycle 1 and day 1 of cycles 4, 6, 8, 10, and 12. After a safety run-in with VEN 600 mg, patients in the chemotherapy-containing cohort were randomized to either VEN + BR (arm B; VEN 800 mg/d for 1 year + 6 cycles of BR [B 90 mg/m2 on days 1 and 2 and R 375 mg/m2 on day 1]) or 6 cycles of BR (arm C). Overall, 163 patients were analyzed (9 in the safety run-in and 52, 51, and 51 in arms A, B, and C, respectively). Complete metabolic/complete response rates were 17% (arm A), 75% (arm B), and 69% (arm C). Of patients in arm B, only 61% received ≥90% of the planned B dose vs 96% of patients in arm C. More frequent hematologic toxicity resulted in more reduced dosing/treatment discontinuation in arm B vs arm C. Rates of grade 3/4 adverse events were 51.9%, 93.9%, and 60.0% in arms A, B, and C, respectively. VEN + BR led to increased toxicity and lower dose intensity of BR than in arm C, but efficacy was similar. Optimizing dose and schedule to maintain BR dose intensity may improve efficacy and tolerability of VEN + BR, while VEN + R data warrant further study. This study was registered at www.clinicaltrials.gov as #NCT02187861. Key Points: • Chemotherapy-free VEN + R had modest efficacy and acceptable toxicity in relapsed/refractory disease warranting further study. • VEN + BR led to increased toxicity; optimized chemotherapeutic dosing and/or combinations remain to be explored.
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U2 - 10.1182/blood.2020005588
DO - 10.1182/blood.2020005588
M3 - Article
C2 - 32785666
AN - SCOPUS:85097210540
SN - 0006-4971
VL - 136
SP - 2628
EP - 2637
JO - Blood
JF - Blood
IS - 23
ER -