venetoclax

Venetoclax-Rituximab with or without Bendamustine vs Bendamustine-Rituximab in Relapsed/Refractory Follicular Lymphoma

Venetoclax-Rituximab with or without Bendamustine vs Bendamustine-Rituximab in Relapsed/Refractory Follicular Lymphoma

On December 23, 2020, investigators reported in the journal Blood, the results of the open label phase 2 CONTRALTO trial.  The purpose of the study was to assess the safety and efficacy of the BCL-2 inhibitor venetoclax plus rituximab as well as venetoclax plus bendamustine and rituximab versus bendamustine and rituximab alone in relapsed / refractory follicular lymphoma. 

Patients in the chemotherapy free arm, called Arm A, were treated with venetoclax and rituximab at 800 mg/day plus 375 mg/m² on days 1 8, 8, 15 and 22 of cycle 1 day 1 of cycle 4, 6, 8, 10 and cycle 12 for V and R respectively.  After a safety run in with 600 mg of venetoclax, patients who were in the chemotherapy cohort were randomized to either venetoclax plus bendamustine plus rituximab, arm B, venetoclax 800 mg/day for 1 year +6 cycles of bendamustine plus rituximab, 90 mg/m² on day 1 and day 2 and 375 mg/m² on day 1, for bendamustine and rituximab respectively for 6 cycles of bendamustine plus rituximab, respectively.

163 patients were analyzed, 9 in the safety run-in as well as 52, 51 and 51 in arms A, B and C respectively.  The complete metabolic and complete response rates were 17% for arm A, 75% for arm B and 69% for arm C.  For patients on arm B, only 61% received 90% or more of the planned bendamustine dose, versus 96% in arm C.  There were notably more frequent hematologic toxicities, resulting in more reduced dosing and treatment discontinuation in arm B versus arm C.  Grade 3 and 4 adverse events, were seen in 51.9%, 93.9% and 60% in arms A, B and arm C respectively.  That venetoclax / bendamustine / rituximab combo led to increased toxicity and a lower dose intensity of bendamustine / rituximab compared to arm C, but had similar efficacy.  Optimizing dosing scheduling to maintain bendamustine / rituximab dose intensity could potentially improve the efficacy and tolerability of the triplet combination while venetoclax / rituximab data warrant further study for the investigators.

https://ashpublications.org/Blood/article/136/23/2628/461787/Venetoclax-rituximab-with-or-without-bendamustine

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