TY - JOUR
T1 - A three-arm randomized Phase II study of bendamustine/rituximab with bortezomib induction or lenalidomide continuation in untreated follicular lymphoma
T2 - ECOG-ACRIN E2408
AU - Evens, Andrew M.
AU - Hong, Fangxin
AU - Habermann, Thomas M.
AU - Advani, Ranjana H.
AU - Gascoyne, Randy D.
AU - Witzig, Thomas E.
AU - Quon, Andrew
AU - Ranheim, Erik A.
AU - Ansell, Stephen M.
AU - Cheema, Puneet Singh
AU - Dy, Philip A.
AU - O'Brien, Timothy E.
AU - Winter, Jane N.
AU - Cescon, Terrence P.
AU - Chang, Julie E.
AU - Kahl, Brad S.
N1 - Publisher Copyright:
© 2020 American Association for Cancer Research.
PY - 2020/9
Y1 - 2020/9
N2 - Purpose: We sought to improve upon frontline bendamustine/ rituximab (BR) induction therapy followed by rituximab maintenance in untreated high-risk follicular lymphoma (FL). Patients and Methods: Patients were randomized to BR induction followed by 2-year rituximab maintenance (BR-R), BR with bortezomib and rituximab maintenance (BVR-R), or BR followed by lenalidomide (1 year) with rituximab maintenance (BR-LR). Dual primary objectives were complete remission (CR) rate and 1-year disease-free survival (DFS); 289 patients enrolled (NCT01216683). Results: For induction, 92%, 87%, and 86% of patients randomized to BR-R, BVR-R, or BR-LR received six cycles, respectively. CR rate with BR versus BVR induction was 62% versus 75%, respectively (P ¼ 0.04). One-year DFS rates with BR-R versus BR-LR were 85% versus 67%, respectively (P ¼ 0.0009). This was due to an imbalance in CR rates post-BR induction and discontinuation due to adverse events (AEs). The most common grade 3-4 AEs for BVR versus BR were neutropenia and sensory neuropathy (12% vs <1%); 83% of the latter occurred with intravenous bortezomib. The most common grade 3-4 AEs related to LR versus rituximab maintenance were neutropenia 66% versus 21%, respectively (P < 0.0001), and febrile neutropenia 10% versus 2%, respectively (P ¼ 0.05). The overall treatment-related mortality was 1.4%. With 5-year median follow-up, 3-year PFS rates for BR-R, BVR-R, and BR-LR were 77%, 82%, and 76%, respectively (P ¼ 0.36) with OS rates of 87%, 90%, and 84%, respectively (P ¼ 0.79). For prognostication, CR rate and POD-24 were associated with survival. Conclusions: Altogether, neither bortezomib added to BR induction nor lenalidomide added to rituximab maintenance immediately post-BR induction is recommended in untreated FL.
AB - Purpose: We sought to improve upon frontline bendamustine/ rituximab (BR) induction therapy followed by rituximab maintenance in untreated high-risk follicular lymphoma (FL). Patients and Methods: Patients were randomized to BR induction followed by 2-year rituximab maintenance (BR-R), BR with bortezomib and rituximab maintenance (BVR-R), or BR followed by lenalidomide (1 year) with rituximab maintenance (BR-LR). Dual primary objectives were complete remission (CR) rate and 1-year disease-free survival (DFS); 289 patients enrolled (NCT01216683). Results: For induction, 92%, 87%, and 86% of patients randomized to BR-R, BVR-R, or BR-LR received six cycles, respectively. CR rate with BR versus BVR induction was 62% versus 75%, respectively (P ¼ 0.04). One-year DFS rates with BR-R versus BR-LR were 85% versus 67%, respectively (P ¼ 0.0009). This was due to an imbalance in CR rates post-BR induction and discontinuation due to adverse events (AEs). The most common grade 3-4 AEs for BVR versus BR were neutropenia and sensory neuropathy (12% vs <1%); 83% of the latter occurred with intravenous bortezomib. The most common grade 3-4 AEs related to LR versus rituximab maintenance were neutropenia 66% versus 21%, respectively (P < 0.0001), and febrile neutropenia 10% versus 2%, respectively (P ¼ 0.05). The overall treatment-related mortality was 1.4%. With 5-year median follow-up, 3-year PFS rates for BR-R, BVR-R, and BR-LR were 77%, 82%, and 76%, respectively (P ¼ 0.36) with OS rates of 87%, 90%, and 84%, respectively (P ¼ 0.79). For prognostication, CR rate and POD-24 were associated with survival. Conclusions: Altogether, neither bortezomib added to BR induction nor lenalidomide added to rituximab maintenance immediately post-BR induction is recommended in untreated FL.
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U2 - 10.1158/1078-0432.CCR-20-1345
DO - 10.1158/1078-0432.CCR-20-1345
M3 - Article
C2 - 32532790
AN - SCOPUS:85099623352
SN - 1078-0432
VL - 26
SP - 4468
EP - 4477
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 17
ER -