Dataset Information

A Three-Arm Randomized Phase II Study of Bendamustine/Rituximab with Bortezomib Induction or Lenalidomide Continuation in Untreated Follicular Lymphoma: ECOG-ACRIN E2408.

ABSTRACT:

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 = 0.04). One-year DFS rates with BR-R versus BR-LR were 85% versus 67%, respectively (P = 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 = 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 = 0.36) with OS rates of 87%, 90%, and 84%, respectively (P = 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.

SUBMITTER: Evens AM

PROVIDER: S-EPMC7722783 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A Three-Arm Randomized Phase II Study of Bendamustine/Rituximab with Bortezomib Induction or Lenalidomide Continuation in Untreated Follicular Lymphoma: ECOG-ACRIN E2408.

Evens Andrew M AM Hong Fangxin F Habermann Thomas M TM Advani Ranjana H RH Gascoyne Randy D RD Witzig Thomas E TE Quon Andrew A Ranheim Erik A EA Ansell Stephen M SM Cheema Puneet Singh PS Dy Philip A PA O'Brien Timothy E TE Winter Jane N JN Cescon Terrence P TP Chang Julie E JE Kahl Brad S BS

Clinical cancer research : an official journal of the American Association for Cancer Research 20200612 17

<h4>Purpose</h4>We sought to improve upon frontline bendamustine/rituximab (BR) induction therapy followed by rituximab maintenance in untreated high-risk follicular lymphoma (FL).<h4>Patients and methods</h4>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 di ...[more]

PMID: 32532790

Similar Datasets

Project description:Background:This multicenter, phase II trial tested the tolerability and efficacy of lenalidomide plus rituximab in patients with previously untreated follicular lymphoma (FL). Patients and methods:Patients with grade 1-3a FL, stage 3-4 or bulky stage 2, FL international prognostic index (FLIPI) 0-2, and no prior therapy were eligible to receive rituximab 375?mg/m2 weekly during cycle 1 and day 1 of cycles 4, 6, 8, and 10, plus lenalidomide 20-25?mg on days 1-21 for twelve 28-day cycles. The primary objectives were to evaluate response rates [complete (CR) and overall] and time to progression. Secondary objectives included toxicity, response according to polymorphisms in FcgR2A and FcgR3A, and changes in circulating pro-angiogenic cells. Results:From October 2010 to September 2011, 66 patients were enrolled. Median age was 53?years, 34 were female, 15 had bulky disease, 21 were FLIPI 0-1, 43 FLIPI 2, and 2 FLIPI 3. One patient withdrew before receiving treatment. Fifty-one patients completed 12 cycles of lenalidomide. Reasons for discontinuation included withdrawal (n?=?6), adverse events (n?=?6), progression (n?=?2). Grade 3-4 hematologic toxicity included neutropenia (21%), lymphopenia (9%), and thrombocytopenia (2%), infection (11%), and rash (8%). Grade 1-2 toxicity included fatigue (78%), diarrhea (37%), rash (32%), and febrile neutropenia in one patient. The overall response rate was 95%; the CR rate was 72% (95% confidence interval, 60% to 83%). With a median follow-up of 5?years, the 2- and 5-year progression-free survival were 86% and 70%, respectively, and the 5-year overall survival was 100%. There was no association between CR rate or PFS and FLIPI, histological grade, bulky disease, FcgR2A/FcgR3A polymorphism, or change in circulating endothelial cell/hematopoietic progenitor cell. Conclusion:Lenalidomide plus rituximab was associated with low rates of grade 3-4 toxicity, yielded a CR rate and PFS similar to chemotherapy-based treatment and may represent a reasonable alternative to immunochemotherapy in previously untreated FL. ClinicalTrials.gov Identifier:NCT01145495.

Project description:BackgroundDespite an abundance of therapeutic options, advanced-stage follicular lymphoma remains incurable. Furthermore, the ideal sequence and absolute benefit of post-induction therapy is unclear. We designed SWOG S0801 to assess the efficacy and safety of consolidative radioimmunotherapy and sequential maintenance rituximab following chemoimmunotherapy.MethodsFor this single-arm, phase 2, multicentre study, we enrolled patients aged 18 years and older with a diagnosis of stage III, IV, or bulky stage II follicular lymphoma, grades 1, 2, or 3a, who had not received previous therapy, from from 20 institutions within the United States National Cancer Institute Clinical Trials Network. Patients were assigned to a 5-year treatment plan consisting of R-CHOP (rituximab plus cyclophosphamide [750 mg/m2], doxorubicin [50 mg/m2], vincristine [1·4 mg/m2], and prednisone or prednisolone [100 mg]) every 21 days for up to six cycles, with rituximab 375 mg/m2 given on day 1 of cycles 1-4, followed by 131iodine tositumomab radioimmunotherapy and subsequent maintenance rituximab 375 mg/m2 within 12 weeks after the sixth cycle of R-CHOP, every 3 months for up to 4 years. The primary endpoint was 3-year progression-free survival in the intention-to-treat population. Efficacy and safety analyses were done in the intention-to-treat population and the per-protocol population. This trial was registered with ClinicalTrials.gov, number NCT00770224.FindingsBetween April 1, 2009, and Dec 15, 2010, we enrolled 84 evaluable patients, of whom 73 completed R-CHOP and radioimmunotherapy. Of 69 patients who registered to maintenance therapy, only 41 completed the 4-year rituximab maintenance treatment. Progression-free survival at 3 years was 90% (95% CI 82-95). The most common grade 3 or worse adverse events included neutropenia in 48 (57%) patients, leucopenia in 34 (40%) patients, thrombocytopenia in 17 (20%) patients, and febrile neutropenia in 14 (17%) patients. Nine patients had possible treatment-related deaths during the study from secondary or unknown causes (n=3), cirrhosis (n=1), cardiac arrest (n=1), and secondary malignancies (n=4). Secondary malignancies occurred in seven patients, including two sarcomas, two colorectal carcinomas, two acute myelogenous leukaemias, and one case of renal-cell carcinoma.InterpretationSWOG S0801 showed near universal responses following chemoimmunotherapy and radioimmunotherapy. However, most discontinuations occurred during maintenance therapy, suggesting that rituximab over a 4-year span is not feasible for many patients. Nonetheless, this sequential therapeutic strategy resulted in good overall outcomes for patients, including a low incidence of early disease progression.FundingThe National Cancer Institute and GlaxoSmithKline.

Project description:PurposeLenalidomide and rituximab (LR) are active agents in follicular lymphoma (FL). Combination regimens have not been previously assessed in randomized studies.Patients and methodsThe Cancer and Leukemia Group B (Alliance) 50401 trial is a randomized phase II trial studying rituximab (375 mg/m(2) weekly for 4 weeks), lenalidomide (15 mg per day on days 1 to 21, followed by 7 days of rest, in cycle 1 and then 20 mg per day on days 1 to 21, followed by 7 days of rest, in cycles 2 to 12), or LR. The rituximab-alone arm was discontinued as a result of poor accrual. Eligibility included recurrent FL and prior rituximab with time to progression of ≥ 6 months from last dose. Aspirin or heparin was recommended for patients at high thrombosis risk.ResultsNinety-one patients (lenalidomide, n = 45; LR, n = 46) received treatment; median age was 63 years (range, 34 to 89 years), and 58% were intermediate or high risk according to the Follicular Lymphoma International Prognostic Index. In the lenalidomide and LR arms, grade 3 to 4 adverse events occurred in 58% and 53% of patients, with 9% and 11% of patients experiencing grade 4 toxicity, respectively; grade 3 to 4 adverse events included neutropenia (16% v 20%, respectively), fatigue (9% v 13%, respectively), and thrombosis (16% [n = 7] v 4% [n = 2], respectively; P = .157). Thirty-six percent of lenalidomide patients and 63% of LR patients completed 12 cycles. Lenalidomide alone was associated with more treatment failures, with 22% of patients discontinuing treatment as a result of adverse events. Dose-intensity exceeded 80% in both arms. Overall response rate was 53% (20% complete response) and 76% (39% complete response) for lenalidomide alone and LR, respectively (P = .029). At the median follow-up of 2.5 years, median time to progression was 1.1 year for lenalidomide alone and 2 years for LR (P = .0023).ConclusionLR is more active than lenalidomide alone in recurrent FL with similar toxicity, warranting further study in B-cell non-Hodgkin lymphoma as a platform for addition of novel agents.

Dataset Information

A Three-Arm Randomized Phase II Study of Bendamustine/Rituximab with Bortezomib Induction or Lenalidomide Continuation in Untreated Follicular Lymphoma: ECOG-ACRIN E2408.

Purpose

Patients and methods

Results

Conclusions

Publications

A Three-Arm Randomized Phase II Study of Bendamustine/Rituximab with Bortezomib Induction or Lenalidomide Continuation in Untreated Follicular Lymphoma: ECOG-ACRIN E2408.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure