Lenalidomide in combination with intravenous rituximab (REVRI) in relapsed/refractory primary CNS lymphoma or primary intraocular lymphoma: a multicenter prospective 'proof of concept' phase II study of the French Oculo-Cerebral lymphoma (LOC) Network and the Lymphoma Study Association (LYSA)
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- 31 March 2019
- journal article
- research article
- Published by Elsevier BV in Annals of Oncology
- Vol. 30 (4), 621-628
- https://doi.org/10.1093/annonc/mdz032
Abstract
Background: Primary central nervous system lymphomas (PCNSLs) are mainly diffuse large B-cell lymphomas (DLBCLs) of the non-germinal center B-cell (non-GCB) subtype. This study aimed to determine the efficacy of rituximab plus lenalidomide (R-2) in DLBCL-PCNSL. Patients and methods: Patients with refractory/relapsed (R/R) DLBCL-PCNSL or primary vitreoretinal lymphoma (PVRL) were included in this prospective phase II study. The induction treatment consisted of eight 28-day cycles of R-2 (rituximab 375/m(2) i.v. D1; lenalidomide 20 mg/day, D1-21 for cycle 1; and 25 mg/day, D1-21 for the subsequent cycles); in responding patients, the induction treatment was followed by a maintenance phase comprising 12 28-day cycles of lenalidomide alone (10 mg/day, D1-21). The primary end point was the overall response rate (ORR) at the end of induction (P0 = 10%; P1 = 30%). Results: Fifty patients were included. Forty-five patients (PCNSL, N = 34; PVRL, N = 11) were assessable for response. The ORR at the end of induction was 35.6% (95% CI 21.9-51.2) in assessable patients and 32.0% (95% CI 21.9-51.2) in the intent-to-treat analysis, including 13 complete responses (CR)/unconfirmed CR (uCR; 29%) and 3 partial responses (PR; 7%). The best responses were 18 CR/uCR (40%) and 12 PR (27%) during the induction phase. The maintenance phase was started and completed by 18 and 5 patients, respectively. With a median follow-up of 19.2 months (range 1.5-31), the median progression-free survival (PFS) and overall survival (OS) were 7.8 months (95% CI 3.9-11.3) and 17.7 months (95% CI 12.9 to not reached), respectively. No unexpected toxicity was observed. The peripheral baseline CD4/CD8 ratio impacted PFS [median PFS = 9.5 months (95% CI, 8.1-14.8] for CD4/CD8 >= 1.6; median PFS = 2.8 months, [95% CI, 1.1-7.8) for CD4/CD8 < 1.6, P = 0.03). Conclusions: The R-2 regimen showed significant activity in R/R PCNSL and PVRL patients. These results support assessments of the efficacy of R-2 combined with methotrexate-based chemotherapy as a first-line treatment of PCNSL.Funding Information
- Celgene Corporation
- Summit
- NJ
- Roche France
This publication has 16 references indexed in Scilit:
- Phase II Trial of Temsirolimus for Relapsed/Refractory Primary CNS LymphomaJournal of Clinical Oncology, 2016
- Primary CNS lymphoma at first relapse/progression: characteristics, management, and outcome of 256 patients from the French LOC networkNeuro-Oncology, 2016
- Oral lenalidomide with rituximab in relapsed or refractory diffuse large cell, follicular and transformed lymphoma: a phase II clinical trialLeukemia, 2013
- Single‐agent lenalidomide in relapsed/refractory mantle cell lymphoma: results from a UK phase II study suggest activity and possible gender differencesBritish Journal of Haematology, 2012
- Higher response to lenalidomide in relapsed/refractory diffuse large B‐cell lymphoma in nongerminal center B‐cell–like than in germinal center B‐cell–like phenotypeCancer, 2011
- Relapse of primary central nervous system lymphoma: clinical features, outcome and prognostic factorsJournal of Neuro-Oncology, 2006
- A uniform activated B-cell–like immunophenotype might explain the poor prognosis of primary central nervous system lymphomas: analysis of 83 casesBlood, 2005
- Design Issues of Randomized Phase II Trials and a Proposal for Phase II Screening TrialsJournal of Clinical Oncology, 2005
- Immunomodulatory Drug CC-5013 or CC-4047 and Rituximab Enhance Antitumor Activity in a Severe Combined Immunodeficient Mouse Lymphoma ModelClinical Cancer Research, 2005
- Report of an International Workshop to Standardize Baseline Evaluation and Response Criteria for Primary CNS LymphomaJournal of Clinical Oncology, 2005