Phase I trial of rituximab, lenalidomide, and ibrutinib in previously untreated follicular lymphoma: Alliance A051103 Journal Article

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Authors: Ujjani, C. S.; Jung, S. H.; Pitcher, B.; Martin, P; Park, S. I.; Blum, K. A.; Smith, S. M.; Czuczman, M.; Davids, M. S.; Levine, E.; Lewis, L. D.; Smith, S. E.; Bartlett, N. L.; Leonard, J. P.; Cheson, B. D.
Article Title: Phase I trial of rituximab, lenalidomide, and ibrutinib in previously untreated follicular lymphoma: Alliance A051103
Abstract: Chemoimmunotherapy in follicular lymphoma is associated with significant toxicity. Targeted therapies are being investigated as potentially more efficacious and tolerable alternatives for this multiply-relapsing disease. Based on promising activity with rituximab and lenalidomide in previously untreated follicular lymphoma (ORR 90-96%) and ibrutinib in relapsed disease (ORR 30-55%), the Alliance for Clinical Trials in Oncology conducted a phase I trial of rituximab, lenalidomide, and ibrutinib. Previously untreated patients with follicular lymphoma received rituximab 375 mg/m2 on Day 1, 8, 15, 22 of Cycle 1 and Day 1 of Cycle 4, 6, 8, 10, lenalidomide as per cohort dose on Days 1-21/28 for 18 cycles, and ibrutinib as per cohort dose daily until progression. Dose escalation used a 3+3 design from a starting dose level (DL) of lenalidomide 15 mg and ibrutinib 420 mg (DL0) to DL2 (lenalidomide 20 mg, ibrutinib 560 mg). Twenty-two patients were enrolled; DL2 was determined to be the recommended phase II dose. While no protocol-defined dose-limiting toxicities were reported, a high incidence of rash was observed (all grades 82%, grade 3 36%). Eleven patients (50%) required dose reduction, 7 due to rash. The ORR for the entire cohort was 95%, and the 12-month progression-free survival was 80% (95% CI: 57-92%). Five patients developed new malignancies; 3 had known risk factors prior to enrollment. Given the increased toxicity and required dose modifications, as well as the apparent lack of additional clinical benefit to the rituximab-lenalidomide doublet, further investigation of the regimen in this setting seems unwarranted. The study was registered with www.ClinicalTrials.gov (NCT01829568).
Journal Title: Blood
ISSN: 1528-0020; 0006-4971
Publisher: American Society of Hematology  
Journal Place: United States
Date Published: 2016
Language: ENG
DOI/URL:

blood-2016-06-718106
Notes: LR: 20161005; CI: Copyright (c) 2016; JID: 7603509; 2016/06/02 [received]; 2016/09/23 [accepted]; aheadofprint