Obinutuzumab plus lenalidomide in advanced, previously untreated follicular lymphoma in need of systemic therapy: a LYSA study.

Abstract

Obinutuzumab and lenalidomide (referred to as the GALEN combination) is an active immunomodulatory combination with a manageable safety profile in multiple types of lymphoma. We report efficacy and safety results for the phase 2 GALEN study in previously untreated patients with advanced follicular lymphoma (FL). Eligible patients aged ≥18 years had an Eastern Cooperative Oncology Group performance status ≤2 and high-tumor burden, grade 1 to 3a FL. Induction treatment was obinutuzumab (1000 mg IV, days 8, 15, and 22, cycle 1; day 1, cycles 2-6) plus lenalidomide (20 mg/d, days 1-21, cycle 1; days 2-22, cycles 2-6) for six 28-day cycles. Maintenance included obinutuzumab (1000 mg every 2 cycles) plus lenalidomide (10 mg, days 2-22) for ≤12 cycles (year 1) followed by obinutuzumab (1000 mg every 56 days) for 6 cycles (year 2). The primary end point was complete response rate (CRR) after induction per the 1999 International Working Group criteria. From October 2015 to February 2017, a total of 100 patients were enrolled. CRR after induction was 47%, and the overall response rate (ORR) was 92%. Post hoc analyses per the 2014 Lugano classification, including patients with missing bone marrow assessments, identified an additional 13 patients fulfilling CRR criteria, resulting in a complete metabolic response of 80% and an ORR of 94%. At a median follow-up of 3.7 years, 3-year progression-free survival and overall survival were 82% and 94%, respectively. The most common adverse event was neutropenia (48% any grade; 47% grade ≥3). Only 2% of patients presented with febrile neutropenia; others were mainly grade ≤2. No other specific grade ≥3 toxicity occurred at a frequency >3%. Overall, these results showed promising clinical efficacy for the chemotherapy-free GALEN backbone in previously untreated patients with high tumor burden FL. Except for neutropenia, the safety profile of the combination is remarkable. The study was registered at clinicaltrials.gov as #NCT01582776.

• Authors: Emmanuel Bachy, Roch Houot, Pierre Feugier, Krimo Bouabdallah, Reda Bouabdallah, Emmanuelle Nicolas Virelizier, Marie Maerevoet, Christophe Fruchart, Sylvia Snauwaert, Steven Le Gouill, Jean-Pierre Marolleau, Lysiane Molina, Cécile Moluçon-Chabrot, Catherine Thieblemont, Hervé Tilly, Fontanet Bijou, Corinne Haioun, Eric Van den Neste, Bettina Fabiani, Michel Meignan, Guillaume Cartron, Gilles Salles, Olivier Casasnovas, Franck Morschhauser
• Journal: Blood (Blood) Vol. 139 Issue 15 Pg. 2338-2346 (04 14 2022) ISSN: 1528-0020 [Electronic] United States
• PMID: 34936697 (Publication Type: Journal Article)
• Copyright: © 2022 by The American Society of Hematology.

Chemical References

• Antibodies, Monoclonal, Humanized
• Lenalidomide
• obinutuzumab

Topics

• Adolescent
• Adult
• Antibodies, Monoclonal, Humanized
• Antineoplastic Combined Chemotherapy Protocols (adverse effects)
• Humans
• Lenalidomide (therapeutic use)
• Lymphoma, Follicular (pathology)
• Neutropenia (drug therapy)
• Treatment Outcome