An open-label phase 1b study of obinutuzumab plus lenalidomide in relapsed/refractory follicular B-cell lymphoma

Franck Morschhauser, Gilles Salles, Steven Le Gouill, Herve Tilly, Catherine Thieblemont, Krimo Bouabdallah, Bettina Fabiani, Cédric Ménard, Karin Tarte, Guillaume Cartron and Roch Houot

Key Points

  • Oral lenalidomide plus obinutuzumab is well tolerated and effective in patients with R/R FL.

  • The recommended dose of lenalidomide in combination with obinutuzumab 1000 mg was established as 20 mg.

Publisher's Note: There is a Blood Commentary on this article in this issue.


Obinutuzumab is a type II anti-CD20 monoclonal antibody that enhances antibody-dependent cellular cytotoxicity better than rituximab. Given promising results with lenalidomide and rituximab, this phase 1b study assessed the safety and efficacy of lenalidomide combined with obinutuzumab (GALEN). Patients age ≥18 years with relapsed or refractory (R/R) follicular lymphoma (FL) after rituximab-containing therapy received escalating doses (10 [n = 7], 15 [n = 3], 20 [n = 6], and 25 mg [n = 3]) of daily oral lenalidomide on days 1 to 21 of cycle 1 and on days 2 to 22 of cycles 2 to 6 (28-day cycles). Obinutuzumab 1000 mg IV was administered on days 8, 15, and 22 (cycle 1) and on day 1 (cycles 2-6). Dose was escalated in a 3 + 3 design based on dose-limiting toxicity (DLT) during cycle 1 to establish the maximum tolerated dose (MTD). We observed 164 adverse events (AEs), of which 139 were grade 1/2. The most common AEs were constipation (52.6%), neutropenia (47.4%), and asthenia (36.8%); 64.3% (9 of 14) of the grade 3/4 AEs were neutropenia/neutrophil decrease, but without any febrile neutropenia. Four DLTs occurred in 2 patients, all deemed unrelated to treatment. MTD was not reached. Twelve patients (63.2%) responded: 8 complete, 3 unconfirmed complete, and 1 partial response. Oral lenalidomide plus obinutuzumab is well tolerated and effective in R/R FL. The recommended dose of lenalidomide was established at 20 mg based on the risk of grade 3/4 neutropenia from cycle 2. This trial was registered at as #NCT01582776.

  • Submitted May 23, 2018.
  • Accepted July 19, 2018.
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