AUGMENT: A Phase III Study of Lenalidomide Plus Rituximab Versus Placebo Plus Rituximab in Relapsed or Refractory Indolent Lymphoma

Abstract

PURPOSE Patients with indolent non-Hodgkin lymphoma typically respond well to first-line immunochemotherapy. At relapse, single-agent rituximab is commonly administered. Data suggest the immunomodulatory agent lenalidomide could increase the activity of rituximab. METHODS A phase III, multicenter, randomized trial of lenalidomide plus rituximab versus placebo plus rituximab was conducted in patients with relapsed and/or refractory follicular or marginal zone lymphoma. Patients received lenalidomide or placebo for 12 cycles plus rituximab once per week for 4 weeks in cycle 1 and day 1 of cycles 2 through 5. The primary end point was progression-free survival per independent radiology review. RESULTS A total of 358 patients were randomly assigned to lenalidomide plus rituximab (n = 178) or placebo plus rituximab (n = 180). Infections (63% v 49%), neutropenia (58% v 23%), and cutaneous reactions (32% v 12%) were more common with lenalidomide plus rituximab. Grade 3 or 4 neutropenia (50% v 13%) and leukopenia (7% v 2%) were higher with lenalidomide plus rituximab; no other grade 3 or 4 adverse event differed by 5% or more between groups. Progression-free survival was significantly improved for lenalidomide plus rituximab versus placebo plus rituximab, with a hazard ratio of 0.46 (95% CI, 0.34 to 0.62; P < .001) and median duration of 39.4 months (95% CI, 22.9 months to not reached) versus 14.1 months (95% CI, 11.4 to 16.7 months), respectively. CONCLUSION Lenalidomide improved efficacy of rituximab in patients with recurrent indolent lymphoma, with an acceptable safety profile.

Prolonged follow‐up on lenalidomide‐based treatment for mucosa‐associated lymphoid tissue lymphoma (MALT lymphoma)—Real‐world data from the Medical University of Vienna

“…Toxicity profiles were favorable for both treatment schedules with moderate skin adverse events being the main reported side effect. In addition to our data, there is also evidence from larger phase II and III studies including mixed collectives of indolent lymphoma that LEN is an active and safe drug in this disease, but results are once again inconsistent due to only small subgroups of MZL included, particularly in the relapsed/refractory setting …”

“…Application of LEN has become a widely used approach in various lymphoid malignancies including follicular lymphoma in combination with rituximab, as well as in mantle cell lymphoma . In this article, we present our long‐term experience with patients suffering from MALT lymphoma undergoing a chemo‐free immunomodulatory therapy based on the application of the IMiD LEN either as monotherapy (n = 16) or in combination with rituximab (n = 34).…”

Response‐adapted treatment with rituximab, bendamustine, mitoxantrone, and dexamethasone followed by rituximab maintenance in patients with relapsed or refractory follicular lymphoma after first‐line immunochemotherapy: Results of the RBMDGELTAMO08 phase II trial

“…High response rates have been reported for the immunomodulator lenalidomide and for PI3K inhibitors. The Augment study of 358 patients with relapsed indolent lymphoma (84% FL; median number of previous treatments, 1) reported an ORR of 78%, CR of 34%, and a median PFS of 39.4 months after treatment with lenalidomide plus rituximab, although patients refractory to rituximab or rituximab combinations were excluded . Based on the results of phase II studies, three PI3K inhibitors (idelalisib, copanlisib, and duvelisib) are currently available for the treatment of FL that has relapsed or is refractory after two or more previous lines of therapy .…”

Efficacy of lenalidomide in high‐risk diffuse large B‐cell lymphoma

“…Durable clinical activity was observed in transformed FL, consistent with the known activity in low‐grade FL (Leonard et al ., ). In our study, patients with transformed FL had a median PFS of two years with an OS of nearly four years.…”