A phase 1/2 clinical trial published in eClinicalMedicine has revealed promising results for the combination of lenalidomide (Revlimid) and obinutuzumab (Gazvya) in patients with relapsed indolent non-Hodgkin lymphoma (NHL). The study, conducted at MD Anderson Cancer Center, aimed to determine the optimal dose and evaluate the safety and efficacy of the combination therapy.
The open-label trial enrolled 66 patients with relapsed or refractory follicular lymphoma (FL), marginal zone lymphoma (MZL), and small lymphocytic lymphoma (SLL), with approximately 85% having FL. Patients received lenalidomide at varying doses combined with a fixed dose of 1000 mg of intravenous obinutuzumab. The recommended phase 2 dose was established as 20 mg of lenalidomide with 1000 mg of obinutuzumab, administered in 28-day cycles for up to 12 cycles.
High Response Rates Observed
The trial met its primary efficacy endpoint, with 90% of patients (n = 54; 95% CI, 79-96) achieving an overall response after six cycles of induction therapy. A complete response was observed in 33% of patients (n = 20; 95% CI, 22-47). After a median follow-up of 41.7 months, the median progression-free survival (PFS), time to progression (TTP), and overall survival (OS) were not reached. The estimated 4-year PFS rate was 55% (95% CI, 42-73), with a TTP of 56% (95% CI, 43-74) and OS of 84% (95% CI, 74-95).
Safety Profile
The safety profile of the combination was consistent with known toxicities of lenalidomide and rituximab, as observed in the AUGMENT trial. The most common Grade 3 or 4 hematological toxicities were neutropenia (21%) and thrombocytopenia (11%). Fatigue (83%), rash (58%), and cough (53%) were the most common non-hematological adverse events, primarily Grade 1 or 2. Grade 3 or 4 non-hematological toxicities included lung infections and fatigue, each affecting 8% of patients. Severe adverse events occurred in 27% of patients, including lung infections (8%), sepsis (5%), and sinus bradycardia (3%).
Outcomes in High-Risk Subgroups
The study also evaluated high-risk subgroups, including patients with disease progression within 24 months of diagnosis (POD24) or those refractory to their last line of therapy. The overall response rate in patients with POD24 was 93% (95% CI, 76-99), with 33% achieving complete responses. The median PFS in this group was 44.2 months (95% CI, 22.5–NA).
Study Limitations and Conclusions
The authors noted that the study's primary limitation is the absence of a control arm, making direct comparisons to standard treatments like rituximab and lenalidomide challenging. However, they concluded that "oral lenalidomide with obinutuzumab is safe and highly active in patients with relapsed and refractory indolent B cell non-Hodgkin lymphoma and is associated with prolonged remission duration."
