KEY TAKEAWAYS
- The study aimed to investigate the safety and efficacy of IRR therapy in patients with untreated FL and MZL.
- The primary endpoint was to determine PFS.
- Researchers noticed that IRR therapy is highly active in patients with untreated FL and MZL but has higher grade 3-4 toxicity.
Follicular lymphoma (FL) and marginal zone lymphoma (MZL) are indolent non-Hodgkin lymphomas (iNHL). Median survival for iNHL is approximately 20 years. Because standard treatments are not curative, patients often receive multiple lines of therapy with associated toxicity.
Rationally designed combination therapies with curative potential are needed. The immunomodulatory drug lenalidomide was evaluated in combination with rituximab for the frontline treatment of FL in the phase 3 RELEVANCE study. Ibrutinib, an oral Bruton tyrosine kinase inhibitor, is active in NHL and was evaluated in combination with IRR in a phase 1 study.
Max J Gordon and the team aimed to assess the safety and efficacy of the combination therapy of ibrutinib, rituximab, and lenalidomide (IRR) in patients with previously untreated FL & MZL.
They performed an inclusive analysis by conducting an open-label, phase 2 clinical trial of IRR for previously untreated FL and MZL. The primary endpoint was progression-free survival (PFS) at 24 months.
About 48 participants with previously untreated FL grade 1-3a (N = 38) or MZL (N = 10) were included in this study. Participants received 12, 28-day cycles of lenalidomide (15 mg, days 1-21 cycle 1; 20 mg, cycles 2-12), rituximab (375 mg/m2 weekly in cycle 1; day 1 cycles 2-12), and ibrutinib 560 mg daily.
With a median follow-up of 65.3 months, the estimated PFS at 24 months was 78.8% (95% confidence interval [CI], 68.0%-91.4%), and the 60-month PFS was 59.7% (95% CI, 46.6%-76.4%). One death occurred unrelated to disease progression. Grade 3-4 adverse events were observed in 64.6%, including 50% with grade 3-4 rash.
The study concluded that IRR is highly active as frontline therapy for FL and MZL. Compared to historical results with lenalidomide and rituximab, the PFS is similar; however, there is a higher incidence of grade 3-4 toxicity, particularly rash.
The study was sponsored by the M.D. Anderson Cancer Center.
Source: https://pubmed.ncbi.nlm.nih.gov/37985359/
Clinical Trial: https://clinicaltrials.gov/study/NCT02532257
Gordon MJ, Feng L, Strati P, et al. (2024). “Safety and efficacy of ibrutinib in combination with rituximab and lenalidomide in previously untreated follicular and marginal zone lymphoma: An open label, phase 2 study.” Cancer. 2024 Mar 15;130(6):876-885. doi: 10.1002/cncr.35114. Epub 2023 Nov 20. PMID: 37985359; PMCID: PMC10922670.
