A combination of ibrutinib, lenalidomide, and rituximab produced an overall response rate of 76% at 17.8 months median follow-up among 50 adults with relapsed or refractory mantle cell lymphoma, according to an open-label, single-arm, phase 2 trial.

There were complete responses in 28 patients (56%) and partial responses in 10 (20%). Median progression-free survival was 16 months and median overall survival was 22 months. Similar proportions of patients, with and without TP53 mutations, had overall and complete responses, suggesting that triple therapy might be particularly useful in patients with high-risk genetic features.

“Our results provide preliminary evidence that the triplet combination of ibrutinib, lenalidomide, and rituximab is an active regimen in patients with relapsed or refractory mantle cell lymphoma, and should be evaluated in a prospective randomized controlled trial,” wrote Mats Jerkeman, MD, of Lund University, Sweden, and colleagues. The report was published in The Lancet Haematology .

“Addition of lenalidomide to ibrutinib and rituximab might increase the proportion of patients who have complete remission … Previous studies reported complete responses in 44% of patients on ibrutinib and rituximab, in 36% of patients on rituximab and lenalidomide, and in 19% of patients on ibrutinib alone,” they wrote.

However, the complete response benefit might not translate into longer progression-free survival, and the overall response rate was similar to previous studies of ibrutinib alone and in combination with rituximab. There was also greater hematological and cutaneous toxicity with triple therapy, and more infections, including two sepsis deaths.

Treatment was divided into an induction phase of 12 cycles of 28 days with all three drugs and a maintenance phase with ibrutinib and rituximab only, given until disease progression or unacceptable toxicity. All the patients had previously been treated with at least one rituximab-containing regimen.

Janssen and Celgene funded the work. Dr. Jerkeman reported ties to Janssen and Celgene, as well as AbbVie and Gilead.

SOURCE: Jerkeman M et al. Lancet Haematol. 2018 Jan 29. doi: 10.1016/S2352-3026(18)30018-8 .