Ibrutinib Maintenance Following Frontline Treatment in Patients with Mantle Cell Lymphoma.

Maintenance rituximab in MCL has improved survival and supports exploration of maintenance with novel agents. We evaluated the safety and efficacy of Ibrutinib maintenance (I-M) following induction in patients with treatment-naive MCL. Patients with MCL with CR/PR to frontline chemo-immunotherapy +/- autologous stem cell transplantation (autoSCT) received I-M 560 mg daily for up to 4 years. Primary objective was 3-year PFS rate from initiation of I-M. Minimal residual disease (MRD) assessments by NGS on peripheral blood were measured prior to I-M initiation and at 1, 6 and 18-24 mo(s) post initiation. Among 36 patients, median age was 60 (range 46-90). For frontline treatment, 18 (50%) had consolidation with autoSCT in CR1 prior to I-M. At median follow-up of 55.7 months, 17 (47 %) patients completed full course I-M (median 37.5 cycles, range 2-52). The 3-year PFS and OS rates were 94% and 97% respectively. With prior autoSCT, 3-year PFS and OS rates were both 100%. The most common treatment related adverse event (TRAE) with I-M was infection (n=31, 86%), typically low grade; the most common grade 3/4 toxicities were hematologic. In 22 patients with MRD assessments, all were MRD (-) after induction. Six became MRD (+) on I-M with 2 reverting to MRD (-) status with continued I-M and all maintain radiographic CR with the exception of 1 with disease progression. I-M is feasible in MCL after frontline chemo-immunotherapy with manageable toxicities though significant. Changes in NGS-MRD were noted in limited patients during maintenance with few progression and survival events.