Safety and Efficacy of Ibrutinib Maintenance (I-M) Following Frontline Induction in Mantle Cell Lymphoma (MCL) with Sequential Assessment of Changes in NGS-MRD

• Published in: Blood 2021-11, Vol.138 (Supplement 1), p.3530-3530
• Main Authors: Karmali, Reem, Abramson, Jeremy S., Stephens, Deborah M., Barnes, Jeffrey A, Kaplan, Jason, Winter, Jane N., Ma, Shuo, Gao, Juehua, Petrich, Adam M, Hochberg, Ephraim, Takvorian, Tak, Kuhr, Frank, Lee, Lik Wee, Nelson, Valerie, Gordon, Leo I., Pro, Barbara
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2021-144707

BACKGROUND: Maintenance rituximab in MCL has improved survival and supports the exploration of maintenance with novel targeted agents. Ibrutinib is a BTK inhibitor approved for relapsed/refractory MCL. We report the final analysis of safety and efficacy of Ibrutinib maintenance (I-M) as monotherapy following chemo-immunotherapy induction for treatment-naive MCL in a multicenter phase II trial. METHODS: Pts with CR/PR to frontline chemo-immunotherapy (+/- autologous stem cell transplant (autoSCT)) received I-M 560 mg daily for up to 4 years. The primary endpoint was 3-year PFS rate. Secondary endpoints were to determine PR to CR conversions, median OS and the safety profile of I-M. Minimal residual disease (MRD) was measured using an NGS-MRD assay on peripheral blood (detection resolution of 1 cell per million; clonoSEQ®; Adaptive Biotechnologies) prior to and 1, 6 and 18-24 mo(s) after initiation of I-M. RESULTS: 36 pts were enrolled to complete accrual. Median age was 60 years (range 46-90). For induction, most pts were treated with BR (n=17, 47%) or a cytarabine-containing regimen (n=18, 50%). Eighteen (50%) pts underwent autoSCT. Thirty-four (94%) and 2 (6%) had CR and PR as best response to induction respectively, with 1 PR to CR conversion on I-M. At a median follow-up of 47 months, 10 (28%) pts completed a full I-M course, 7 (19%) remain on I-M, 15 (42%) discontinued I-M for treatment related adverse events (TRAEs) and 4 (11%) discontinued I-M for other reasons (PD x 1, secondary malignancies requiring treatment x 2, death cause unknown x 1). Three pts died during I-M, 2 deaths deemed unrelated to I-M (aspiration pneumonia, 2 nd malignancy) and 1 from unknown cause; 1 pt was lost to follow-up. Four pts were treated with rituximab maintenance after stopping I-M prematurely for toxicity without evidence of disease progression prior to or after change in therapy. At the time of data cut-off, MRD was assessed in 22 of 36 pts (available samples) at varying time points (Fig 1) with a dominant clone identified in all 22 pts. Pts were deemed MRD (-) if no sequences were detected at a threshold of 10 -6. Seventeen pts were MRD (-), 4 MRD indeterminate and 1 MRD (+) with radiographic CR after induction; the latter remained MRD (+) at 18 months with CR. All MRD indeterminate pts were MRD (-) when checked after 1 month on I-M. Six pts MRD (-) post-induction became MRD (+) during their I-M course. Of these pts, 2 reve