Combination of Ibrutinib with Rituximab (IR) in Previously Untreated Older Patients with Mantle Cell Lymphoma (MCL) - a Phase II Clinical Trial

• Published in: Blood 2020-11, Vol.136 (Supplement 1), p.41-42
• Main Authors: Jain, Preetesh, Yao, Yixin, Zhao, Shuangtao, Liu, Yang, Hill, Holly, Che, Yuxuan, Li, Yijing, Jordan, Alexa A, McIntosh, Joseph, Lee, Hun Ju, Steiner, Raphael Eric, Samaniego, Felipe, Westin, Jason, Nastoupil, Loretta J., Nair, Ranjit, Ahmed, Sairah, Ok, Chi Young, Kanagal-Shamanna, Rashmi, Oriabure, Onyeka, Xu, Guofang, Chen, Wendy, Moghrabi, Omar, McClain, Chloe Marie, Badillo, Maria, Thirumurthi, Selvi, Santos, David, Iliescu, Cezar, Yin, C. Cameron, Li, Shaoying, Tang, Guilin, Vega, Francisco, Neelapu, Sattva S., Flowers, Christopher, Wang, Linghua, Wang, Michael
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2020-137167

Background - Older patients (pts) with mantle cell lymphoma (MCL) may exhibit poor functional status and become ineligible for intensive chemo-immunotherapy or stem cell transplantation. The advent of chemotherapy-free therapies are a significant advance in MCL. We investigated the safety and efficacy of combining ibrutinib and rituximab (IR) in previously untreated older pts (age ≥65 years) with MCL in a single center, phase II clinical trial. Methods - We enrolled previously untreated pts with MCL ≥65 years (n=50) in this study (NCT01880567). Pts with Ki-67% ≥ 50%, blastoid/pleomorphic histology and those with clinically uncontrolled co-morbidities (including atrial fibrillation) were excluded from this study. Pts received ibrutinib 560 mg orally daily for 28 days (one cycle) continued until disease progression or discontinued for any reason. Rituximab was given on days 1, 8, 15 and 22 +/- 1 day by IV infusion at a fixed dose of 375 mg/m2 in cycle 1, followed by rituximab on day 1 of every cycle for cycles 3 - 8. Following cycle 8, rituximab was given on day 1 every 2 months for up to 2 years. The primary objective was to assess the safety and response of IR. For pts with evaluable samples, minimal residual disease (MRD) by flow cytometry at best response, whole exome (WES) and bulk RNA sequencing from baseline tissue samples was performed. Results - Among 50 pts enrolled, the median age was 71 years (range 65-84), 76% were males, ECOG PS was (0) in 42 (84%) pts, 16% had high risk MCL international prognostic index, 48 (96%) pts had initial bone marrow involvement, and 19 (79%) of 24 evaluable pts had baseline GI involvement by MCL. The Ki-67% was low (