Phase 1b dose-finding study of rituximab, lenalidomide, and ibrutinib (R2I) in patients with relapsed/refractory mantle cell lymphoma

Abstract

Mantle cell lymphoma (MCL) is a rare non-Hodgkin lymphoma that frequently becomes chemoresistant over time. The distinct mechanisms of ibrutinib and lenalidomide provided a judicious rationale to explore the combination with anti-CD20 immunotherapy. In this phase 1b study (NCT02446236), patients (n = 25) with relapsed/refractory MCL received rituximab with escalating doses of lenalidomide (days 1–21) and ibrutinib 560 mg (days 1–28) of 28-day cycles. The MTD for lenalidomide was 20 mg; most common grade ≥3 adverse events were skin rashes (32%) and neutropenic fever (24%). The best ORR was 88%, CR rate was 83%, and median duration of response (DOR) was 36.92 months (95% CI 33.77, 51.37). Responses were seen even in refractory patients or with high-risk features (e.g. blastoid variant, TP53 mutation, Ki-67 > 30%). R2I was safe and tolerable in patients with R/R MCL.

Keywords:

• Ibrutinib
• lenalidomide
• rituximab
• mantle cell lymphoma
• R2I

Authors’ contributions

Conception and design: AI, AHG; administrative support: JZ, LP; provision of study materials or patients: AI, TF, LAL, AHG; collection and assembly of data: AP, SG, JZ, MG, VB, AN, AD, GL; data analysis and interpretation: AP, SG, ADP, VB, AN, AHG, AI, AD, GL, JZ, JA; manuscript writing: All authors; Final approval of manuscript: All authors.

Data availability statement

The data that support the findings of this study are available on request from the corresponding author, AI. The data are not publicly available due to their containing information that could compromise the privacy of research participants. The study involves a review of the electronic medical records of mantle cell lymphoma patients who received R2I. The research data set has removed most, but not all protected health information (for example: actual dates of response assessments and treatment were included as needed for analysis but would be considered PHI). The dataset is also considered property of Hackensack Meridian Health and not owned by the investigators. Therefore, for both reasons, the dataset cannot be made openly available. However, upon request we are willing to share portions of the data for appropriate review. Requests can be made through the corresponding author or directly to representatives of Hackensack Meridian Health (Dr. Andrew Ip; Email: [email protected]).

Additional information

Funding

This study was funded by Celgene Corporation, a subsidiary of Bristol Myers Squibb, Lawrenceville, NJ, USA.