Ibrutinib Plus Rituximab (IR) Followed By Short Course R-Hypercvad/MTX in Patients (age ≤ 65 years) with Previously Untreated Mantle Cell Lymphoma - Phase-II Window-1 Clinical Trial

• Published in: Blood 2020-11, Vol.136 (Supplement 1), p.35-36
• Main Authors: Wang, Michael, Jain, Preetesh, Yao, Yixin, Liu, Yang, Zhao, Shuangtao, Hill, Holly, Moghrabi, Omar, Lee, Hun Ju, Samaniego, Felipe, Westin, Jason, Nastoupil, Loretta J., Kanagal-Shamanna, Rashmi, Ok, Chi Young, Chen, Wendy, Oriabure, Onyeka, Che, Yuxuan, Li, Yijing, Feng, Lei, Nogueras González, Graciela M., Xu, Guofang, Wagner-Bartak, Nicolaus, Thirumurthi, Selvi, Santos, David, Tang, Guilin, Vega, Francisco, Yin, C. Cameron, Avellaneda, Michelle, Badillo, Maria, Flowers, Christopher, Wang, Linghua
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2020-137259

Background - We investigated the efficacy and safety of using a combination of ibrutinib plus rituximab (IR) followed by short course (4 cycles) of R-HCVAD/MTX-ara-C as consolidation in previously untreated young (age ≤ 65 years) patients (pts) with mantle cell lymphoma (MCL). Using a chemo-free induction may reduce the toxicities, complications and the risk of second cancers which were observed with intensive chemoimmunotherapy regimen in MCL pts. Methods - We enrolled 131 previously untreated pts in this single institution, single arm, phase II clinical trial - NCT02427620. Pts received IR induction (part-A), until they achieved complete remission (CR) for up to a maximum of 12 cycles, followed by a maximum of 4 cycles of R-HCVAD/R-MTX-ara-C (part-B) as consolidation. None of the pts received stem cell transplant or maintenance therapy. The primary objective was to assess overall response rate (ORR), [defined as either a partial response (PR) or a complete response (CR)] after part A. Adverse events were coded as per CTCAE version 4. Among evaluable samples, minimal residual disease (MRD) by flow cytometry at best response, clonal evolution and MRD using circulating tumor DNA (ctDNA), whole exome (WES) and bulk RNA sequencing from baseline tissue samples was performed. Results - Among the 131 pts, the median age was 56 yrs (range - 35-65). High Ki-67 (≥30%) in 58/117 (49.5%) pts, 10 pts (8%) had high risk simplified MIPI score, 15 pts (11%) had aggressive MCL (blastoid/pleomorphic) and 114 pts (87%) had initial bone marrow involvement. Seventeen pts (13%) had had complex karyotype and 83% had positive SOX-11 expression. Baseline PET scan was available in 101 pts and 97 pts had PET positive disease. Median number of cycles on IR in part A was 7 (1-12). At week 16 on part A, the ORR was 95% (15% CR and 80% PR) and 5% pts had stable disease. Overall best response (ORR) on part A of therapy was 100% (88% CR and 12% PR) and at the time of last follow up after completion of part A and part B, ORR was 100% (98% CR). Median time to CR was 5 months (range 1-16). Pts with CR within 6 months are “early” CR (n=66) and those with CR ≥ 6 months were “late” CR (n=49) while pts who never had CR were grouped as no CR (n=13). With a median follow up of 37 months, the median PFS and OS were not reached (3 year 82% and 95% respectively). Twenty two pts (17%) relapsed after treatment, including 6 who transformed to aggressive MCL. PFS among pts with high and low Ki-67% was 5