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1688 Six Years Follow up of Ibrutinib Plus Rituximab (IR) Followed By Short Course R-Hyper CVAD/MTX in Patients (age ≤ 65 years) with Previously Untreated Mantle Cell Lymphoma – Phase-II Window-1 Clinical Trial

Program: Oral and Poster Abstracts
Session: 623. Mantle Cell, Follicular, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Research, clinical trials, Clinical Research
Saturday, December 9, 2023, 5:30 PM-7:30 PM

Preetesh Jain, MD, MBBS, PhD, DM1, Hun Ju Lee, MD2*, Jason Westin, MD3, Loretta J. Nastoupil, MD4, Luis Fayad, MD5, Ranjit Nair, MD6, Swami P. Iyer, MD1, Rashmi Kanagal-Shamanna, MD7, Ahmed Fetooh, MD8*, Holly A Hill, MS9*, Chi Young Ok, MD10, Wendy Chen, BS, MPAS, MS9*, Onyeka Oriabure, MSN, RN, NP9*, Lei Feng, MS11*, Guilin Tang, MD, PhD10*, Francisco Vega, MD, PhD12, Maria Badillo8*, Christopher R. Flowers, MD, MS2 and Michael L. Wang, MD13

1Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX
2Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX
3Department of Lymphoma and Myeloma, The University of Texas M D Anderson Cancer Center, Houston, TX
4MD Anderson Cancer Center, Houston, TX
5Lymphoma/Myeloma, M.D. Anderson Cancer Center, Houston, TX
6Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Pearland, TX
7Hematopathology, MD Anderson Cancer Center, Houston, TX
8Lymphoma/ Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX
9Departments of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX
10Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX
11Biostatistics, UT MD Anderson Cancer Center, Houston, TX
12Department of Hematopathology, MD Anderson Cancer Center , Houston, TX
13Lymphoma/ Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX

Background – We reported the efficacy and safety of using a combination of ibrutinib plus rituximab (IR) induction 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), Wang M et al Lancet Oncology 2022. Here we report the long term follow up of this study.

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. 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. High risk pts received ibrutinib for 1 year and rituximab once every 2 months for 24 months after completion of part B.

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. Fifty percent of the patients had Ki-67 (≥30%). ORR in part-A was 98% (87% CR). After completion of part A and part B, ORR was 90% (89% CR). After a median follow up of 71 months, 43 patients progressed/died. The median progression free survival (PFS) and overall survival (OS) were not reached. Overall, 30 pts (23%) relapsed after treatment, including 5 who transformed to aggressive MCL. PFS among pts with high and low Ki-67% was 42 months vs not reached (P=0.01) while no difference was observed in OS. PFS was significantly shorter in pts with aggressive histology (p=0.001) but not the OS. PFS was similar in pts who received maintenance vs no maintenance therapy. Overall, 8 pts died (4 with progression, 2 due to disease transformation, one on study due to multiple complications including splenic hematoma, cardio-pulmonary arrest and progression and the last one expired outside and came off study due to encephalitis). 50 pts came off study for various reasons [30 disease progression (including 5 transformation), 10 pt choice, 8 intolerance, 1 second cancer and 1 lost to follow up]. Long term, grade 3-4 toxicities on part A were 6% myelosuppression and 10% each with fatigue, myalgia and rashes and 2% mucositis. Maintenance therapy did not show high toxicities.

Conclusions Long term follow up of chemo-free induction with IR induced durable and deep responses in young MCL pts in the frontline setting. Short course R-HCVAD chemotherapy minimized toxicities and consolidated responses. IR maintenance improved survival outcomes. This combined modality treatment approach may significantly improve young MCL pts outcomes across all risk groups.

Disclosures: Jain: AstraZeneca: Consultancy, Honoraria. Lee: Guidepoint: Honoraria; Celgene: Research Funding; Cancer Experts: Honoraria; Deloitte: Honoraria; Bristol-Myers Squibb: Research Funding; Seagen Inc.: Research Funding; Century Therapeutics: Consultancy; Aptitude Health: Honoraria; Oncternal Therapeutics: Research Funding; Curio Sciences: Honoraria; Janssen: Honoraria; Takeda: Research Funding; Pharmacyclics: Research Funding; Olson Research: Honoraria; Korean Society of Cardiology: Honoraria. Westin: Genentech: Consultancy, Research Funding; SeaGen: Consultancy; Nurix: Consultancy; ADC Therapeutics: Consultancy, Research Funding; Abbvie: Consultancy; Morphosys/Incyte: Consultancy, Research Funding; MonteRosa: Consultancy; Novartis: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Calithera: Research Funding; Kymera: Research Funding; Kite/Gilead: Consultancy, Research Funding. Nastoupil: ADC Therapeutics: Honoraria; AbbVie: Honoraria; Caribou Biosciences: Honoraria, Research Funding; Bristol Myers Squibb/Celgene: Honoraria, Research Funding; DeNovo: Honoraria; Daiichi Sankyo: Honoraria, Research Funding; Genentech, Inc., Genmab, Gilead/Kite, Janssen, Merck, Novartis, Takeda: Honoraria, Research Funding; Regeneron: Honoraria; AstraZeneca: Honoraria; Gilead Sciences/Kite Pharma: Honoraria, Research Funding. Iyer: Yingli: Consultancy, Research Funding; CRISPR: Consultancy, Research Funding; Innate: Research Funding; Acrotech: Consultancy, Research Funding; Legend: Research Funding; Astra Zeneca: Research Funding; Ono: Research Funding; Pfizer: Research Funding; Salarius: Consultancy; Drenbio: Research Funding; Merck: Research Funding; American Society of Transplant and Cellular Therapy: Speakers Bureau; CuraBio: Speakers Bureau; American Society of Hematology: Speakers Bureau; Seagen: Consultancy, Research Funding. Vega: Geron: Research Funding; Allogene: Research Funding. Flowers: Eastern Cooperative Oncology Group: Research Funding; Genmab: Consultancy; Iovance: Research Funding; Cellectis: Research Funding; Guardant: Research Funding; Burroghs Wellcome Fund: Research Funding; V Foundation: Research Funding; Cancer Prevention and Research Institute of Texas: Research Funding; National Cancer Institute: Research Funding; Allogene: Research Funding; Ziopharm: Research Funding; Xencor: Research Funding; Takeda: Research Funding; Pharmacyclics: Research Funding; Sanofi: Research Funding; Adaptimmune: Research Funding; Amgen: Research Funding; Jannsen Pharmaceuticals: Research Funding; Kite: Research Funding; Morphosys: Research Funding; Nektar: Research Funding; Novartis: Research Funding; Pfizer: Research Funding; Karyopharm: Consultancy; 4D: Research Funding; Acerta: Research Funding; Bayer: Consultancy, Research Funding; Beigene: Consultancy; Celgene: Consultancy, Research Funding; Denovo Biopharma: Consultancy; Foresight Diagnostics: Consultancy, Current holder of stock options in a privately-held company; Genentech Roche: Consultancy, Research Funding; N-Power Medicine: Consultancy, Current holder of stock options in a privately-held company; Spectrum: Consultancy; SeaGen: Consultancy; Pharmacyclics Jansen: Consultancy; Abbvie: Consultancy, Research Funding; TG Therapeutics: Research Funding; Gilead: Consultancy, Research Funding; CPRIT Scholar in Cancer Research: Research Funding. Wang: Miltenyi Biomedicine: Consultancy; Genmab: Honoraria, Research Funding; i3Health: Honoraria; Merck: Consultancy, Honoraria; Meeting Minds Experts: Honoraria; Medscape: Honoraria; MJH Life Sciences: Honoraria; Moffit Cancer Center: Honoraria; MD Education: Honoraria; DTRM Biopharma (Cayman) Limited: Consultancy; NIH: Honoraria; Eli Lilly and Company: Consultancy, Research Funding; Nurix: Honoraria; IDEOlogy Health: Honoraria; Dava Oncology: Honoraria, Other: Travel; Bantam Pharmaceutical: Honoraria; Pepromene Bio: Consultancy; Pharmacyclics: Consultancy, Honoraria, Research Funding; VelosBio: Consultancy, Research Funding; Milken Institute: Consultancy; Oncternal: Consultancy, Research Funding; Parexel: Consultancy; Eastern Virginia Medical School: Honoraria; Leukemia & Lymphoma Society: Consultancy, Honoraria; Kite Pharma: Consultancy, Honoraria, Other: Travel, Research Funding; Genentech: Consultancy; InnoCare: Consultancy; Janssen: Consultancy, Honoraria, Research Funding; CAHON: Honoraria; Juno Therapeutics: Research Funding; Genentech: Research Funding; Celgene: Other: Travel, Research Funding; WebMD: Honoraria; Studio ER Congressi: Honoraria; Scripps: Honoraria; Practice Point Communications (PPC): Honoraria; Physicians Education Resources (PER): Honoraria, Other: Travel; Oncology Specialty Group: Honoraria; OncLive: Honoraria; Deciphera: Consultancy; Bristol Myers Squibb: Consultancy, Honoraria; BioInvent: Consultancy, Honoraria, Research Funding; BeiGene: Consultancy, Honoraria, Research Funding; Be Biopharma: Consultancy; AstraZeneca: Consultancy, Honoraria, Other: Travel, Research Funding; Amphista Therapeutics Limited: Consultancy; ADC Therapeutics America: Consultancy; Acerta Pharma: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria; Loxo Oncology: Research Funding; Molecular Templates: Research Funding; Vincerx: Research Funding.

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