Ibrutinib With Rituximab in First-Line Treatment of Older Patients With Mantle Cell Lymphoma
Preetesh Jain, Shuangtao Zhao, Hun Ju Lee, Holly A Hill, Chi Young Ok, Rashmi Kanagal-Shamanna, Fredrick B Hagemeister, Nathan Fowler, Luis Fayad, Yixin Yao, Yang Liu, Omar B Moghrabi, Lucy Navsaria, Lei Feng, Graciela M Nogueras Gonzalez, Guofan Xu, Selvi Thirumurthi, David Santos, Cezar Iliescu, Guilin Tang, L Jeffrey Medeiros, Francisco Vega, Michelle Avellaneda, Maria Badillo, Christopher R Flowers, Linghua Wang, Michael L Wang, Preetesh Jain, Shuangtao Zhao, Hun Ju Lee, Holly A Hill, Chi Young Ok, Rashmi Kanagal-Shamanna, Fredrick B Hagemeister, Nathan Fowler, Luis Fayad, Yixin Yao, Yang Liu, Omar B Moghrabi, Lucy Navsaria, Lei Feng, Graciela M Nogueras Gonzalez, Guofan Xu, Selvi Thirumurthi, David Santos, Cezar Iliescu, Guilin Tang, L Jeffrey Medeiros, Francisco Vega, Michelle Avellaneda, Maria Badillo, Christopher R Flowers, Linghua Wang, Michael L Wang
Abstract
Purpose: Most patients with mantle cell lymphoma (MCL) are older. In this study, we investigated the efficacy and safety of a chemotherapy-free combination with ibrutinib and rituximab (IR) in previously untreated older patients with MCL (age ≥ 65 years).
Methods: We enrolled 50 patients with MCL in this single-institution, single-arm, phase II clinical trial (NCT01880567). Patients with Ki-67% ≥ 50% and blastoid morphology were excluded. Ibrutinib was administered with rituximab up to 2 years with continuation of ibrutinib alone. The primary objective was to assess the overall response rate and safety of IR. In evaluable samples, whole-exome sequencing and bulk RNA sequencing from baseline tissue samples were performed.
Results: The median age was 71 years (interquartile range 69-76 years). Sixteen percent of patients had high-risk simplified MCL international prognostic index. The Ki-67% was low (< 30%) in 38 (76%) and moderately high (≥ 30%-50%) in 12 (24%) patients. The best overall response rate was 96% (71% complete response). After a median follow-up of 45 months (interquartile range 24-56 months), 28 (56%) patients came off study for various reasons (including four progression, 21 toxicities, and three miscellaneous reasons). The median progression-free survival and overall survival were not reached, and 3-year survival was 87% and 94%, respectively. None of the patients died on study therapy. Notably, 11 (22%) patients had grade 3 atrial fibrillation. Grade 3-4 myelosuppression was seen in < 5% of patients. Differential overexpression of CCND1, BIRC3, BANK1, SETBP1, AXIN2, and IL2RA was noted in partial responders compared with patients with complete response.
Conclusion: IR combination is effective in older patients with MCL. Baseline evaluation for cardiovascular risks is highly recommended. Randomized trial is needed for definitive conclusions.
Trial registration: ClinicalTrials.gov NCT01880567 NCT02427620.
Conflict of interest statement
Preetesh JainHonoraria: Kite, a Gilead company, LillyConsulting or Advisory Role: Lilly Hun Ju LeeHonoraria: Aptitude Health, Cancer Experts Now, Curio Science, Century TherapeuticsConsulting or Advisory Role: BMS, Guidepoint Global,Research Funding: Seattle Genetics, BMS, Takeda, Oncternal Therapeutics, Celgene, Chi Young OkResearch Funding: Seattle Genetics Fredrick B. HagemeisterConsulting or Advisory Role: Genentech Nathan FowlerEmployment: BostonGeneConsulting or Advisory Role: Roche/Genentech, TG Therapeutics, Verastem, Bayer, Celgene, Novartis,Research Funding: Roche, Celgene, Gilead Sciences, TG Therapeutics, Novartis, Abbvie, BeiGene Luis FayadConsulting or Advisory Role: EUSA Pharma Francisco VegaHonoraria: i3HealthResearch Funding: CRISPR Therapeutics, Geron Christopher R. FlowersThis author is a member of the Journal of Clinical Oncology Editorial Board. Journal policy recused the author from having any role in the peer review of this manuscript.Consulting or Advisory Role: Bayer, Gilead Sciences¸ Spectrum Pharmaceuticals, Abbvie, Celgene, Denovo Biopharma, BeiGene, Karyopharm Therapeutics, Pharmacyclics/Janssen, Genentech/Roche, EpizymeResearch Funding: Acerta Pharma (Inst), Janssen Oncology (Inst), Gilead Sciences (Inst), Celgene (Inst), TG Therapeutics (Inst), Genentech/Roche (Inst), Pharmacyclics (Inst), Abbvie (Inst), Millennium (Inst), Alimera Sciences (Inst), Xencor (Inst) Michael L. WangHonoraria: Janssen Research & Development, DAVA Oncology, OM Pharmaceutical Industries, AstraZeneca, CAHON, Hebei Cancer Prevention Federation, Mumbai Hematology Group, Acerta Pharma, Anticancer Association, BeiGene, Chinese Medical Association, Clinical Care Options, Epizyme, Imbruvica, Imedex, Kite, a Gilead company, Miltenyi Biomedicine GmbH, Moffit Cancer Center, Newbridge Pharmaceuticals, Physicians Education Resources (PER), Scripps, The First Afflicted Hospital of Zhejiang University, BGICS,Consulting or Advisory Role: AstraZeneca, Janssen Research & Development, Juno Therapeutics, Bioinvent, Pharmacyclics/Janssen, Pulse Biosciences, Guidepoint Global, Loxo, Kite, a Gilead company, InnoCare, Oncternal Therapeutics, CStone Pharmaceuticals, Genentech, Bayer, BeiGene, DTRM Biopharma (Cayman) Limited, Epizyme, Miltenyi Biomedicine GmbH, VelosBioResearch Funding: AstraZeneca, Janssen Research & Development, Pharmacyclics, Kite, a Gilead company¸ Juno Therapeutics, BeiGene, Acerta Pharma, Oncternal Therapeutics, Bioinvent, Loxo, Celgene, VelosBio, Molecular Templates, Lilly, InnoCareTravel, Accommodations, Expenses: Janssen Research & Development, AstraZeneca, Celgene, DAVA Oncology, OM Pharmaceutical IndustriesNo other potential conflicts of interest were reported.
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Source: PubMed