Ibrutinib With Rituximab in First-Line Treatment of Older Patients With Mantle Cell Lymphoma

J Clin Oncol. 2022 Jan 10;40(2):202-212. doi: 10.1200/JCO.21.01797. Epub 2021 Nov 19.


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.

Publication types

  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / adverse effects
  • Adenine / analogs & derivatives*
  • Adenine / therapeutic use
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / genetics
  • Disease Progression
  • Exome Sequencing
  • Female
  • Humans
  • Lymphoma, Mantle-Cell / drug therapy*
  • Lymphoma, Mantle-Cell / genetics
  • Lymphoma, Mantle-Cell / mortality
  • Male
  • Piperidines / adverse effects
  • Piperidines / therapeutic use*
  • Progression-Free Survival
  • Rituximab / adverse effects
  • Rituximab / therapeutic use*
  • Sequence Analysis, RNA
  • Time Factors


  • Biomarkers, Tumor
  • Piperidines
  • ibrutinib
  • Rituximab
  • Adenine

Associated data

  • ClinicalTrials.gov/NCT01880567
  • ClinicalTrials.gov/NCT02427620