Characterization of low-grade arthralgia, myalgia, and musculoskeletal pain with ibrutinib therapy: pooled analysis of clinical trials in patients with chronic lymphocytic leukemia and mantle cell lymphoma

Abstract

Joint and muscle pain, including arthralgia, myalgia, and musculoskeletal pain, are among the common adverse events (AEs) reported for ibrutinib, a once-daily Bruton’s tyrosine kinase inhibitor approved for the treatment of various B-cell malignancies, including chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL). This pooled analysis from nine clinical trials of ibrutinib in CLL and MCL (N = 1178) evaluated patterns of these AEs. Any grade arthralgia, myalgia, and musculoskeletal pain occurred in 18%, 10%, and 6% of patients, respectively. AEs were primarily low-grade (grade 1/2: 97‒99%) and occurred during the first year of treatment; most resolved (67%–80%) at first occurrence. Few (<5%) patients required ibrutinib dose modification; no patients discontinued ibrutinib due to these AEs. Among patients evaluated for concomitant medication use, all those receiving concomitant medications after the first AE occurrence experienced AE resolution. These data suggest that these AEs were not treatment-limiting during ibrutinib therapy.

Keywords:

• Ibrutinib
• chronic lymphocytic leukemia
• mantle cell lymphoma
• arthralgia
• myalgia
• musculoskeletal pain

Acknowledgments

We thank all the patients who participated in this trial and their families; David Arthur, PhD, formerly of AbbVie, Inc., for his contributions to data interpretation; and Cindi A. Hoover, PhD, of ApotheCom (San Francisco, CA, USA) for medical writing support, which was funded by Pharmacyclics LLC, an AbbVie Company.

Author contributions

IA-H and AM designed the analysis; TS, SC, DM, PMB, KR, MW, and SO contributed to data collection; AM performed the data analyses; AM and KO-B confirmed the accuracy of the data and compiled it for analysis; and all authors had access to the data and were involved in the interpretation of data, contributed to the manuscript review and revisions, and approved the final version for submission.

Disclosure statement

TS: consulting or advisory role with Juno Therapeutics, Celgene, Kite Pharma, AstraZeneca, and BeiGene; institutional research funding from Kite Pharma, Juno Therapeutics, Celgene, AstraZeneca, TG Therapeutics, Oncternal, BeiGene, and Pharmacyclics LLC, an AbbVie Company; speakers bureau with AstraZeneca, Janssen, and Pharmacyclics LLC, an AbbVie Company; SC: honoraria from Janssen and Pharmacyclics LLC, an AbbVie Company; consulting or advisory role with AbbVie, Celgene, Pharmacyclics LLC, an AbbVie Company, Janssen, Novartis, Astellas, and AstraZeneca; research funding from AbbVie, Acerta, Celgene, Gilead, Janssen, Pharmacyclics LLC, an AbbVie Company, and Takeda; expert testimony for Genentech; travel accommodations from AbbVie, BeiGene, Celgene, Genentech, Janssen, and Pharmacyclics LLC, an AbbVie Company; other relationship with BeiGene; MM: honoraria from Kite Pharma and Genentech; consulting/advisory role with Kite Pharma/Gilead, Seagen, Molecular Templates, BTG, Pharmacyclics, an AbbVie Company, Verastem, Genentech, and Celgene; research funding from Unum Therapeutics, Molecular Templates, Incyte, BeiGene, Denovo Biopharma, Pharmacyclics, an AbbVie Company, Nordic Nanovector, Bristol Myers Squibb, Genentech, and Celgene; speakers bureau with Kite Pharma; PMB: consulting/advisory role with Celgene, Pharmacyclics, an AbbVie Company, AbbVie, Gilead, Seagen, Merck, Genentech, Bristol Myers Squibb, MEI Pharma, Janssen, MorphoSys, AstraZeneca, and TG Therapeutics; research funding from TG Therapeutics and AstraZeneca; KR: consulting/advisory role with Acerta Pharma, AstraZeneca, Innate Pharma, and Pharmacyclics LLC, an AbbVie Company; research funding from Genentech, AbbVie, Novartis, and Janssen; travel accommodations from AstraZeneca; AM: employment with and stock ownership in AbbVie; RV: employment and leadership with Pharmacyclics LLC, an AbbVie Company; stock ownership in AbbVie and Gilead; AS: employment with Pharmacyclics LLC, an AbbVie Company; stock ownership in AbbVie; SD and AZ: employment with and stock ownership in Janssen; IA-H: employment with Janssen; stock ownership in AbbVie and Bristol Myers Squibb; KO-B: employment with, stock ownership in, and travel/accommodations/expenses from AbbVie; MW: honoraria from Acerta Pharma, China Anti-Cancer Association, BeiGene, Breast and Gynecological International Cancer Society, BioInvent, Chinese American Hematologist and Oncologist Network, Chinese Medical Association, Clinical Care Options, Eastern Virginia Medical School, Epizyme, Hebei Cancer Prevention Federation, Imedex, Kite Pharma, TS Oncology, Miltenyi Biomedicine GmBH, Moffitt Cancer Center, Mumbai Hematology Group, Newbridge Pharmaceuticals, Physicians' Education Resource, Practice Point Communications, Scripps Clinic, The First Affiliated Hospital of Zhejiang University, Pharmacyclics LLC, an AbbVie Company, Janssen, AstraZeneca, OMI, Dava Oncology, and OncLive; consulting/advisory role with Pharmacyclics LLC, an AbbVie Company, Bayer Healthcare, BeiGene, BioInvent, CStone Pharmaceuticals, DTRM Biopharma, Epizyme, Genentech, Miltenyi Biomedicine GmBH, VelosBio, Janssen, AstraZeneca, Kite Pharma, Juno, InnoCare, Oncternal, and Loxo Oncology; research funding from BeiGene, Genentech, InnoCare, Eli Lilly, Pharmacyclics LLC, an AbbVie Company, Janssen, AstraZeneca, Kite Pharma, Juno, Celgene, Loxo Oncology, VelosBio, Acerta Pharma, Molecular Templates, BioInvent, and Oncternal; travel accommodations from Physicians' Education Resource, Janssen, Pharmacyclics LLC, an AbbVie Company, AstraZeneca, Acerta Pharma, Juno, Celgene, Kite Pharma, Loxo Oncology, VelosBio, Verastem, Molecular Templates, BioInvent, and Oncternal; SO: consulting/advisory role with Amgen, Astellas, Celgene, GlaxoSmithKline, Janssen, Aptose Biosciences, Vaniam Group, AbbVie, Alexion, Verastem, Eisai, Gilead, Pharmacyclics LLC, an AbbVie Company, TG Therapeutics, Pfizer, Juno Therapeutics, and Sunesis; research funding from Kite Pharma, Regeneron, Acerta, Gilead, Pharmacyclics LLC, an AbbVie Company, TG Therapeutics, Pfizer, and Sunesis.

Data availability statement

Requests for access to individual participant data from clinical studies conducted by Pharmacyclics LLC, an AbbVie Company, can be submitted through Yale Open Data Access (YODA) Project site at http://yoda.yale.edu

Additional information

Funding

This study was funded by Pharmacyclics LLC, an AbbVie Company. Pharmacyclics LLC, an AbbVie Company, sponsored and designed the study. Study investigators and their research teams collected the data. The sponsor confirmed data accuracy and performed analysis of the data. Medical writing support was funded by the sponsor.