The iR

Background

This phase 1b/2 PCYC-1123-CA study evaluated efficacy and safety of the combination of ibrutinib, lenalidomide, and rituximab (iR

Methods

In phase 2, patients with relapsed/refractory non-germinal centre B-cell-like DLBCL received oral ibrutinib 560 mg once daily and oral lenalidomide 20 mg or 25 mg once daily on Days 1-21 of each 28-day cycle until disease progression or unacceptable toxicity and intravenous rituximab 375 mg/m

Findings

Between March 13, 2014 and October 2, 2018, 89 patients were enrolled with a median time on study of 35.0 months. Best ORR in the response-evaluable population (n = 85) was 49% (95% confidence interval [CI], 38-61) across dose cohorts and 53% (95% CI, 39-67) and 44% (95% CI, 26-62) in the 20 mg and 25 mg lenalidomide cohorts, respectively, with complete responses in 24/85 (28%), 17/53 (32%), and 7/32 (22%) patients, respectively. Grade 3/4 adverse events (AEs) occurred in 81/89 patients (91%), most frequently neutropenia (36/89; 40%), maculopapular rash (16/89; 18%), anaemia (12/89; 13%), and diarrhoea (9/89; 10%). Serious adverse events occurred in 57/89 patients (64%). Fatal AEs occurred in 12/89 patients (13%); causes of death were worsening of DLBCL (n = 7), pneumonia (n = 3), sepsis (n = 1), and cardiac arrest (n = 1).

Interpretation

The most frequent AEs (diarrhoea, neutropenia, fatigue, cough, anaemia, peripheral oedema, and maculopapular rash) were consistent with known safety profiles of the individual drugs. The iR

Funding

Pharmacyclics LLC, an AbbVie Company.

Informations de copyright

© 2022 The Authors.

Déclaration de conflit d'intérêts

R.R. reports a consulting/advisory role with Pharmacyclics LLC, an AbbVie Company; and research funding from Janssen and Pharmacyclics LLC, an AbbVie Company. P.J. reports honoraria from Bristol-Myers Squibb, Genmab, Incyte, Kymera, MorphoSys, Novartis, and Takeda; a consulting/advisory role for Epizyme and Janssen; and patents/royalties/other intellectual property with the University of Southampton. N.G. reports a consulting/advisory role for AbbVie, ADC Therapeutics, Adaptive Biotech, BeiGene, Bristol Myers Squibb, Genmab, Gilead/Kite, Incyte, Janssen, TG Therapeutics, and Pharmacyclics LLC, an AbbVie Company; research funding from Bristol Myers Squibb, Genentech, TG Therapeutics, and Pharmacyclics LLC, an AbbVie Company; and speakers bureau for AbbVie, Bristol Myers Squibb, Epizyme, Gilead/Kite, Janssen, and Pharmacyclics LLC, an AbbVie Company. JRu reports a consulting/advisory role for Celgene/Bristol Myers Squibb, Daiichi Sankyo, Kite Pharma, Seagen, and Secura Bio; and research funding from AstraZeneca, Celgene/Bristol Myers Squibb, Daiichi Sankyo, and Genentech. K.M.A. reports honoraria from and a consulting/advisory role for BeiGene, Celgene, Gilead, Novartis, and Roche; research funding from ADC Therapeutics, Autolus, Bristol Myers Squibb, Janssen, Novartis, and Pharmacyclics LLC, an AbbVie Company; and travel/accommodations/expenses from Celgene, Gilead, Novartis, and Roche. R.J. reports honoraria from Gilead and Novartis; and a consulting/advisory role for Gilead, Novartis, and Takeda. G.V., S.d.V., S.K., and F.O. have nothing to disclose. D.C. reports a consulting/advisory role with OVIBIO; and research funding from 4SC, Bayer, Celgene, Clovis, Eli Lilly, Leap, MedImmune/AstraZeneca, the National Institute for Health and Care Research Efficacy and Mechanism Evaluation Programme, and Roche. L.F. reports honoraria from and a consulting/advisory role for EUSA Pharma; and research funding from Pharmacyclics LLC, an AbbVie Company. J.Ra. reports stock or other ownership with ADC Therapeutics (self) and AstraZeneca (spouse); honoraria from ADC Therapeutics, Bristol Myers Squibb, and Takeda; a consulting/advisory role and speakers bureau for ADC Therapeutics and Takeda; and research funding from Takeda. S.B. reports a consulting/advisory role for and travel/accommodations/expenses from AbbVie, Gilead, Janssen, Roche, and Takeda. D.M. reports stock or other ownership with Johnson & Johnson, Merck, Pfizer, Regeneron, Roche, and Vertex Pharma. J.M. reports honoraria from Curio, Kyowa, OneView, Physicians' Education Resource, Seagen, and Targeted Oncology; a consulting/advisory role for ADC Therapeutics, Alexion, Bayer, BeiGene, Bristol Myers Squibb, Debiopharm, Epizyme, Fosun Kite, Genmab, Gilead/Kite Pharma, Innovent, Janssen, Juno/Celgene, Kyowa, Karyopharm, Morphosys/Incyte, Novartis, Pfizer, Seagen, Servier, and Pharmacyclics LLC, an AbbVie Company; research funding from Bayer, Celgene, Genentech, Gilead/Kite Pharma, Incyte, Janssen, Merck, Millennium, Portola, Seagen, and Pharmacyclics LLC, an AbbVie Company; and speakers bureau for Acrotech/Aurobindo, AstraZeneca, Bayer, BeiGene, Celgene/Bristol Myers Squibb, Genentech/Roche, Gilead/Kite Pharma, Janssen, Kyowa, Seagen, Verastem, and Pharmacyclics LLC, an AbbVie Company. J.P. reports employment and stock or other ownership with AbbVie. E.S.-G. reports employment and stock or other ownership with AbbVie. K.E. reports employment with Pharmacyclics LLC, an AbbVie Company; and stock or other ownership with AbbVie. J.K.N. reports employment and stock or other ownership with AbbVie. A.G. reports a leadership position with COTA Healthcare, Genomic Testing Cooperative LCA, and Resilience; stock or other ownership with Alloplex, COTA Healthcare, Genomic Testing Cooperative LCA, Resilience, and Vincerx; a consulting/advisory role for Alloplex, AstraZeneca, Bristol Myers Squibb, Celgene, Clinical Advances H&O, Elsevier's Practice Update Oncology, Gilead, Hoffmann-La Roche, Janssen, Kite Pharma, Medscape, Michael J Hennessey Associates, MorphoSys, Novartis, Onclive Peer Exchange, Physicians Education Resource, Roswell Park, Vincerx, and Xcenda-Amerisource; research funding from Acerta, AstraZeneca, Bristol Myers Squibb, Genentech, Hoffmann-La Roche, Infinity, Janssen, Karyopharm, Kite Pharma, MorphoSys, Seagen, Verastem, and Pharmacyclics LLC, an AbbVie Company; travel/accommodations/expenses from Alloplex, AstraZeneca, Bristol Myers Squibb, Celgene, Clinical Advances H&O, COTA Healthcare, Elsevier's Practice Update Oncology, Genomic Testing Cooperative LCA, Gilead, Hoffmann-La Roche, Janssen, Kite Pharma, Medscape, Michael J Hennessey Associates, MorphoSys, Novartis, Onclive Peer Exchange, Physicians Education Resource, Roswell Park, Resilience, Vincerx, and Xcenda-Amerisource; and other relationship with Acerta, Alloplex, AstraZeneca, Bristol Myers Squibb, Celgene, Clinical Advances H&O, COTA Healthcare, Elsevier's Practice Update Oncology, Genentech, Genomic Testing Cooperative LCA, Gilead, Hoffmann-La Roche, Infinity, Janssen, Karyopharm, Kite Pharma, Medscape, Michael J Hennessey Associates, MorphoSys, Novartis, Onclive Peer Exchange, Physicians Education Resource, Resilience, Roswell Park, Seagen, Verastem, Vincerx, Xcenda-Amerisource, and Pharmacyclics LLC, an AbbVie Company.