Tafasitamab combined with idelalisib or venetoclax in patients with CLL previously treated with a BTK inhibitor

Abstract

Patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL) whose treatment failed with a Bruton’s tyrosine kinase inhibitor have poor outcomes. We investigated tafasitamab plus idelalisib (cohort A) or venetoclax (cohort B) in this patient population in a phase II study (NCT02639910). In total, 24 patients were enrolled (cohort A: n = 11, median time on study, 7.4 months; cohort B: n = 13, median time on study, 15.6 months). The most common treatment-emergent adverse event (TEAE) in cohort A was anemia (63.6%) and in cohort B was infusion-related reaction (53.8%). The most common severe TEAE was neutropenia (cohort A: 45.5%; cohort B: 46.2%). The best overall response rate was 90.9% (cohort A) and 76.9% (cohort B). Undetectable minimal residual disease in peripheral blood was achieved in 2/8 patients (cohort A) and 6/7 patients (cohort B). Overall, these results suggest that anti-CD19 antibody-based combinations may be important in the treatment of patients with CLL.

Keywords:

• Relapsed/refractory chronic lymphocytic leukemia
• tafasitamab
• anti-CD19 antibody
• idelalisib
• venetoclax
• phase II study

Disclosure statement

P.S. has acted as a consultant for, received honoraria from, and provided paid expert testimony for AstraZeneca, AbbVie, Janssen, Gilead, Roche, MSD, BMS, CTI, Incyte, and Takeda-Millennium within the past 2 years and has also received research funding from Roche Diagnostics. W.J. has acted as a consultant for AstraZeneca, Debiopharm, Janssen, Gilead, and Roche within the past 2 years and has received research funding from Morphosys, Acerta, AstraZeneca, Janssen, BeiGene, Bayer, Celltrion, Debiopharm, Epizyme, Merck, MEI Pharma, Servier, Roche, and TG therapeutics. R.G. has acted as a consultant within the past 2 years and been a member of the board of directors or its advisory committees for each of Celgene, Novartis, Roche, BMS, Takeda, AbbVie, AstraZeneca, Janssen, MSD, Merck, Gilead, and Daiichi Sankyo. R.G. has also received research funding from Celgene, Merck, Takeda, AstraZeneca, Novartis, Amgen, BMS, MSD, Sandoz, Gilead, and Roche in addition to receiving honoraria from Celgene, Roche, Merck, Takeda, AstraZeneca, Novartis, Amgen, BMS, MSD, Sandoz, AbbVie, Gilead, and Daiichi Sankyo. V.V. has acted as a consultant for AbbVie and Gilead within the past 2 years. J.M.M. has acted as a consultant for AbbVie and Janssen within the past 2 years. M.M. has acted as a consultant for AbbVie, Janssen, Verastem, and Astra Zeneca within the past 2 years in addition to receiving honoraria from AbbVie, Janssen, Gilead, Roche, and AstraZeneca together with research funding from Roche. T.M. has received honoraria from Roche, AbbVie, Janssen, Gilead, AstraZeneca, Novartis, and Alexion. S.S. has acted as a consultant within the past 2 years for and received research funding and honoraria from AbbVie, AstraZeneca, Celgene, Gilead, Hoffmann La-Roche, Janssen, and Novartis. F.S., M.D-H., J.W., W.B., and P.K. are employees of MorphoSys AG. C-M.W. has acted as a consultant within the past 2 years for and received research funding and honoraria from Hoffmann La-Roche, Janssen, Gilead, AbbVie, and MorphoSys. J.A.W. has acted as a consultant within the past 2 years for Janssen, Pharmacyclics, AbbVie, AstraZeneca, and Arqule and received research funding from Loxo and AbbVie. J.S. has received research funding from Sanofi, Novartis, and AbbVie and lecture fees from Roche, Janssen, AbbVie, and Gilead. P.N. has no conflicts of interest to declare.

Acknowledgements

We thank the patients and their families, clinical researchers, and their teams and hospitals that have participated in this study. We would also like to thank Guido Würth and Rainer Boxhammer of MorphoSys for their contributions to this manuscript. Medical writing assistance was provided by Ross Jarratt at Syneos Health and funded by MorphoSys AG.

Notes

1 About tafasitamab: Tafasitamab is a humanized Fc-modified cytolytic CD19-targeting monoclonal antibody. In 2010, MorphoSys licensed exclusive worldwide rights to develop and commercialize tafasitamab from Xencor, Inc. Tafasitamab incorporates an XmAb^® engineered Fc domain, which mediates B-cell lysis through apoptosis and immune effector mechanism including antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). In January 2020, MorphoSys and Incyte entered into a collaboration and licensing agreement to further develop and commercialize tafasitamab globally. Following accelerated approval by the U.S. Food and Drug Administration in July 2020 for tafasitamab in combination with lenalidomide for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from low grade lymphoma, who are not eligible for autologous stem cell transplant, tafasitamab is being co-commercialized by MorphoSys and Incyte in the United States. Incyte has exclusive commercialization rights outside the United States. XmAb^® is a trademark of Xencor, Inc.

Additional information

Funding

The study was designed and sponsored by MorphoSys AG.