Daratumumab, cyclophosphamide, bortezomib, and dexamethasone for multiple myeloma: final results of the LYRA study

Abstract

In the primary analysis of LYRA, daratumumab + cyclophosphamide/bortezomib/dexamethasone (DARA + CyBorD) was effective and well tolerated in newly diagnosed multiple myeloma (NDMM) and relapsed multiple myeloma (RMM). We report the final analysis of LYRA (median months of follow-up: NDMM, 35.7; RMM, 35.3) after all patients completed study therapy, were followed for 36 months, or discontinued. Patients received DARA + CyBorD induction, autologous stem cell transplant (if eligible), and 12 months of daratumumab maintenance. Eighty-seven NDMM patients enrolled, 39 underwent transplant, and 63 completed maintenance. Rates of complete response or better were 48.7% and 29.8% for NDMM transplant and NDMM non-transplant patients, respectively, and 36-month progression-free survival rates were 69.3% and 72.6%. Grade 3/4 treatment-emergent adverse events occurred in 61.6% of NDMM patients. Efficacy and safety data are also reported for the smaller RMM cohort (n = 14). DARA + CyBorD followed by daratumumab maintenance was well tolerated and achieved deep, durable responses in NDMM and RMM.

Keywords:

• Daratumumab
• newly diagnosed multiple myeloma
• CyBorD

Data sharing statement

The data sharing policy of Janssen Pharmaceutical Companies of Johnson & Johnson is available at https://www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at http://yoda.yale.edu.

Acknowledgments

The authors thank the patients who volunteered to participate in this trial, their families, and the staff members at the trial sites who cared for them. J.M.B. and R.M.R. contributed to study design and data acquisition; Y.L, K.Q., M.Q., and T.S.L. contributed to study design; H.Y., J.M., E.F., W.I.B., M.N., D.S., and D.H. contributed to data acquisition; and all authors contributed to data analysis or interpretation, reviewed the manuscript, approved the final version, decided to publish this report, and vouch for the data accuracy and completeness. NCCN makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way.

Disclosure statement

H.Y. has served on a speakers bureau for Janssen, AstraZeneca, BeiGene, Amgen, Sanofi Genzyme, Pharmacyclics, and Karyopharm Therapeutics; and holds equity ownership in Karyopharm Therapeutics.

J.M. has served on a speakers bureau for Janssen and AstraZeneca.

E.F. has served as a consultant and/or participated in a Data Safety Monitoring Board or Advisor Board for Amgen, Celgene, Janssen, Juno Therapeutics, AbbVie, Adaptive Biotechnologies, AstraZeneca, Cardinal Health, GlaxoSmithKline, Karyopharm, Sanofi Genzyme, Takeda, and Kite/Gilead.

W.I.B. has served as a consultant or in an advisory role for Amgen, Celgene, and Janssen; has served on a speakers bureau for Amgen, Celgene, Janssen, and Takeda; has provided expert testimony for Celgene and Takeda; has received honoraria from Amgen, Celgene, Janssen, and Takeda; and has received research funding from Acetylon Pharmaceuticals, Bristol Myers Squibb, Celgene, Karyopharm Therapeutics, Merck, Amgen, and Sanofi.

J.M.B. has served as a consultant or in an advisory role for Genentech/Roche, AbbVie, Seattle Genetics, Bayer, AstraZeneca, Adaptive Biotechnologies, Verastem, MorphoSys, Kura Oncology, Epizyme, BeiGene, Kymera, TG Therapeutics, X4 Pharmaceuticals, and Novartis; and served on a speakers bureau for Seattle Genetics and BeiGene.

M.N. has served as a consultant or in an advisory role for Celgene and Bristol Myers Squibb and has served on a speakers bureau for Bristol Myers Squibb.

D.S. has nothing to disclose.

P.B. is an employee of Janssen.

D.H. and Y.L. were employees of Janssen at the time of the study and have equity ownership in Johnson & Johnson.

K.S.G., T.S.L., K.Q., and M.Q. are employees of Janssen and have equity ownership.

R.M.R. has served as a consultant or in an advisory role for Amgen, Bristol Myers Squibb/Celgene, Coherus BioSciences, Fresenius Kabi, and Takeda; participated in a Data Safety Monitoring Board for CARsgen Therapeutics; and has equity ownership in McKesson Specialty Health.

Additional information

Funding

This study (ClinicalTrials.gov Identifier: NCT02951819) was supported by Janssen Oncology. Medical writing and editorial support were provided by Austin Horton, PhD, and Charlotte D. Majerczyk, PhD, of Cello Health Communications/MedErgy, and were funded by Janssen Global Services, LLC.