Safety and efficacy of daratumumab in combination with bortezomib and dexamethasone in Japanese patients with relapsed or refractory multiple myeloma
Daratumumab in combination with bortezomib and dexamethasone (DVd) has demonstrated longer progression-free survival than combination of bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma (RRMM). In this multicenter, open-label, phase-1 study, the safety, efficacy, and pharmacokinetics (PK) of DVd were evaluated in Japanese patients with RRMM. Eight patients with RRMM aged between 54 and 82 years were enrolled and treated with DVd regimen. Primary endpoints were tolerability and safety. Secondary endpoints were overall response rate (ORR), very good partial response (VGPR) or better, complete response (CR) or better, time to response (TTR), PK, and immunogenicity. All patients (n = 8) experienced Grade ≥ 3 treatment-emergent adverse events (TEAE), with thrombocytopenia (n = 6, 75%) being the most frequent. Mild Grade ≤ 2 infusion-related reactions were reported in five patients. Serious TEAEs were herpes zoster, nasopharyngitis, and prostate cancer (n = 1 each). Three dose-limiting toxicities were observed in two patients. No death or disease progression was reported as of the study cut-off date. ORR was 100% (2 CRs or better, 2 VGPRs, 4 PRs). The median TTR was 0.9 months. PK profiles were comparable to previous studies. The DVd regimen showed acceptable safety with favorable efficacy in Japanese patients with RRMM.
Clinical trial registration number
KeywordsDaratumumab Efficacy Multiple myeloma Safety Tolerability
Dr. Aoki had primary role in the study design, analysis and data interpretation. Drs Iida, Ichinohe, Shinagawa, Suzuki and Takezako were involved in study design, data interpretation and also involved as investigators. All authors contributed to the development of the manuscript and approved the final manuscript for submission. All authors had full access to all the data in the study and had final responsibility for the decision to submit for publication.
- 1.Raedler LA. Darzalex (Daratumumab): first anti-CD38 monoclonal antibody approved for patients with relapsed multiple myeloma. Am Health Drug Benefit. 2016;9(Spec Feature):70–3.Google Scholar
- 6.Sonneveld P, Goldschmidt H, Rosiñol L, Bladé J, Lahuerta JJ, Cavo M, et al. Bortezomib-based versus nonbortezomib-based induction treatment before autologous stem-cell transplantation in patients with previously untreated multiple myeloma: a meta-analysis of phase III randomized, controlled trials. J Clin Oncol. 2013;31:3279–87.CrossRefPubMedGoogle Scholar
- 12.Approved drugs—daratumumab (DARZALEX). https://www.fda.gov/Drugs/informationOnDrugs/ApprovedDrugs/ucm530249.htm. Accessed 17 May 2017.
- 13.Janssen Biotech Inc. DarzalexTM (daratumumab): prescribing information. 2016. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/761036s004lbl.pdf. Accessed 17 May 2017.
- 18.de Weers M, Tai Y-T, van der Veer MS, Bakker JM, Vink T, Jacobs DCH, et al. Daratumumab, a novel therapeutic human CD38 monoclonal antibody, induces killing of multiple myeloma and other hematological tumors. J Immunol. 2011;186:1840–8.Google Scholar
- 22.Mateos M-V, Moreau P, Comenzo R, Bladé J, Benboubker L, de La Rubia J, et al. An open-label, multicenter, phase 1B study of daratumumab in combination with pomalidomide-dexamethasone and with backbone regimens in patients with multiple myeloma. European Hematology Association; 2015. Abstract p. 275.Google Scholar
- 23.Endell J, Samuelsson C, Boxhammer R, Strauss S, Steidl S. Effect of MOR202, a human CD38 antibody, in combination with lenalidomide and bortezomib, on bone lysis and tumor load in a physiologic model of myeloma. J Clin Oncol. 2011;29: 2011 (suppl; abstr 8078) suppl; abstr 8078. http://meetinglibrary.asco.org/content/80499-102. Accessed 17 May 2017.