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Letters to the Editor
Stem cell yield and transplantation in transplant-eligible newly diagnosed multiple myeloma patients receiving daratumumab plus bortezomib/thalidomide/dexamethasone in the phase III CASSIOPEIA study
High-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) is the standard of care for transplant-eligible patients with newly diagnosed multi- ple myeloma (NDMM).1,2 An adequate stem cell yield is essential for timely hematopoietic reconstitution after ASCT.3 Daratumumab is a human immunoglobulin (Ig) Gk monoclonal antibody targeting CD38 with a direct on-tumor4-6 and immunomodulatory mechanism of action.7-9 Multiple studies have demonstrated the clinical benefits of adding daratumumab to standard-of-care reg- imens or as monotherapy across lines of therapy in mul- tiple myeloma.10
The phase III CASSIOPEIA study investigated daratu- mumab plus the standard-of-care regimen bortezomib/thalidomide/dexamethasone (D-VTd) versus bortezomib/thalidomide/dexamethasone (VTd) in ASCT- eligible patients with NDMM.11 In part 1 of the study, patients received induction, ASCT, and consolidation therapy, which was followed by part 2 of the study where patients with a partial response or better after consolida- tion were re-randomized to receive maintenance therapy
or observation. Here we report stem cell yield/harvest and transplantation results in part 1 of CASSIOPEIA.
The study design and eligibility criteria of CASSIOPEIA have been previously reported (clinicaltrials gov. Identifier: NCT02541383) (Figure 1).11 Briefly, eligible patients were 18 to 65 years of age, had NDMM, had an Eastern Cooperative Oncology Group performance status of 0 to 2, and were candidates for HDT and ASCT. Major exclu- sion criteria included the following: hemoglobin concen- tration <7.5 g/dL; absolute neutrophil count <1.0×109/L; platelet count ≤50×109/L (or <70×109/L if <50% of bone marrow nucleated cells were plasma cells); aspartate aminotransferase and alanine aminotransferase levels >2.5 times the upper limit of normal (ULN); total bilirubin level >1.5 times ULN; calculated creatinine clearance <40 mL/min; corrected serum calcium concentration >14 mg/dL (3.5 mmol/L); primary amyloidosis, monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, solitary plasmacytoma, or Waldenström macroglobulinemia; previous systemic ther- apy or stem cell transplantation for any plasma cell dyscrasia; and grade ≥2 peripheral neuropathy or grade ≥2 neuropathic pain. All patients provided written informed consent; the trial was approved by Institutional Review Board/ethics committees at each site and was conducted in accordance with the Declaration of Helsinki, Good Clinical Practices, and applicable regulatory requirements.
Following induction, patients underwent stem cell
Figure 1. CONSORT diagram for the CASSIOPEIA study. The study flow diagram is shown for the CASSIOPEIA study from first randomization through completion of autologous stem cell transplant. The daratumumab group received daratumumab/bortezomib/thalidomide/dexamethasone; the control group received bortezomib/thalidomide/dexamethasone. Other: includes patient withdrawal, investigator decision, and others. aReasons for discontinuation are not mutually exclusive. bOne patient had successful CD34+ stem cell collection without any previous mobilization treatment.
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