Peri-transplant Stem Cell Kinetics After Daratumumab-Based Induction in Patients with Multiple Myeloma: Response to Mish
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CORRESPONDENCE
Peri-transplant Stem Cell Kinetics After Daratumumab-Based Induction in Patients with Multiple Myeloma: Response to Mishra et al Ankur Jain1
Received: 22 October 2019 / Accepted: 12 March 2020 Ó Indian Society of Hematology and Blood Transfusion 2020
Dear editor, Daratumumab (DARA), an IgG-kappa monoclonal antibody against CD38, has changed the therapeutic paradigm of Multiple Myeloma (MM). Frontline DARA-based combinations result in rapid, deeper, and sustained responses, including minimal residual disease (MRD)negativity. Since hematopoietic stem cells (HSC) express CD38, frontline use of DARA could theoretically affect peri-autologous stem cell transplant (ASCT) outcomes, including both HSC mobilization and post-ASCT hematopoietic reconstitution. We intend to review the existing data on effect of DARA on peri-ASCT outcomes, and comment on article by Mishra et al. recently published in Indian Journal of Hematology and Blood Transfusion [1]. Ma et al. studied the in-vitro effect of DARA including its binding, complement-dependent cytotoxicity (CDC), and colony-forming unit (CFU) capacity on mobilized CD34? HSC. DARA neither resulted in cytotoxicity, nor affected the CFU-capacity of HSC, possibly because of low density of CD38 on HSC [2]. Clinically, DARA has been combined with frontline regimens in both non-randomized [cyclophosphamide-bortezomib-dexamethasone (CyBorD), bortezomib-lenalidomide-dexamethasone (VRD), carfilzomib-lenalidomide-dexamethasone (KRD)], and randomized [bortezomib-thalidomide-dexamethasone (VTD)] fashion in transplant-eligible MM patients [3–6]. Median HSC dose collected after frontline DARA-CyBorD, DARA-KRD, and DARA-VTD was 5.0 9 106/kg, & Ankur Jain [email protected] 1
Department of Hematology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi 110029, India
10.6 9 106/kg, and 6.3 9 106/kg, respectively [3–6]. HSC data of DARA-VRD from Griffin trial is awaited [4]. Although DARA-treated patients required higher number of plerixafor and apheresis sessions, median HSC dose was almost comparable to the respective control arms (historical control for CyBorD and KRD; randomized control for VTD) [3–6]. Moreover, HSC dose has been correlated with time to platelet engraftment (PE) but not neutrophil engraftment (NE) after peripheral blood-ASCT [7]. Therefore, NE and PE are not expected to be affected by DARA-based induction regimens. In support for this, an updated analysis of CASSIOPEIA suggested that the time to NE and PE were similar for DARA-VTD and VTD arms (13 days vs. 13 days, and 14 days vs. 12 days). Authors concluded that DARA-based induction is safe, feasible, and did not affect the ASCT-outcomes, including hematopoietic reconstitution [8]. Definitive conclusions regarding effect of DARA on peri-ASCT outcomes could only be drawn by comparing DARA-chemotherapy with the same chemotherapy backbone without DARA in a prospective randomized control trial (RCT). CASSIOPEIA is the only RCT available till date, while results of Griffin and PERSEUS trials (
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