Impact of Clinical Parameters and Induction Regimens on Peripheral Blood Stem-Cell Mobilization and Collection in Multiple Myeloma Patients

Abstract

Introduction: High-dose chemotherapy (HDCT) followed by autologous blood stem-cell transplantation (ABSCT) remains the standard consolidation therapy for newly diagnosed eligible multiple myeloma (MM) patients. As a prerequisite, peripheral blood stem cells (PBSCs) must be mobilized and collected by leukapheresis (LP). Many factors can hamper PBSC mobilization/collection. Here, we provide a comprehensive multiparametric assessment of PBSC mobilization/collection outcome parameters in a large cohort. Methods: In total, 790 MM patients (471 [60%] male, 319 [40%] female) who underwent PBSC mobilization/collection during first-line treatment were included. Evaluated PBSC mobilization/collection outcome parameters included the prolongation of PBSC mobilization, plerixafor administration, number of LP sessions, and overall PBSC collection goal/result. Results: 741 (94%) patients received cyclophosphamide/adriamycin/dexamethasone (CAD) and granulocyte-colony-stimulating factor (G-CSF) mobilization. Plerixafor was administered in 80 (10%) patients. 489 (62%) patients started LP without delay. 530 (67%) patients reached the PBSC collection goal at the first LP session. The mean overall PBSC collection result was 10.3 (standard deviation [SD] 4.4) × 106 CD34+ cells/kg. In a multiparametric analysis, variables negatively associated with PBSC mobilization/collection outcomes were female gender, age >60 years, an advanced ISS stage, and local radiation pre-/during induction, but not remission status postinduction. Notably, the identified risk factors contributed differently to each PBSC mobilization/collection outcome parameter. In this context, compared to all other induction regimens, lenalidomide-based induction with/without antibodies negatively affected only the number of LP sessions required to reach the collection goal, but no other PBSC mobilization/collection outcome parameters. In contrast, the probability of reaching a high collection goal of ≥6 × 106 CD34+ cells/kg body weight was higher after lenalidomide-based induction compared to VCD/PAD or VAD – taking into account – that a higher G-SCF dosage was given in approximately one-third of patients receiving lenalidomide-based induction with/without antibodies. Conclusion: Considering the identified risk factors in the clinical setting can contribute to optimized PBSC mobilization/collection. Moreover, our study demonstrates the necessity for a differentiated evaluation of PBSC mobilization/collection outcome parameters.

Multiple Myeloma: The Role of Autologous Stem Cell Transplantation in the Era of Immunotherapy

“…Despite the lower yields and increased plerixafor use in the daratumumab-containing regimens in the NDMM setting across the MASTER, GRIFFIN, and CASSIOPEIA trials, the integration of daratumumab into the PI-IMIds triplet therapy did not negatively affect the feasibility and safety of conducting ASCT or hinder successful engraftment. Several retrospective clinical trials have described HSC mobilization and collection in patients receiving daratumumab-based induction regimens [44][45][46].…”

Identifying Candidates for Effective Utilization of Stored Autologous PBSCs in Salvage Transplantation for Multiple Myeloma: Who Benefits Most?

“…This method required invasive bone marrow aspirations and was associated with limited yields. Consequently, it was gradually supplanted by the use of peripheral blood stem cells (PBSCs), which could be collected via leukapheresis, offering higher stem cell yields and a less invasive procedure [ 3 ].…”

“…Despite the availability of stored PBSC grafts, salvage ASCT is not always performed due to various factors such as deterioration in performance [ 12 ], status, or therapy-related comorbidities. Furthermore, a cost utilization analysis conducted in 2013 revealed that a substantial proportion of patients had PBSC products remaining unused in prolonged cryopreservation after the initial ASCT [ 3 , 13 ]. This surplus stemmed from the estimated cost of collecting and storing PBSCs beyond that required for a single ASCT, accounting for approximately one-third of total costs.…”

Stem Cell Mobilization, Collection, and Processing

“…Regarding patients with multiple myeloma, Jantunen et al comprehensively analyzed current mobilization strategies [1]. The impact of clinical parameters and induction regimens on peripheral blood stem cell (PBSC) mobilization in a large cohort of multiple myeloma patients has been evaluated by Sauer and colleagues [2]. In a more specific approach, Sauer et al [3] assessed in a second study the effectiveness of autologous stem cell collection after daratumumab-VTD versus VCD.…”