PBSC Mobilization for Auto-HSCT in Myeloma: Growth Factors Vs Growth Factors + Chemotherapy
Authors: Ramdial Jeremy L. , Ma Junsheng , Milton Denai R. , Delgado Ruby , Bashir Qaiser , Srour Samer A. , Saini Neeraj , Nieto Yago , Hosing Chitra , Popat Uday R. , Murphy Regan , Lee Hans C. , Patel Krina K. , Manasanch Elisabet E. , Thomas Sheeba K. , Kaufman Gregory P. , Weber Donna M. , Orlowski Robert Z. , Champlin Richard E. , Qazilbash Muzaffar H. 
Published: November 2020

Background: Peripheral blood hematopoietic stem cell mobilization for autologous hematopoietic stem cell transplantation (auto-HSCT) in multiple myeloma (MM) can be achieved with either growth factors (GF) alone (filgrastim +/- plerixafor), or with chemotherapy (GF + chemo). When utilized, the chemotherapy regimens include single-agent cyclophosphamide (Cy), or combination regimens, including cyclophosphamide, vincristine or bortezomib, doxorubicin, dexamethasone (CVAD/CBAD) at our center. The optimal mobilization strategy, however, has yet to be established.

Methods: In this single center retrospective analysis, we identified 1,006 patients who received auto-HCT for MM between 2009 and 2015. This time-period was chosen to include patients who received auto-HCT after the availability of plerixafor. Patients were divided into 4 groups: G (filgrastim alone), G+P (filgrastim + plerixafor), Cy, and CVAD/CBAD. Plerixafor was mainly used "just-in-time", and not as planned therapy in accordance with our Departmental guidelines. Primary endpoints were CD34+ cell dose/kg collected, days to collect the target CD34+ cell dose, time to neutrophil engraftment (first of three consecutive days of peripheral blood neutrophil count of &gt;500 x 106/L), packed red blood cell (PBRC) and platelet transfusion requirement, duration of hospitalization, progression-free survival (PFS), and overall survival (OS).

Results: Patient characteristics are summarized in Table 1. There were 654 patients mobilized with G, 203 with G + P, 80 with Cy, and 69 with CVAD/CBAD. Patients mobilized with CVAD/CBAD were younger compared to the other three groups, were less likely to have achieved VGPR to induction, and more likely to have received a more intense preparative regimen (Table 1). Patients who received G alone, G+P, Cy, and CVAD/CBAD collected a median of 4.1 (0.7-12.2), 4.0 (1.8-11.1), 5.2 (2.2-19.2), and 5.6 (2.5-26.6) x106 CD34+ cells/kg [p&lt;0.001]. Median number of days to collect the target CD34+ cell dose of approximately 6x106 were, 3 (1-10), 5 (1-10), 2 (1-8), and 1 (1-8) for G, G+P, Cy and CVAD/CBAD groups, respectively [p&lt;0.001]. Median time to neutrophil engraftment was 11 days in all four groups, with the range being 8-15, 8-14, 8-13 and 9-13 for G, G+P, Cy and CVAD/CBAD respectively [p=0.021]. Median PRBC units transfused after auto-HCT were 1 (0-13), 1 (0-8), 2 (0-7), and 2 (0-9) for patients in G, G+P, Cy, and CVAD/CBAD groups, respectively [p&lt;0.001]. Median platelets units transfused after auto-HCT were 2 in all four groups. Median duration of hospitalization for auto-HCT was 17 (3-73), 18 (5-84), 18 (4-39), and 19 (5-34) days in G, G+P, Cy and CVAD/CBAD groups, respectively [p=0.003]. The 5-year [95% CI] PFS rates were 36.6% [32.9-40.7%], 38.5% [31.5-47%], 28.9% [20.0-41.5%], and 30.9% [21.5-44.3%] for G, G+P, Cy, and CVAD/CBAD groups, respectively. The 5-year [95% CI] OS rates were 71.3% [67.7-75.1%], 73.9% [67.3-81.2%], 67.6% [57.3-79.7%], and 61.7% [51.1-74.5%] for G, G+P, Cy, and CVAD/CBAD groups, respectively. On multivariable analysis, after adjusting for covariates including age, ISS stage, cytogenetic risk, and response to induction, there was no significant impact of mobilization approach on PFS or OS.

Conclusion: Approximately 85% of MM patients underwent PBSC mobilization with GF only (G or G+P). GF + chemo (Cy, CVAD/CBAD) was primarily used in patients with suboptimal response to induction, and allowed successful PBSC collection in this high-risk group. GF + chemo-based mobilization was associated with a higher CD34+ cell dose collection, without improving the time to neutrophil or platelet engraftment, PRBC or platelet transfusion requirement, or the duration of hospitalization.

Disclosures

Bashir: Purdue: Other: Advisory Board; StemLine: Research Funding; Acrotech: Research Funding; Takeda: Other: Advisory Board, Research Funding; Celgene: Research Funding; Amgen: Other: Advisory Board; KITE: Other: Advisory Board. Nieto:Secura Bio: Other: Grant Support; Astra Zeneca: Other: Grant Support; Novartis: Other: Grant Support; Affimed: Consultancy, Other: Grant Support. Hosing:NKARTA Inc.: Consultancy. Popat:Bayer: Research Funding; Novartis: Research Funding. Lee:Sanofi: Consultancy; GlaxoSmithKline: Consultancy, Research Funding; Genentech: Consultancy; Amgen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Genentech: Consultancy; Regeneron: Research Funding; Daiichi Sankyo: Research Funding; Takeda: Consultancy, Research Funding; Janssen: Consultancy, Research Funding. Patel:Bristol Myers Squibb: Consultancy, Research Funding; Oncopeptides: Consultancy; Poseida: Research Funding; Janssen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Cellectis: Research Funding; Precision Biosciences: Research Funding; Takeda: Consultancy, Research Funding; Nektar: Consultancy, Research Funding. Manasanch:Merck: Research Funding; Novartis: Research Funding; Quest Diagnostics: Research Funding; Adaptive Biotechnologies: Honoraria; GSK: Honoraria; Sanofi: Honoraria; BMS: Honoraria; Takeda: Honoraria; JW Pharma: Research Funding; Sanofi: Research Funding. Thomas:BMS: Research Funding; Ascentage: Membership on an entity's Board of Directors or advisory committees, Research Funding; X4 Pharma: Research Funding; Xencor: Research Funding; Pharmacyclics: Other: Advisory Boards; Genentech: Research Funding. Kaufman:Karyopharm: Honoraria; Bristol Myers Squibb: Research Funding; Janssen: Research Funding. Orlowski:Amgen, Inc., AstraZeneca, BMS, Celgene, EcoR1 Capital LLC, Forma Therapeutics, Genzyme, GSK Biologicals, Ionis Pharmaceuticals, Inc., Janssen Biotech, Juno Therapeutics, Kite Pharma, Legend Biotech USA, Molecular Partners, Regeneron Pharmaceuticals, Inc.,: Honoraria, Membership on an entity's Board of Directors or advisory committees; Laboratory research funding from BioTheryX, and clinical research funding from CARsgen Therapeutics, Celgene, Exelixis, Janssen Biotech, Sanofi-Aventis, Takeda Pharmaceuticals North America, Inc.: Research Funding; Founder of Asylia Therapeutics, Inc., with associated patents and an equity interest, though this technology does not bear on the current submission.: Current equity holder in private company, Patents & Royalties; Sanofi-Aventis, Servier, Takeda Pharmaceuticals North America, Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees; STATinMED Research: Consultancy. Champlin:Actinium: Consultancy; Johnson and Johnson: Consultancy; Omeros: Consultancy; Cytonus: Consultancy; DKMS America: Membership on an entity's Board of Directors or advisory committees; Genzyme: Speakers Bureau; Takeda: Patents & Royalties. Qazilbash:Bioclinica: Consultancy; Amgen: Research Funding; Janssen: Research Funding; Angiocrine: Research Funding; Bioline: Research Funding.