Chemotherapy-Based Stem Cell Mobilization Does Not Result in Significant Paraprotein Reduction in Myeloma Patients in the Era of Novel Induction Regimens
Authors: Oyekunle Anthony , Shumilov Evgenii , Kostrewa Philippe , Burchert Andreas , Wuchter Patrick , Bacher Ulrike , Wulf Gerald , Kroeger Nicolaus 
Published: October 2019

Abstract
Introduction: The introduction of novel induction therapies in the management of multiple myeloma (MM) has led to markedly improved remission rates, resulting in calls to revisit the need for chemotherapeutic agents in the mobilization of CD34+stem cells (SC) for autologous stem cell transplantation (ASCT). We examined the additional benefit over steady-state mobilization with G-CSF alone with regard to optimization of the myeloma remission status and morbidity resulting from chemotherapeutic SC mobilization.
Methods: This retrospective multicenter study reviewed 236 consecutive MM pts from4 German centers: Hamburg, Goettingen, Marburg and Heidelberg, who had 1stASCT from 2009 to 03/2016 following chemotherapy-based stem cell mobilization. The median age was 59 (range, 36-75) years, with 152 (64.4%) males. Paraproteins were IgG (n=120, 54.1%), IgA (n=55, 24.8%), or light chains (LC) only (n=47, 21.2%), with LC being mostly kappa (131/221, 59.3%). Response was assessed according to International Myeloma Working Group (IMWG) criteria, and was based on the reduction in free LC and heavy chain (HC) levels before and after chemo-mobilization.
Results: 225 (95.3%) pts had received at least 3 cycles of either bortezomib- (n=222, 94.1%) or lenalidomide-based (n=19, 8.1%) induction regimens. Of the 190 pts for which post-induction remission status was known, 170 (89.5%), 73 (38.4%) and 15 (7.9%) had achieved partial remission (PR), very good PR (VGPR), and complete remission (CR), respectively. SC were mobilized with G-CSF combined with cyclophosphamide- (n=212, 93.4%) or etoposide-based (n=15, 6.6%) chemotherapy regimens. There was no significant change in the mean serum free LC and HC levels of pts pre- and post-chemomobilization (Table 1). For pts with kappa myelomas, the mean kappa/lambda ratio (KLr) was 211.1±679.1 before and 360.0±1250.0 post-chemomobilization (P=0.1165); and for lambda myeloma, mean KLr was 0.504±1.143 and 0.810 ± 2.352, respectively (P=0.1348). Analysis of pts with different myeloma subtypes according to the HC and LC concentrations pre- and post-chemomobilization also showed no significant changes. Only 7(3.7%) pts newly attained PR or VGPR following chemomobilization, whereas the remaining pts showed no significant change in the myeloma remission status as compared to the pre-chemomobilization level. A total of 67 (28.4%) pts developed chemotherapy-related complications including neutropenic fever (n=40, 16.9%), sepsis (n=14, 5.9%) and others (n=43, 18.2%), resulting in nine hospital admissions (3.8%, mean=7.1 days).
Conclusion: Our study suggests that in spite of the significant morbidity associated with chemotherapy-based mobilization regimens, in the era of novel induction agents, only a minority of myeloma pts attain an improved remission status. Therefore, the value of incorporating additional chemomotherapy for SC mobilization as compared to G-CSF alone should be critically evaluated in the light of modern induction regimens used nowadays for myeloma pts.
Table. Mean serum free light chain (FLC) levels pre- and post-chemomobilization according to myeloma subtypes. *All values ± SD are given. Serum concentrations are in g/dL. FLC, free light chain; MM, multiple myeloma; k, kappa; l, lambda. aNegative values represent increases. Table. Mean serum free light chain (FLC) levels pre- and post-chemomobilization according to myeloma subtypes. / *All values ± SD are given. Serum concentrations are in g/dL. / FLC, free light chain; MM, multiple myeloma; k, kappa; l, lambda. / aNegative values represent increases.

Disclosures
Oyekunle: Novartis: Honoraria. Wuchter:Sanofi-Aventis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Hexal: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Kroeger:Sanofi: Honoraria, Research Funding.