Impact of Lenalidomide on Hematopoietic Myeloid and Erythroid Progenitors: Peripheral Stem Cell Collection May Not be Affected (2017)

Triplet regimens that include the immunomodulatory agent lenalidomide (LEN) have emerged as standard-of-care frontline therapy for multiple myeloma. Peripheral blood stem cell collection (PBSC) occurs frequently after only a few cycles of LEN, mostly due to reported deleterious effect of this agent on collections. This approach prevents a subset of patients (pts) from achieving the deepest possible response prior to transplant. Plerixafor antagonizes binding SDF-1 to its cognate receptor CXCR4, results in rapid mobilization of hematopoietic stem cells, and may ameliorate the suppressive effect of LEN on PBSC. Here, we examined the effect of LEN before PBSC collection on early erythroid, Burst-forming Erythroid Unit (BFU-E), and myeloid progenitors, Granulocyte-Monocyte Colony-forming Units (CFU-GM), and its effect on autologous stem cell transplant (ASCT) outcomes. Methods: Ninety four pts who underwent first ASCT from 2007 to 2014 at our institution were included. Median age was 59 years old at the time of ASCT. Fifty three (56%) and 40 (42%) pts achieved partial response and very good partial response or better, respectively, before undergoing ASCT. Median number of prior regimens were 2 (1-6). Median time from diagnosis to ASCT was 11.7 months. All pts underwent leukapheresis using the COBE Spectra cell separator. Twenty one pts were collected after Cytoxan and G-CSF, 8 with G-CSF alone and 65 with G-CSF and Plerixafor. Median number of collections was 2 (range, 1-4). Pts that received LEN containing regimens as the immediate line of therapy before PBSC collection (LENpos, n = 51) were compared to those who did not (LENneg, n = 43). Pts that received pomalidomide-containing regimen before PBSC were excluded. Result: Mean number of collection days was similar in LENpos vs. LENneg group (2.11 vs. 2, P = .47). Median collected CD34 was 8.6 vs. 11.3 in LENpos and LENneg group with no significant difference (P = .12). Mean time to neutrophil engraftment was not different between LENpos vs. LENneg (10. 58 vs. 10.55, days P = .45). Mean time to platelet engraftment was also similar (19.3 vs. 21.7 days, P = .19). There was one platelet engraftment failure in LENneg group. There was a significant correlation between collected TNC and BFU-E as well as TNC and CFU-GM, however there was no significant difference between LENpos and LENneg group. The overall rate of day 1 collection failure was 14.2% with no statistically significant difference between LENpos and LENneg groups (Median: 13.5% vs. 14.6%; P = .39). There was no detected difference in progression-free survival. Conclusion: In this cohort of heavily pretreated pts, use of LEN prior to PBSC collection did not affect stem cell collection, graft quality or engraftment. High usage of Plerixafor may have overcome the deleterious effect of LEN. The impact of LEN on stem cell collection and transplantation should be evaluated in prospective clinical trials (Figure 1, Figure 2, Figure 3).Figure 2Comparison of Neutrophil (A) and Platelet (B) engraftment in LENpos vs. LENneg group.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Figure 3Progression Free Survival after transplant in LENpos vs. LENneg group.View Large Image Figure ViewerDownload Hi-res image Download (PPT)