Plerixafor Overcomes Lenalidomide-Associated Stem Cell Collection Failure and Affects Collected Myeloid and Erythroid Progenitors

High-dose chemotherapy followed by autologous hematopoietic cell transplantation (auto-HCT) remains standard of care for transplant-eligible multiple myeloma (MM) patients (pts). MM frontline therapy typically includes lenalidomide (LEN). However, studies have indicated that LEN-containing regimens are associated with an increase in peripheral blood stem cell (PBSC) collection failure. Since most health insurance carriers do not reimburse for PBSC collection if there is no intent to proceed with auto-HCT soon after collection, a common current practice is early auto-HCT after a few cycles of LEN-containing regimen. This may prevent a subset of pts from achieving the deepest possible response prior to transplant. Recently, plerixafor has been used sporadically to ameliorate the suppressive effect of LEN on PBSC collection, however its effect on collected graft composition is unknown. Here, we examine the influence of plerixafor on PBSC mobilization, graft composition, and auto-HCT outcomes.

Methods

Pts who underwent auto-HCT between 2007 and 2016 at our institution were included. After excluding pts without complete progenitor cell assays, 94 pts formed the final analysis set. The primary end point was PBSC collection failure, defined as the inability to collect at least 5×10^6 CD34+ cells/kg on first apheresis attempt. Secondary endpoints were frequency, in-vitro proliferation, and differentiation capability of hematopoietic progenitors. Granulocyte-Monocyte Colony-Forming Units (CFU-GM) and Burst-Forming Erythroid Units (BFU-E) colonies were scored after 14 days of incubation. Effects of baseline and treatment variables on PBSC collection failure were examined by logistic regression. Significant variables were entered in a multivariate regression model.

Results

PBSC mobilization was achieved with G-CSF and cyclophosphamide (21 pts), G-CSF alone (8 pts), or with G-CSF and plerixafor (65 pts). Pts that received LEN-containing regimens as the immediate line of therapy before collection (LENpos, N=51) were compared to those who did not (LENneg, N=43). Median number of LEN cycles was 4 (range 1-13). 15 pts (16%) had day 1 collection failure with no difference between LENpos and LENneg groups (17% vs. 14%, respectively; P=0.392). Only 1 pts (1.1%) failed final collection. Collection days and median number of collected CD34+ cells were similar in both groups. Older age (OR: 1.85, 95% CI: 1.11-2.54, P=0.001), lower platelets on day of stem cell collection (OR: 1.87, 95% CI: 1.09-2.98, P=0.021), and lack of plerixafor use for PBSC mobilization (OR: 1.96, 95% CI: 1.11-3.52, P<0.001) were risk factors associated with worse stem cell collection in univariate analysis (Table 1). All three parameters detected by univariate analysis retained statistical negative predictive significance. LEN exposure did not affect the collection failure rate (OR: 1.15, 95% CI: 0.81-1.36, P=0.356). There was no difference between LENpog and LENneg groups in median ratio of CFU-GM/total nucleated cells (TNC) (10.5 vs. 11.7 10^-4, P=0.381) neither BFU-E/TNC (7.2 vs. 7.9 10^-4, P= 0.253), indicating similar LEN effect on collected myeloid and erythroid progenitors. The number of collected CFU-GM and BFU-E correlated with collected TNC in both groups (LENpos: R2:0.400, P=0.031, LENneg: R2: 0.405, P=0.001; and LENpos: R2:0.357, P=0.009, LENneg: R2: 0.292, P=0.001; respectively, Figure 1). However there were no difference between LENpos and LENneg group. LENpos pts that did not use plerixafor had significantly lower collected CFU-GM and BGU-E compared to the remainder of pts (P=0.003 and P=0.021, respectively; Figure 3). Mean time to neutrophil and platelet engraftments were similar in both groups (Figure-2). There was one platelet engraftment failure in the LENneg group. There was no detected difference in progression-free survival between the two groups (3-year PFS rate: 71% vs. 74%, HR: 0.91, CI: 0.72-1.16, p=0.27).

Conclusions

In our cohort of heavily pre-treated pts, the length of LEN usage prior to PBSC collection did not affect PBSC collection, graft quality or engraftment when plerixafor was added to the mobilization regimen, suggesting plerixafor may overcome potential deleterious effects of LEN on PBSC collection. The impact of LEN on PBSC collection and transplantation needs further study in prospective clinical trials.

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