Impairment of Filgrastim-Induced Stem Cell Mobilization after Prior Lenalidomide in Patients with Multiple Myeloma

Abstract

Lenalidomide is an agent that has shown great activity in patients with multiple myeloma. However, studies have suggested that this drug negatively affects subsequent stem cell collection. To investigate whether lenalidomide impairs stem cell mobilization and collection, we reviewed data for patients with multiple myeloma who underwent mobilization with filgrastim. Predictors of mobilization failure were evaluated using logistic regression analysis. In 26 (9%) of 302 myeloma patients, stem cell mobilization failed. Mobilization failed in 25% of patients who had previously received lenalidomide, compared with 4% of patients who had not received lenalidomide (P < .001). In a multivariate analysis, prior lenalidomide use (odds ratio, 5.9; 95% CI, 2.4 to 14.3) and mobilization more than 1 year after diagnosis (odds ratio, 4.6; 95% CI, 1.9 to 11.1) were significantly associated with failed mobilization. Twenty-one of 26 patients in whom mobilization with filgrastim failed underwent remobilization with chemotherapy and filgrastim; in 18 (86%) of these 21 patients, stem cells were successfully mobilized and collected. In patients with multiple myeloma, prior lenalidomide therapy is associated with failure of stem cell mobilization with filgrastim. Remobilization with chemotherapy and filgrastim is usually successful in these patients.

Growth factor plus preemptive (‘just-in-time’) plerixafor successfully mobilizes hematopoietic stem cells in multiple myeloma patients despite prior lenalidomide exposure

“…Importantly, the detrimental effect of lenalidomide on HSC mobilization was associated with the extent of exposure, leading to the recommendation that transplant-eligible, lenalidomide-treated patients should undergo HSC collection Preemptive plerixafor in lenalidomide-treated patients LJ Costa et al during the first 6 months of therapy. Multiple subsequent and independent reports confirmed the detrimental effect of lenalidomide on mobilization, with mobilization failure rates up to 25% [8][9][10] along with a dose-dependent effect. 9,10 The use of CY plus growth-factor mobilization is often employed in MM with intent to obtain better CD34 þ yield while still providing anti-MM therapy, although the relevance of the latter has never been demonstrated.…”

“…Preliminary experience suggests that the majority of lenalidomide-exposed patients failing filgrastim mobilization will adequately mobilize CD34 þ cells with filgrastim plus plerixafor. 10,19,20 Moreover, there were no mobilization failures among the few reported lenalidomide-treated patients who underwent upfront mobilization with filgrastim plus plerixafor. 20,21 In this study, we examine 89 patients with MM (49 previously exposed to lenalidomide) who proceeded to steady state growth factor-based AHSC mobilization with preemptive ('just in time') use of plerixafor depending on peripheral blood CD34 þ enumeration on the 4th day of mobilization and following a previously validated and published algorithm.…”

“…[4][5][6] The use of the IMID lenalidomide in the induction regimen was early identified as a risk factor for poor AHSC mobilization. [7][8][9][10] This negative effect, noticed particularly with growth factor mobilization, is at least partially overcome with the use of chemotherapy mobilization, [11][12][13] although this strategy carries higher cost and toxicity. [14][15][16][17] The CXCR4-SDF1-binding inhibitor plerixafor dramatically enhances filgrastim-based CD34 þ mobilization in patients with MM, 18 but is expensive, limiting its use in all patients undergoing mobilization.…”

Identification of prognostic factors for plerixafor‐based hematopoietic stem cell mobilization

“…Overall, the patients were characterized by features that are known to affect standard stem cell mobilization negatively, including advanced age, a diagnosis of NHL, previous radiotherapy, extensive treatment with chemotherapy, treatment with lenalidomide or purine analogues, previous autoSCT, or failure of at least one previous attempt at mobilization [7][8][9][10][11][12][13][14][15]. We observed that, despite these unfavorable characteristics, mobilization with plerixafor and G-CSF enabled the required number of stem cells to be collected in 67.5% of patients.…”

“…A number of factors are known to affect the outcome of stem cell mobilization negatively in the context of traditional mobilization regimens that are based on the administration of G-CSF with or without chemotherapy. These factors include advanced age, a diagnosis of non-Hodgkin's lymphoma (NHL), previous radiotherapy, extensive treatment with chemotherapy, treatment with lenalidomide or purine analogues, and the failure of at least one previous attempt at mobilization [7][8][9][10]. In this study, we decided to investigate whether the above-mentioned factors might allow the prediction of a suboptimal outcome for stem cell mobilization with plerixafor and G-CSF.…”