Impact of Prior Lenalidomide Treatment on Peripheral Blood Stem Cell (PBSC) Mobilization in Untreated Multiple Myeloma (MM) Patients.

Background: Immunomodulatory drugs (e.g. thalidomide and lenalidomide) are increasingly being used for induction therapy prior to stem cell harvest in MM. We have previously reported that induction therapy with a thalidomide-based regimen leads to a lower yield of stem cells when compared to bortezomib. This resulted in a reduced yield of stem cells per collection and an increased number of phereses required to reach our target goal. Delay in engraftment of platelets by a median of 1 day was also observed. We now report lower PBSC yields in patients receiving lenalidomide induction therapy.

Methods: Data was pooled from 2 centers on patients who received lenalidomide induction therapy followed by PBSC mobilization. Twenty of 28 patients received G-CSF 10 micrograms/kg for four days; 8 patients were mobilized with 7.5 mcg/kg G-CSF plus 7.5 mcg/kg GM-CSF for 5 days.

Results: Eight of 28 patients (40%) failed to collect sufficient cells for even 1 transplant (less than 2 x 10⁶ CD34+ cells/kg. Of note, 2 of these patients also failed to mobilize sufficient stem cells when treated with the CxCR4 inhibitor AMD3100 plus G-CSF on a compassionate use protocol. These patients subsequently had successful mobilization following cyclophosphamide chemotherapy mobilization. Our data mirrored those of Kumar et al (Leukemia 2007 Jun 21; [Epub]) in several aspects. After lenalidomide therapy, there was a decrease in total number of CD34+ cells/kg in day 1 collections and total number of days required to collect sufficient CD34+ cells when compared to chemotherapy or bortezomib induction therapy. However, our data differed from those of Kumar et al regarding the correlation of number of cycles of lenalidomide therapy and subsequent PBSC collection. Kumar et al reported no failures in patients who had less than 6 cycles of lenalidomide. In contrast, 5 of our failures had received only 4 or 5 cycles of lenalidomide.

Conclusions: Patients treated with lenalidomide induction therapy have lower stem cell yields with growth factor mobilization. Biologically, the action of Imids may be different from those of bortezomib on the bone marrow stroma. These lower yields may become clinically important when attempting to obtain stem cells from elderly patients, those with prior radiation therapy or with higher bone marrow plasma cell infiltration. Our group has elected to use cyclophosphamide for mobilization of patients treated with prior lenalidomide and we have been successful in 4/4 patients so far.