Reviewing the Eras: A Retrospective, Single-Centre Review of Peripheral Blood Stem Cell Mobilisation Following Bortezomib, Lenalidomide and Dexamethasone Induction in Comparison to Bortezomib, Cyclophosphamide and Dexamethasone for Multiple Myeloma

In Australia, a triplet induction regimen with bortezomib, lenalidomide and dexamethasone (VRd) for newly diagnosed transplant eligible multiple myeloma (ND-TE-MM) patients has been standard of care since 2020, replacing bortezomib, cyclophosphamide and dexamethasone (VCd). Post induction, eligible patients proceed with an autologous stem cell transplant (ASCT). Lenalidomide exposure is associated with higher rates of mobilization failure, lower CD34+ cell yield and increased apheresis sessions for stem cell collection, when mobilized with granulocyte colony-stimulating factor (G-CSF) alone (Kumar et al, 2007). Our institution utilises a cyclophosphamide (2g/m² intravenously) and G-CSF peripheral blood stem cell (PBSC) mobilisation regimen. We assessed PBSC mobilisation in patients receiving VRd compared to a historical cohort who received VCd induction, specifically assessing their stem cell mobilisation yield, apheresis attempts and engraftment outcomes.

We performed a retrospective review of ND-TE-MM patients at The Princess Alexandra Hospital, Brisbane who received an autologous transplant between January 2018 and December 2023. The patients were categorised into cohorts based on their induction regimen: VCd (cohort 1), three cycles of VRd (cohort 2) and four (or more) cycles of VRd (cohort 3). All patients were followed by PBSC mobilisation. The Stem Cell Laboratory database and the patients' electronic medical records were used to gather demographic data, disease response pre PBSC mobilisation, Plerixafor use, number of apheresis sessions, total CD34+ yield (10⁶/kg) and days till neutrophil (> 0.5x10⁹/L) and platelet (> 20x10⁹/L) count recovery. Successful collection was defined as yielding enough CD34+ cells to meet the minimum criteria of CD34+ cells (2x 10⁶/kg) based on ideal body weight (IBW). The Mann-Whitney test using Graph Pad Prism was used for analysis, with P value of <0.05 considered significant.

There were 77 ND-TE-MM patients identified and 58% were male. Cohort 1 had 30 patients, cohort 2 had 29 patients and cohort 3 had 18 patients. The mean patient age was 57 years. More patients receiving VRd induction (cohort 2 and 3) had achieved a very good partial response (VGPR) or higher (59% and 72%) prior to ASCT, compared to patients receiving VCD induction (cohort 1, 50%). The mean number of days required for apheresis was 1.9, 2.0 and 2.3 for cohort 1,2 and 3 respectively. No collection in any cohort failed to meet the minimum criteria for transplant (CD34+ <2 x 10^6/kg IBW). The mean total CD34+ count (10⁶/kg; 95% confidence interval) was 10.03 (8.26-11.81) for cohort 1, 9.15 (7.39 - 10.91) for cohort 2 and 11.62 (8.95 - 14.29) for cohort 3. The median CD34+ count (10⁶/kg) was 9.28, 8.28 and 11.36 for cohort 1,2 and 3. There was no significant difference in the total CD34+ count between the VCd and VRd patients (P = 0.3637 cohort 1 vs cohort 2; P = 0.2293 cohort 1 vs cohort 3), nor between patients who received three versus four VRd induction cycles (P = 0.0609). A significant difference was observed between the number of patients who had VCd induction and required Plerixafor support for PBSC mobilisation versus those who had three cycles of VRd (7% vs 22%; P < 0.05). Treatment with three versus four cycles of VRd did not significantly affect Plerixafor use (P=0.1681). The median number of days for neutrophil count recovery was 11, 11 and 10 days for cohorts 1, 2 and 3 respectively. There was a significant difference (P <0.05) in the number of days taken to achieve neutrophil recovery between patients who received VCd compared to four cycles of VRd induction. Treatment with three cycles of VRd did not significantly affect neutrophil recovery compared with VCd (P=0.1007). The median number of days for platelet recovery was 17, 18 and 16 for cohort 1,2 and 3 respectively. No significant difference was observed in the number of days needed for platelet recovery between patients who received VCd compared to VRd (P = 0.1093 cohort 1 vs cohort 2; P = 0.6505 cohort 1 vs cohort 3) or between the two VRd groups (P = 0.1042).

Our centre's upfront use of a cyclophosphamide and G-CSF based mobilisation strategy is effective in ensuring that patients post three or four cycles of VRd induction therapy can yield enough stem cells for the intended number of ASCTs. A change to a lenalidomide based induction resulted in an increased use of plerixafor rescue, but was no significant difference in stem cell yield or engraftment.

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