Challenges in Stem Cell Harvesting for Multiple Myeloma Patients Undergoing Induction with Quadruple Therapy
Authors: Tanase Alina Daniela , Lipan Lavinia Eugenia , Stroe Alexandra , Rotaru Ionela , Colita Anca 
Published: December 2024

Introduction: Although quadruple therapy in the induction of treatment for Multiple Myeloma has become standard, autologous stem cell transplant (ASCT) remains indicated in eligible patients (Rajkumar SV et al. Multiple myeloma: 2022 update on diagnosis, risk stratification, and management. Am J Hematol. 2022). However, 6-27% of patients with Multiple Myeloma will fail to harvest the desired amount of CD34+ stem cells, thus will require a second mobilization strategy, increasing the costs and time the patient is hospitalized (Hsu TL et all, Risk Factors and Outcomes of Stem Cell Mobilization Failure in Multiple Myeloma Patients. Transfus Med Hemother. 2022 Sep). With poor mobilizers, some essential traits that need to be considered are age, prior radiotherapy, use of immunomodulatory drugs, and monoclonal CD38 antibodies (He X et all., Predictive factors for peripheral blood stem cell mobilization in multiple myeloma in the era of novel therapies: A single-center experience. Cancer Med. 2024).

Therefore, we conducted a retrospective analysis to evaluate the mobilization outcome in patients diagnosed with Multiple Myeloma and to determine how the various treatment options influenced the amount of CD34+ stem cells collected.

Methods: We conducted a retrospective study of 154 patients who performed peripheral stem cell (PBSC) harvest at the Bone Marrow Transplant at Fundeni Clinical Institute, Bucharest, Romania, between January 2020 and June 2024. Harvest was conducted using 10-15 µg/kg/day, sub-cutaneous G-CSF for 4-5 days. Poor mobilizers were considered patients who were not able to harvest a PBCS of at least 2 x10^6 CD34/kgc after G-CSF. Poor mobilizers were readmitted to hospitalization after at least 4 weeks, and Plerixafor or Cyclophosphamide (CFS) was used.

Results: Of the 154 patients, 47 (31%) failed to mobilize with G-CSF-alone. Patients at risk for poor mobilizer were considered those who received prior treatment with Radiotherapy (15/154), treatment with Daratumumab (59/154), immunomodulator (94/154), respectively, double therapy with both immunomodulator and anti-CD38 (15/154). Also, the presence of extramedullary disease at diagnosis, the number of induction cycles used, patient age, and disease status before harvest were analyzed. The risk of harvest failure was 41% (24/59) among patients receiving anti-CD38 (p=0.031), 21% (20/94) in those with an immunomodulator therapy (p= 0.161), and 67% (10/15) for those with both of them (p=0.001); but immunomodulator treatment was stopped within 14 days before harvest. Plerixafor was used in 30/47 cases and CFS in 17/47 patients. Graft quality analyses showed that Plerixafor comes with a better graft - mean 6.3±2.7 (2.4-13) versus CFS - mean 4.9 ±2.5 (2.0-12.6) but without statistically significant differences (p=0.773).

Conclusion: In the era of quadruple therapy, the increased rate of poor mobilizers makes harvesting challenging. Scientific research acknowledged that immunomodulators and anti-CD38 agents both raise the risk; however, using both in the same treatment regimen introduces an additional risk. Early recognition of patients at risk indicate using Plerixafor or CFS from the first admission, with reducing hospitalization costs and readmissions for a new harvest. Further studies are needed to determine the best moment for harvest in patients with MM who receive quadruple therapy, and which, Plerixafor or CFS, is preferable and at what time.