Autologous Stem-Cell Transplantation for Multiple Myeloma in the Era of Novel Therapies

Ricardo D. Parrondo, MD; Sikander Ailawadhi, MD; Taimur Sher, MD; Asher A. Chanan-Khan, MD; Vivek Roy, MD


J Oncol Pract. 2020;16(2):56-66. 

In This Article

Stem Cell Mobilization and Collection

Apheresis is performed with the goal of collecting at least 2 × 106 CD34+ cells/kg peripheral blood stem cells for a single autologous transplantation. Many centers would collect double this amount if a patient is potentially a candidate for tandem or salvage ASCT in the future. Chemomobilization is useful in patients who need to reduce MM tumor burden and enhance stem cell mobilization. Compared with mobilization with granulocyte colony-stimulating factor (G-CSF) alone, chemomobilization has not yielded superior OS outcomes and has been associated with increased toxicity.[27] Nonetheless, chemomobilization with cyclophosphamide can be considered in the setting of failed stem cell mobilization with G-CSF and/or plerixafor, or in those with progressive disease at the time of stem cell mobilization.[28] Prolonged exposure to lenalidomide therapy has been associated with suboptimal CD34[1] stem cell mobilization.[29] Use of plerixafor and/or chemomobilization with cyclophosphamide and G-CSF has been able to overcome lenalidomide-induced poor stem cell mobilization.[30] It is therefore recommended that stem cell mobilization and collection occur within four to six cycles of lenalidomide-based induction therapy.[30]

Conditioning Regimen

The standard conditioning regimen for patients with MM undergoing ASCT has been melphalan 200 mg/m2. In a phase III RCT, patients who receivedmelphalan 200mg/m2 had superior OS at 45 months (65.8% v 45.5%; P = .05) and less toxicity compared with patients who received melphalan 140 mg/m2 with 8 Gy total body irradiation.[31] Patients with renal dysfunction at the time of ASCT are at risk for higher ASCT-associated morbidity and mortality. As such, patients who have a creatinine clearance less than 60 mL/min who undergo ASCT should receive melphalan 140 mg/m2.[32]

Recently, a phase III RCT that compared busulfan 32 mg/m2 plus melphalan 140 mg/m2 with melphalan 200 mg/m2 conditioning followed by ASCT showed a median PFS of 64.7 months with busulfan plusmelphalan versus 43.5months with melphalan alone (HR, 0.53; CI, 0.30 to 0.91; P = .022).[33] The busulfan plus melphalan group had a higher incidence of grade 2 and 3 mucositis compared with the melphalan group (74% v 14%, respectively). Clinical trials incorporating novel agents into conditioning regimens are underway (Table 2).