Busulfan and cyclophosphamide as a conditioning regimen for autologous transplantation in patients with multiple myeloma after treatment with proteasome inhibitors and/or immunomodulatory drugs

초록

Introduction Due to the coronavirus disease 2019 pandemic, there have been issues of inadequate melphalan (MEL) supply in some regions of the world including the Republic of Korea. In this situation, busulfan (BU) and cyclophosphamide (CY) may be considered as an alternative conditioning regimen for autologous transplantation in patients with multiple myeloma (MM). However, most studies on the effi cacy of the BU/CY regimen were conducted before the introduction of proteasome inhibitors (PIs) or immunomodulatory drugs (IMIDs) for the MM treatment. Therefore, this study evaluated the effi cacy of the BU/CY regimen compared with that of the MEL regimen in patients with MM after treatment with PIs and/or IMIDs. Methods We retrospectively analyzed patients with MM from July 2009 to July 2022. Patients who met the following criteria were included: (1) patients who had undergone autologous transplantation, (2) patients treated with PIs and/or IMIDs before transplantation, and (3) patients who received conditioning chemotherapy with the MEL or BU/CY regimen. MEL regimen comprised of intravenous MEL administration at a dose of 100 mg/m2 on days -3 and -2. BU/CY therapy consisted of intravenous CY at a dose of 60 mg/kg on days -6 and -5, followed by intravenous BU at a dose of 3.2 mg/kg from day -4 to -2. Results: A total of 137 patients were analyzed (MEL: 113 patients and BU/CY: 24 patients). The proportion of patients treated with PIs and/or IMIDs was higher in the BU/CY group than in the MEL group (MEL: 59.3%, and BU/CY: 87.5%, p= 0.027). Additionally, very good partial response (VGPR) or complete remission (CR) at transplant and the proportion of post-transplant maintenance therapy was higher in the BU/CY group than in the MEL group (MEL: 58.4%, and BU/CY: 91.7%, p= 0.034, and MEL: 15.9%, and BU/CY: 62.5%, respectively, p< 0.001). There were no differences in other baseline characteristics such as age, gender, subtype, performance score, International Staging System (ISS) stage, presence of high-risk chromosomal abnormalities, and the time from diagnosis to autologous transplantation. Median progression-free survival from the time of transplantation (PFS) was 29.7 months and 46.8 months in the MEL and BU/CY groups, respectively (p= 0.018). Multivariate analysis for PFS showed that the BU/CY regimen (hazard ratio (HR): 0.313, 95% CI: 0.128–0.765, p= 0.011), ISS stage I (HR: 0.4523, 95% CI: 0.253–0.806, p= 0.007) and VGPR or CR at transplant (HR: 0.108, 95% CI: 0.230–0.501, p= 0.004) were significantly associated with good prognosis. No treatment-related mortality was noted in either group by day 100. Conclusions In patients treated with PI and/or IMID before autologous transplantation, BU/CY may represent an alternative conditioning regimen to the MEL regimen.