[Efficacy and safety of oral melphalan as conditioning regimen for autologous hematopoietic stem cell transplantation in multiple myeloma].

Abstract

Objective: To investigate the safety and efficacy of oral melphalan as a conditioning regimen for patients with multiple myeloma (MM) who underwent autologous hematopoietic stem cell transplantation (auto-HSCT) . Methods: This retrospective cohort study collected clinical data of patients with MM who underwent auto-HSCT at Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from July 2022 to October 2023. Patients were divided into oral and intravenous groups according to the administration route of melphalan. Engraftment time (ET), overall responses, long-term outcomes, and melphalan-associated toxicities were assessed. The pharmacokinetics of melphalan were detected using a mass spectrometer. Results: This study included 48 patients with MM who met the inclusion and exclusion criteria. Of these patients, 12 received tablet melphalan and 36 had the injection formulation. Upon engraft infusion, time to the lowest level (TTLL) and ET of neutrophils in the oral group were significantly longer than those in the injection group[TTLL: median, 9.0 (7.0-13.0) d vs 7.0 (5.0-12.0) d, P<0.001; ET: median, 12.0 (10.0-14.0) d vs 11.0 (9.0-12.0) d, P<0.001]. Such a lag also happened to the TTLL and ET of platelets in the oral group compared with the injection group[TTLL: median 10.0 (9.0-15.0) d vs 9.0 (6.0-13.0) d, P=0.004; ET: median, 14.5 (11.0-17.0) d vs 12.0 (9.0-19.0) d, P=0.002]. The lowest level of neutrophils in the oral group was higher than that in the injection group (0.11×10(9)/L vs 0.02×10(9)/L, P<0.001), whereas the lowest level of platelets in both groups had no statistical difference (P>0.05). The median duration of neutropenia (<0.5×10(9)/L) was comparable between the two groups. Regarding non-hematological side effects, patients who took melphalan orally had a remarkably lower frequency of gastrointestinal toxicities as opposed to those given intravenously (nausea: 50.0% vs 100.0%, P<0.001; vomiting: 8.3% vs 69.5%, P=0.001; diarrhea: 50.0% vs 83.3%, P=0.030). The incidence of oral mucositis and liver or kidney impairments did not differ between the two groups. Post-auto-HSCT efficacy evaluation demonstrated no differences in the percentages of patients obtaining a very good partial response and better outcomes, as well as in the improvement rate to complete remission. With a median follow-up time of 37.9 (31.0 - 49.4) months, the median progression-free survival (PFS) of the oral and injection groups was not reached and 35.9 months (95% CI: 28.3 months-not reached), respectively. Median overall survival (OS) was not reached for either. Neither PFS nor OS reached statistical significance between the two groups. To examine the drug bioavailability, melphalan pharmacokinetics were tested in 6 patients, comprising 3 from the oral group and 3 from the injection group. The result demonstrated that both formulations reached their peak levels in 30 min. Although the oral melphalan exposure on average was 82.2% of the injection dosage form, there was no significant difference in bioavailability. Conclusions: Oral melphalan, as a conditioning regimen for auto-HSCT in paients with MM, demonstrated favorable bioavailability, a low incidence of adverse reactions, and good clinical efficacy.