Efficacy of Combined Drug Pre-transplant Conditioning Regimens in Multiple Myeloma Patients with Single Autologous Hematopoietic Stem Cell Transplantation

AUTOIMMUNE THROMBOCYTOPENIA

II Kostroma1, AS Zhuk2, ZhYu Sidorova1,3, RR Sabitova1, AYu Aksenova4, OB Belopolskaya4, SS Bessmeltsev1, SV Sidorkevich1, SV Gritsaev1

1 Russian Research Institute of Hematology and Transfusiology, 16 2-ya Sovetskaya ul., Saint Petersburg, Russian Federation, 191024

2 ITMO National Research University, 49 lit. A Kronverkskii pr-t, Saint Petersburg, Russian Federation, 197101

3 BP Konstantinov Petersburg Nuclear Physics Institute of National Research Center “Kurchatov Institute”, 1 Orlova roshcha microdistrict, Gatchina, Leningrad Region, Russian Federation, 188300

4 Saint Petersburg State University, 7/9 Universitetskaya nab., Saint Petersburg, Russian Federation, 199034

For correspondence: Ivan Ivanovich Kostroma, MD, PhD, 16 2-ya Sovetskaya ul., Saint Petersburg, Russian Federation, 191024; e-mail: obex@rambler.ru

For citation: Kostroma II, Zhuk AS, Sidorova ZhYu, et al. Efficacy of Combined Drug Pre-transplant Conditioning Regimens in Multiple Myeloma Patients with Single Autologous Hematopoietic Stem Cell Transplantation. Clinical oncohematology. 2023;16(1):88–95. (In Russ).

DOI: 10.21320/2500-2139-2023-16-1-88-95

ABSTRACT

Aim. To conduct an interim outcome analysis of conditioning regimens with carfilzomib or thiotepa compared to standard melphalan 200 mg/m2 regimen in multiple myeloma (MM) patients with single autologous hematopoietic stem cell transplantation (auto-HSCT).

Materials & Methods. The retrospective analysis focused on outcomes of 67 single auto-HSCTs performed from 2017 to 2021. Responses as well as progression-free (PFS) and overall survival (OS) rates were compared in MM patients per IWMG criteria in pre- and post-transplant periods. Three conditioning regimens were assigned: melphalan 200 mg/m2 (Mel200), melphalan/carfilzomib combination (Mel/Karfil), and melphalan/thiotepa combination (Mel/Thio). In an additional cohort of 12 MM patients, next-generation sequencing assay was used to detect inherited and somatic mutations associated with proteasome inhibitor efficacy. For this purpose, DNA of peripheral blood lymphocytes and bone marrow plasma cells were examined.

Results. PFS medians were comparable in MM patients treated with Mel200 (n = 40) and Mel/Karfil (n = 10) conditioning regimens, they were 32 and 23 months, respectively (p = 0.241). In these cohorts, OS median was not reached, and the curves showed no significant differences (p = 0.050). Out of 10 MM patients treated with Mel/Karfil, six received melphalan 140 mg/m2, the remaining 4 patients received 200 mg/m2. Complete response (CR) rate in the Mel200 and Mel/Karfil groups increased two-fold after auto-HSCT: from 35.5 % to 74.2 % and from 25.0 % to 50.0 %, respectively. The worst PFS and OS medians were in the Mel/Thio group, i.e., 12 and 17 months, respectively, and CR rate after auto-HSCT remained unchanged. The best PFS was associated with CR rather than very good partial or partial response after auto-HSCT, they were 48, 21, and 23 months, respectively (p = 0.001). Exome sequencing of DNA of peripheral blood lymphocytes and bone marrow plasma cells revealed polymorphic variants in the genes associated with chemotherapy response.

Conclusion. The outcomes of Mel/Karfil, the regimen containing the reduced dose of melphalan 140 mg/m2, and the statistical comparability with the Mel200 regimen suggest that this combination can be effective in the treatment of MM patients with impaired renal function, which still needs to be further confirmed. No advantage of the combined conditioning regimen over the standard one can be accounted for by the loss of plasma cell sensitivity to proteasome inhibitors. The obtained data provide ground for modifying the study protocol with a particular focus on evaluating the efficacy and safety of conditioning regimen Mel/Karfil with melphalan 200 mg/m2 depending on biologic phenotype of plasma cell.

Keywords: multiple myeloma, autologous hematopoietic stem cell transplantation, conditioning regimen, melphalan, carfilzomib, thiotepa.

Received: June 15, 2022

Accepted: December 2, 2022

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