Predictors of autologous hematopoietic stem cell transplantation efficacy in patients with multiple myeloma

Background. Multiple myeloma (MM) remains a chronic hematologic malignancy. However, treatment outcomes have improved significantly due to the introduction of new targeted agents and high-dose therapy with autologous hematopoietic stem cell transplantation (auto-HSCT) into clinical practice. Several researchers have demonstrated that the efficacy of high-dose chemotherapy with auto-HSCT is superior to the use of low-intensity antitumor therapy alone, even in the era of targeted agents. Despite this, disease relapses after auto-HSCT remains a major problem limiting the potential for a biological cure for MM. It is important to identify significant prognostic factors whose correction could help prevent adverse outcomes in MM treatment.

Aim. To determine the efficacy of auto-HSCT and to study progression-free survival (PFS) rates of MM patients depending on various clinical and laboratory parameters.

Materials and methods. The single-center study included 803 patients with MM aged from 19 to 69 years (median 54 years), who underwent high-dose chemotherapy followed by single or tandem auto-HSCT from June 2000 to January 2025. The diagnosis was established in accordance with the criteria adopted by the International Myeloma Working Group (IMWG) with successively revised parameters and updated in 2014. Before the collection of hematopoietic stem cells all patients received induction therapy, including chemotherapeutic agents only (VAD, EDAP) in 38 cases, bortezomib in 765 cases, lenalidomide in 217 patients, and daratumumab in 51 cases. Single high-dose chemotherapy (melphalan 140–200 mg / m²) followed by auto-HSCT was administered to 515 patients, and tandem chemotherapy was administered to 288 patients. The antitumor response was assessed (revised for the retrospective group) for all patients according to the IMWG-2016 criteria after induction therapy, before auto-HSCT, and on day 100 thereafter. The study results were statistically analyzed using MedCalc.

Results. Immunoglobulin G secretion was detected in 53 % of MM patients at disease onset, plasmacytomas were detected in 39 % of cases, and Durie–Salmon stage IIIA was diagnosed in 71 % of patients. After auto-HSCT, the rate of achieving stringent complete remission was 29 %, complete remission – 26 %, very good partial remission – 31 %, partial remission – 8 %, stabilization of disease – 2 %, and progression / relapse was recorded in 4 % of patients. A total of 320 (40 %) patients with MM showed an improvement in the antitumor response on the day 100 after the first auto-HSCT compared with the results of induction treatment. After completion of the high-dose phase, including one or two auto-HSCT, maintenance therapy was prescribed in 58 % of cases and in 42 % of cases, patients were monitored until progression without post-transplant treatment. The median PFS of patients was 36 months, while the probability of 5-year PFS was 32 %, and 10-year PFS – 20 %. The median PFS in the group of patients with standard cytogenetic risk was significantly higher and amounted to 40 months (95 % confidence interval 32–43) versus 26 months (95 % confidence interval 14–37) in the high-risk group (p < 0.05).

Based on the results of survival parameters assessment depending on the antitumor response achieved after auto-HSCT the median PFS was 104 months in case of stringent complete remission, 29 months for complete remission, 30 months for very good partial remission, 19 months for partial remission, 5 months for disease stabilization, and 4 months for progression / relapse on the day 100 after auto-HSCT (p < 0.001). Multivariate Cox regression analysis showed that the probability of disease relapse / progression after autologous stem cell transplantation was statistically significantly associated with three factors: stage III (International Staging System), failure to achieve a stringent complete remission after auto-HSCT, and the absence of maintenance therapy (p < 0.05).

Conclusion. A long-term follow-up period allows confirming the high significance of auto-HSCT in the treatment algorithm for MM patients, as the probability of maintaining remission achieved after transplantation for 10 years was 20 %.