Retrospective Analysis of Treatment Outcome Differences with and without Autologous Stem Cell Transplantation in Patients with Dialysis-Dependent Multiple Myeloma (DDMM): KMM2304 Study

Background: Approximately 20-40% of multiple myeloma patients show abnormalities in renal function upon diagnosis, and approximately 2-3% of these patients are dialysis-dependent multiple myeloma (DDMM) patients who require continuous dialysis. Autologous stem cell transplantation performed after remission-inducing chemotherapy can improve the survival of multiple myeloma patients, but little research has been done on the effectiveness and safety of autologous stem cell transplantation in the DDMM patient group.

Patients and methods: The patients receiving dialysis who were newly diagnosed as multiple myeloma from January 2001 to December 2022 in Korea were enrolled in this study. We retrospectively analysed the treatment efficacy and toxicity of autologous stem cell transplantation in newly diagnosed multiple myeloma patients under 70 years of age, which is considered the transplantable age, and a comparison group that did not receive autologous stem cell transplantation under the same conditions.

Results: A total of 130 newly diagnosed DDMM patients were enrolled from twelve Korean institutions. Of the 130 patients, 66 underwent autologous stem cell transplantation after remission-inducing chemotherapy, and 64 underwent remission-inducing chemotherapy alone, with no stem cell transplantation. The median age of both groups was 55 and 62 years, respectively.

There were 47 (71.2%) males in the autologous transplant group and 41 (64.1%) males in the non-transplant group, with no significant difference between the two groups. ECOG PS, Heavy chain type, and R-ISS score were not significantly different between the two groups. High risk cytogenetics were commmon in 1q gain, 17p deletion, and 4;14 translocation in both groups, with no statistical difference between the two groups.

The most common cause of renal dysfunction in both groups was cast nephropathy and light chain deposit disease, with most patients undergoing hemodialysis as renal replacement therapy and only a few undergoing peritoneal dialysis. Remission-inducing chemotherapy regimens in the autologous transplant group were most frequently the VTD-VelDex regimen, while in the non-transplant group it was VMP-VTD regimen. Most patients received reduced doses of melphalan as conditioning chemotherapy. (Table 1)

After remission induction chemotherapy, 15 patients (22.7%) achieved a response of CR, and 19 patients (28.8%) achieved a response of VGPR in autologous transplant group. On the other hand, 11 patients (17.2%) achieved a response of CR, and 14 patients (21.9%) achieved a response of VGPR in non-transplant group. After autologous stem cell transplantation, six patients achived MRD-negativity and fourty patients (60.6%) achieved CR or better response. Even after autologous stem cell transplantation, only one patient (1.8%) responded below PR. The median number of days until discharge after autologous transplantation was 18 days (minimum 10 days, maximum 42 days). (Table 2)

General toxicities such as nausea, vomiting, and diarrhea were mostly grade 1-2, and there was no significant difference in the frequency of occurrence in both groups. The most common side effects were hematological toxicities, the overall frequency of which was significantly higher in the autologous transplant group than in the non-transplant group. Grade 3 or higher hematologic toxicities were also significantly more frequent in the autologous transplant group, while the frequency of febrile neutropenia and grade 3 or higher infectious complications did not differ between the two groups. One patient in the non-transplant group died due to COVID-19 pneumonia.

The progression-free and overall survival rates of involved patients were analyzed using Kaplan-Meier survival analysis. The median progression-free survival rate was 29.8 months (95% CI, 18.8-40.8) in autologous transplant group, and was 9.5 months in non-transplant group. (95% CI, 5.6-13.4) (p < 0.001) The median overall survival rate was 60.4 months (95% CI, 25.0-95.8) in autologous transplant group, and was 40.9 months in non-transplant group. (95% CI, 4.4-77.4) (p = 0.101)

Conclusions: In patients with dialysis-dependent multiple myeloma (DDMM) under the age of 70, autologous stem cell transplantation improves the treatment response rate and survival outcome with tolerable treatment-related toxicities compared with non-transplant patients.

Yoon:Asan Medical Center, University of Ulsan College of Medicine: Current Employment; Abbvie, Abclon, Beigene, BMS, GI cell, GI innovation, GC cell, Verismo, Janssen, Lilly, Novartis, Roche, and Pharos Bio: Consultancy; Abbvie, Beigene, Boryung, Celltrion, Kyowa Kirin, Janssen, Samyang and Sanofi: Honoraria, Research Funding; Regeneron: Membership on an entity's Board of Directors or advisory committees. Lee:Takeda, Janssen, Amgen, Celgene-BMS: Consultancy; Takeda, Amgen, Janssen, Celgene-BMS, Sanofi, Otuka, Pfizer, Celltrion, Boryung, Recordati rare diseases: Honoraria, Speakers Bureau; Amgen, Janssen, JW Pharmaceutical, Otsuka: Research Funding.