(PA-408) Long-term Safety and Efficacy of Autologous Hematopoietic Cell Transplantation for Multiple Myeloma in the Era of Quadruplets

Quadruplets have been introduced as the mainstay of induction treatment in multiple myeloma (MM) patients eligible for autologous hematopoietic cell transplantation (AHCT). We studied the long-term safety and efficacy of AHCT in a large real-world cohort of MM patients receiving quadruplets compared to historic controls induced with triplets.

Methods:   

We enrolled consecutive patients, of our JACIE-accredited center, that received AHCT over the last decade (2013-2023) for MM. Patients were divided into 2 groups: 79 patients were induced with daratumumab-based quadruplets (Group A) versus 187 patients with bortezomib-based triplets (Group B). All patients received high-dose melphalan (200 mg/m2) as conditioning regimen, with dose reduction (140 mg/m2) in 6 patients with chronic kidney disease. Median patient age at transplant date was 59 (41-71) years for group A and 57 (35-70) for group B. Disease status at transplantation was complete response (CR), very good partial response (VGPR), partial response (PR) and progressive disease (PD) in 34/28/11/5 in group A vs 55/64/63/5 in group B. Variables included in the analysis were also CD34+ stem cell yield, time to neutrophil and platelet engraftment and post-transplant outcome regarding overall survival.

Results:   

We studied 266 patients with multiple myeloma, within the above follow-up period. No second AHCT or allogeneic transplantation was performed in the study period. There were no transplant-related deaths.
Within this period, 5-year OS was 83% in Group A patients vs 60% in Group B patients (p=0.003). There was no statistically significant difference in the disease status at transplantation between the two groups. CD34+ stem cell yield was not different in the two groups, 3.91 (1.70-9.48) in group A vs 3.89 (1.38-9.63) x 10^6/kg in group B (p=ns). There was no impact in median time to neutrophil engraftment, 10.6 (in group A (9-13) vs 11.5 (7-26) days in group B (7, (p=ns). However, patients in group A had significantly shorter median time to platelet engraftment, 12.8 (8-26) vs 14.2 (7-68) days (p=0.045).

Conclusions:   

Our data confirm that AHCT is safe and effective for MM in the era of quadruplets. Daratumumab-based quadruplets offer an optimal graft yield and seem to exert an enhanced impact on platelet engraftment, probably due to their alkylator-sparing advantage. The significant benefit in overall survival highlights the importance of incorporating novel agents into the first-line setting, even in transplant-eligible patients, so as to improve total outcomes in this still incurable disease.