Haploidentical Allogeneic Cell Transplantation in Relapsed/Refractory Multiple Myeloma

Purpose: Although emerging therapies for multiple myeloma (MM) have improved treatment options, long-term disease control in relapsed/refractory (r/r) MM remains a challenge. While the effect of natural killer cell alloreactivity in haploidentical allogeneic hematopoietic cell transplantation (HCT) with post-transplantation cyclophosphamide (PTCy) as graft-versus-host disease (GvHD) prophylaxis is considered a standard treatment option for several hematologic neoplasms, its use in MM is controversial. In this retrospective analysis, we evaluated a small cohort of consecutive patients with MM who underwent haploidentical allogeneic HCT with PTCy. Patients and Methods: With a median follow-up of 68 months (range, 2-109 months), seven consecutive patients with r/r MM underwent haploidentical HCT. All were heavily pre-treated, having received proteasome inhibitors, anti-CD38 antibody, immunomodulatory drugs, and at least one autologous HCT. Three patients received a chemotherapy-based reduced-intensity conditioning regimen combined with radioimmunotherapy. GvHD prophylaxis in all patients consisted of PTCy in combination with tacrolimus and mycophenolate mofetil. Results: All patients showed stable engraftment with complete donor chimerism. Haploidentical HCT resulted in initial response in all patients, with four patients achieving a complete remission (CR) and three a very good remission (VGPR) at first disease assessment post- HCT. All individuals surviving beyond day +100 experienced disease relapse or progression. Among the six surviving patients median time to relapse was 26.5 months (range, 5-81 months). At last follow-up, four of five surviving patients maintained a CR, while one patient remained in a very good partial remission, all following subsequent individualized therapies. Acute GvHD grades III-IV were observed in two patients, while four developed mild-to-moderate chronic GvHD, with no GvHD-related deaths at the last follow-up. Conclusion: In this small, selected cohort, haploidentical allogeneic HCT with individualized pre-treatment and conditioning regimens was associated with disease control in heavily pretreated patients with r/r MM.