Haploidentical Allogeneic Cell Transplantation in Relapsed/Refractory Multiple Myeloma

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.

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.

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.

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.