Unmanipulated Haploidentical Allogeneic Hematopoietic Cell Transplantation for Multiple Myeloma Using Post Transplant Cyclophosphamide Anti-Gvhd Prophylaxis
Authors: Castagna Luca , Mussetti Alberto , Devillier Raynier , Dominietto Alida , Marcatti Magda , Milone Giuseppe , Maura Francesco , Bruno Benedetto , Furst Sabine , Blaise Didier , Corradini Paolo , Montefusco Vittorio 
Published: October 2019

Abstract
Backgrounds: Allogeneic Hematopoietic Cell Transplantation (HCT) is a potentially curative treatment for fit patients with relapsed/refractory multiple myeloma (MM). When a HLA-identical donor is not available, haploidentical HCT (haploHCT) represents an acceptable therapeutic option, especially when post-transplant cyclophosphamide (PT-Cy) is used as anti-GVHD prophylaxis.
Patients and methods: Twenty-nine patients (median age 56 years, range 47-70) undergoing myeloablative (n=15) or reduced-intensity (n=14) haploHCT from February 2011 to November 2015 are included in this retrospective analysis. The median number of previous lines of therapy was 2 (range 1-7) with 27 (93%) of patients having previously performed an autologous HCT. Both bortezomib and lenalidomide were used in 27 (92%) patients before haploHCT. Eighteen patients (62%) had chemosensitive disease at time of haploHCT (CR=4, VGPR=9, PR=5) and 11 (38%) had chemorefractory disease (PD=7, SD=4). Graft source was marrow-derived in 59% (n=17) and peripheral blood in 41% (n=12) of patients. Standard post-transplant cyclophosphamide anti-GVHD prophylaxis (50mg/mq day +3 and +4 or +5) plus mycophenolate and cyclosporine (n=24) or tacrolimus (n=3) or rapamycine (n=2) was used for the whole study cohort. Overall survival (OS) and Progression Free Survival (PFS) were performed with Kaplan-Meier analysis. Neutrophil and platelets engraftment, acute GVHD, chronic GVHD, Non-Relapse-Mortality (NRM) and Relapse Incidence/Progression of Disease (RI/POD) were obtained with competing risk analysis.
Results: At day +30, neutrophil and platelets engraftments were 86% (95%CI:65-95) and 59% (95%CI:38-74), respectively. Acute GVHD grade >2 at days +100 and +180 were 38% (95%CI: 20-55%) and 41% (95%CI: 23-59%), respectively. All grade chronic GVHD at 12 and 18 months was 21% (95%CI: 8-37. At 18 months, RI/POD was 39% (95%CI:20-58%) and NRM 15% (CI95%:5-32). With a median follow-up in survivors of 16 months (range 5-55 months), the 18-month OS and PFS were 68% (95%CI: 47-82%) and 34% (95%CI: 15-54%), respectively. Chemorefractory disease at transplant was associated with a worse 18-month RI/POD (70% vs 18%, p=<0.01) and a markedly reduced PFS (9% vs 57%, p=0.04) and OS (53% vs 78%, p=<0.01) (Figure 1). Survival outcomes were similar between marrow-derived and peripheral blood graft source cohorts.
Conclusions: HaploHCT is a feasible and effective strategy in patients with relapsed/refractory high-risk multiple myeloma. Chemorefractory disease at transplant was the only prognostic factor associated with a significant reduced RI/POD, PFS and OS.
Figure Kaplan-Meier estimates of progression free survival from time of transplant of the chemosensitive and chemorefractory disease. Figure. Kaplan-Meier estimates of progression free survival from time of transplant of the chemosensitive and chemorefractory disease.

Disclosures
No relevant conflicts of interest to declare.