Allogeneic Stem-Sell Transplantation In Multiple Myeloma In Real Practice: Long-Term Results From a Single Institution
Authors: Jiménez Raquel , Rosiñol Laura , Rovira Montserrat , Fernández-Avilés Francisco , Martínez Carmen , Gutiérrez-García Gonzalo , Suárez-LLedó Maria , De Larrea Carlos Fernández , Urbano Alvaro , Blade Joan 
Published: October 2019

Abstract

Background
Allogeneic stem-cell transplantation with myeloablative conditioning (MAC) in multiple myeloma (MM) is associated with a high transplant-related mortality (TRM) with a 15% of long-term survivors. Allogeneic transplantation with reduced-intensity conditioning (alloRIC) results in a lower TRM with a higher relapse rate. When used in first line in a tandem transplant approach (auto/alloRIC), the incidence of acute graft-versus host disease (aGvHD) grade II-IV reported ranges between 20-43%, chronic GvHD between 50-75% and the TRM between 10-15%. The reported PFS was 25% beyond 7 years. Because of this high morbimortality and the higher rate of relapse, the role of allogeneic transplantation in MM remains controversial, especially as part of the front-lline therapy.

Aim
to analyze the results of allogeneic transplantation in patients with MM outside clinical trials at our institution over a period of 27 years.

Patients and Methods
Between Feb 1986 and April 2009, 23 patients (17 M, 6 F, median age 41 –range 21-52 -) received a MAC from an HLA identical sibling donor. Disease status at the time of transplant was first response in 12 patients (53%) (3 CR, 9 PR), sensitive relapse in 3 (13%) (all PR) and refractory disease in 8 (35%). Conditioning regimen was heterogeneous (6 Cyclo/TBI, 2 Bu/Cyclo, 3 BCNU/Mel/Cyclo/TBI, 4 Cyclo/Mel/TBI, 5 Mel/TBI, 2 Bu/Mel). GvHD prophylaxis consisted on cyclosporine/MTX (10), cyclosporine/PDN (8), cyclosporine (2) or other (3).
Between April 2001 and Aug 2012, 31 patients (18 M, 13F, median age 48 –range 25-64) received an alloRIC: 25 of them (80%) from an identical sibling donor and 6 (20%) from an unrelated donor. Seven patients (13%) who did not achieve a CR after front-line autologous transplant received an alloRIC in a tandem strategy. 17 (31%) were in sensitive relapse (first relapse 14, second relapse 3). Seven patients (13%) had refractory disease at the time of alloRIC. Conditioning regimen consisted on Fluda/Mel (26 patients), Flu/TBI (3) and Fluda/Mel/bortezomib (2). GVHD prophylaxis consisted on cyclosporine/MTX (6) or cyclosporine/MMF (25). All patients in the alloRIC group had received a prior single autologous transplant.

Results
On an intention-to-treat analysis, the CR rate after MAC was 35%. The incidence of aGvHD grade II-IV and III-IV were 48% and 39%, respectively. The TRM at any time was 56%. The causes of death were GvHD in 7 patients, infection not related to GvHD in 5 patients and VOD in 1 patient. The relapse rate was 30%.There are 3 patients who remain in continued CR at 13, 23 and 27 years beyond transplantation.
With alloRIC the CR rate was 45%. The incidence of aGvHD grade II-IV and III-IV were 55% and 22%, respectively. Nine patients develop chronic GvHD. The TRM at any time was 29% and the causes of death were GVHD in 7 patients and pulmonary hemorrhage and postransplant lymphoma one patient each. Nine patients remain alive in continued CR from 5 months to 9 years of follow-up.
After a median follow-up of 36.4 months, the median PFS was not significantly different between MAC and alloRIC and there was a trend towards a longer overall survival in the alloRIC group (4.6 vs 35 months, p=0.05).

Conclusions
Although a small fraction of patients with MM can be cured with MAC allogeneic transplantation, this procedure is associated with an extremely high TRM. Unfortunately, alloRIC was also associated with a high incidence of severe aGVHD resulting in a high TRM leading to a short PFS. New approaches aimed at decreasing the incidence of aGVHD are crucial.

Disclosures:
Jiménez: Janssen: Honoraria. Rosiñol:Janssen: Honoraria; Celgene: Honoraria. Blade:Janssen: Honoraria; Celgene: Honoraria.