Low Dose TBI Based Nonmyeloablative Conditionings for Allografting in Multiple Myeloma: Impact of Disease Status at Transplant.
Authors: Giaccone Luisa , Rotta Marcello , Allione Bernardino , Carnevale-Schianca Fabrizio , Rosanelli Carlo , Ciccone Giovannino , Casini Marco , Capaldi Antonio , Aitoro Gabriele , Omedè Paola , Battaglio Silvano , Massaia Massimo , Coser Paolo , Aglietta Massimo , Levis Alessandro , Storb Rainer , Bruno Benedetto , Boccadoro Mario 
Published: April 2020

Abstract
The curative potential of allogeneic hematopoietic cell transplantation (HCT) with low dose total body irradiation (TBI) based conditionings relies exclusively upon a graft-versus-myeloma effect through donor lymphocytes. Thus, low tumor burden and well-controlled disease at transplant could play a pivotal role. Forty-four consecutive patients with myeloma were treated at 4 different Institutions. Thirty newly diagnosed patients (group A) received a planned autologous transplant with melphalan 200 mg/m2 followed by 200 cGy TBI and allogeneic G-CSF mobilized PBSC infusions from HLA identical siblings. Median time from diagnosis to HCT was 9 months (range, 5–46). At allografting, 7 (23%) patients were in complete remission (CR), 17 (57%) in partial response (PR) and 6 (20%) had refractory disease. The remaining 14 patients received fludarabine 90 mg/m2 and 200 cGy TBI followed by allogeneic PBSC from HLA identical siblings as salvage therapy (group B) after a median of at least 2 lines of previous chemotherapy (range, 2–5); all patients, except one, had received 2 autologous transplants. Patients in group B underwent allografting at a median of 37 months (range, 15–105) from diagnosis; 7 (50%) were in PR, 3 (21%) had refractory disease and 4 (28%) were in overt progression. Post-grafting immunosuppression consisted of cyclosporine and micophenolate mofetil in both groups. All patients readely engrafted with median donor T cell chimerism of 97% (range, 55–100%) at day 100. Overall, 64% (28/44) and 43% (19/44) patients developed acute graft-versus-host disease (GVHD) and chronic clinical extensive GVHD, respectively. There were no significant differences in engraftment kinetics and incidence of GVHD between the 2 groups. After a median follow-up of 16 months (range, 2–50) in group A and 19 months (range, 2–48) in group B, treatment related mortality was 23% among patients who received HCT earlier (group A) and 21% among those who were treated later (group B) in the disease course. Overall survival was 74% and 43% in group A and B, respectively. Disease responses are described in the table.
n complete remission partial response stable disease progression Disease response Group A 30 17 6 7 0 Group B 14 0 0 3 11 p value – 0.0001 0.08 0.3 &lt;0.0001
Among patients in group A, 4 relapsed after obtaining CR. Three of them received donor lymphocyte infusion (DLI): 1 achieved CR, 1 PR and 1 had stable disease. Of the 14 patients in group B, 5 received DLI because of relapse/disease progression: 2 obtained PR, and 3 progressed. In conclusion, these findings indicate that graft-versus-myeloma effect appears more effective if HCT is performed earlier after diagnosis in patients with low tumor burden.