Allogeneic Hematopoietic Stem-Cell Transplantation with Reduced-Intensity Conditioning in Patients with Refractory and Relapsing Multiple Myeloma: Long-Term Follow-up.
Authors: Shimoni Avichai , Hardan Izhar , Ayuk Francis , Schilling Georgia , Atanackovic Djordje , Zeller Wolfgang , Shem-Tov Noga , Rand Avital , Yerushalmi Ronit , Zander Axel , Kroger Nicolaus , Nagler Arnon 
Published: October 2019

Abstract
Abstract 3359
Poster Board III-247
Allogeneic stem cell transplantation (SCT) with myeloablative conditioning is potentially curative therapy for multiple myeloma, but is associated with excessively high rates of non-relapse mortality (NRM). Reduced-intensity conditioning (RIC) allows reduction of NRM compared with myeloablative conditioning but relapse rate is increased. The role and timing of allogeneic SCT during the disease course are still controversial. There is also only limited data on the long-term outcome of RIC in the relapsing/ refractory setting. We retrospective analyzed SCT outcomes in 50 patients, given RIC for relapsing/ refractory myeloma between the years 2000-2004. The median age was 53 years (range, 32-64), 29 male, 21 female. This was a relatively heavily pretreated patient group, a median of 3 years from diagnosis (0.5-14 years). Forty-seven patients failed one (n=31) or two (n=16) prior autologous transplants, while 3 patients did not have an autologous transplant due to a failed stem-cell collection, but failed other therapies. The median time from the last autologous SCT was 2 years (range, 3 months to 6.5 years). Thirty patients were in partial (PR, n=26) or complete remission (CR, n=4) at the time of SCT and 20 patients had stable or progressive disease (PD). Patients given an auto/allo tandem transplant (rarely performed outside prospective clinical studies) were not included in this analysis. All patients were given fludarabine-melphalan (100-140 mg/m2) based conditioning and stem-cell grafts from a related (n=27) or unrelated donor (n=23). Disease response was assessed at day +100. Forty patients were evaluable for assessment; seven have died by day +100 of non-relapse causes and three have already relapsed. Twenty-three patients achieved a CR (4 in CR pretransplant, 15 of 26 in PR pretransplant; 4 of 20 in stable/PD) and 17 patients achieved a partial response. Twenty-four patients had disease progression after SCT with a cumulative incidence of 48% (95% CI, 36-64). There were no late relapses beyond three years from SCT. The cumulative incidence of acute GVHD grade II-IV and grade III-IV were 51% (95 C.I. 39-67%) and 19% (95 C.I. 10-37%), respectively. Chronic GVHD occurred in 20 of 40 evaluable patients with an overall cumulative incidence of 63% (95 C.I. 47-84%). With a median follow-up of 6.4 years (range, 5-7.9 years), 16 patients are alive and 34 have died. Thirteen patients died of treatment-related complications [cumulative incidence 26% (95 C.I. 17-42%)] and 21 of disease relapse. Three additional patients relapsed, but are currently alive with further therapies. In all, the median survival is 2.3 years and the estimated 7-year overall and progression-free survival (PFS) rates were 34% (95 C.I. 21-47%) and 26% (95 C.I. 14-38%), respectively. The PFS curve showed an apparent plateau after 3 years, suggesting a potential cure. In a multivariate analysis, adverse prognostic factors for survival included SCT not in remission, long duration of disease (> 5 years from diagnosis) and transplantation from a female donor to a male recipient. Related and unrelated donor transplants had a similar outcome. The 7 year PFS in 19 patients with none of these adverse prognostic factors was 47%. Chronic GVHD and achievement of complete remission after SCT were associated with improved outcome. In conclusion, allogeneic SCT can result in long-term progression-free survival in a subset of myeloma patients failing prior therapy and should be considered early after failure and preferably after achieving a response with salvage therapy. The treatment goal is to achieve a CR as this is associated with better outcome. Relapsing disease is still the major cause of treatment failure. Additional strategies, such as maintenance therapy with novel agents or judicious use of donor lymphocyte infusions merit further investigation for converting PR to CR and for reducing post-transplant relapse risk.

Disclosures:
No relevant conflicts of interest to declare.