P50 overall survival advantage of monoclonal antibodies based-treatments in multiple myeloma patients relapsed after allogeneic stem cell transplantation

Even if allogeneic stem cell transplantation (allo-SCT) is curative for a minority of patients with multiple myeloma (MM), the patients who have relapsed after allo-SCT can experience long term survival, suggesting a synergy between anti-myeloma drugs administered after allo-SCT and donor T cells. We evaluated 202 allo-SCTs for MM reported to the Gruppo Italiano Trapianto Midollo Osseo (GITMO) registry between 2009 and 2018: at a median follow-up of 40.9 months after allo-SCT 46 out of 202 patients (23%) died because of non mortality (NRM) causes, 37 patients (18%) were alive without disease progression and 119 (59%) had relapsed. We retrospectively evaluated the outcome of those patients who had relapsed and had received one or more lines of salvage treatment with the aim of collecting data about efficacy of novel drugs after allo-SCT. Median age at transplant was 53 years (range 29-77). Staging according ISS was evaluable for 78 patients and was 1, 2 or 3 in 20 (25%), 24 (31%) and 34 patients (44%) respectively. High risk FISH cytogenetic was present in 35 out of 77 evaluable patients (45%). Allo-SCT was performed after more than 2 lines of treatments in 59 patients (49%). Myeloablative conditioning was administered prior to 72 allo-SCTs (60%). Stem cell source was peripheral blood for 105 allo-SCTs (88%). Cells came from 48 HLA-identical sibling donors (40%), 66 unrelated donors (56%) and 5 haploidentical donors (4%). Relapse occurred at a median of 14.3 months (IQR 7.2-26.9) after allo-SCT, it involved extramedullary sites in 42 patients (35%) and was associated with CRAB symptoms or signs in 59 patients (49%). Thirty-seven patients (31%) were observed without treatment or received chemotherapy or radiotherapy, 9 patients (7%) received at least one salvage treatment including immunomodulating agents, 39 patients (33%) were treated with at least one salvage therapy including proteasome inhibitors, 34 patients (29%) received at least one salvage treatment including monoclonal antibodies (33 daratumumab, 1 elotuzumab). Lines of therapy were □ 1 for 68 patients (57%), 2 for 23 patients (19%), 3 or more for 28 patients (24%). Seventeen patients (14%) died because of NRM causes (2 GVHD, 9 infections, 6 other causes) and 67 patients (56%) died due to MM progression. Two-year and 5-year OS of the whole population were 67.6% (95% IC 58.4-75.3) and 40.8% (95% IC 31.7-49.7) after allo-SCT and 49.3% (95% IC 39.7-58.2) and 26.4% (95% IC 17.9-35.7) after relapse, respectively. OS after relapse was significantly longer after monoclonal antibodies or proteasome inhibitors in comparison with regimens including only immunomodulating agents or chemo-radiotherapy (2-year OS 69.0% vs 57.9% vs 33.3 vs 22.8%, p=0.007)(Fig 1). OS after relapse was longer in patients who had received 3-4 salvage treatment lines in comparison with patients who were treated with □ 2 lines (p=0.064). Donor lymphocyte infusions (DLI) were administered to 27 patients and significantly prolonged OS after relapse (p=0.009). Our study suggested that the administration of monoclonal antibodies-based salvage treatments can enhance the graft-versus-myeloma in patients who experienced relapse after allo-SCT. Moreover, it confirmed that DLI have a significant antimyeloma activity with acceptable severe toxicity.