Follow‐up of patients with progressive multiple myeloma undergoing allografts after reduced‐intensity conditioning

Abstract

Summary. Allogeneic stem cell transplantation (allo‐SCT) after reduced‐intensity conditioning was evaluated in 22 patients (median age 53, range 36–66 years) with multiple myeloma with progression after an autologous SCT. Seven patients received a transplant from a human leucocyte antigen (HLA)‐identical sibling and 15 patients (68%) from an unrelated donor [including 3/22 (14%) from a HLA‐mismatched unrelated donor]. Graft‐versus‐host disease (GVHD) prophylaxis consisted of serotherapy with antithymocyte globulin (ATG) and cyclosporine (CSA) (n = 12) or CSA plus mycophenolate mofetil (n = 10). Despite of heavy pretreatment, the transplant‐related mortality (TRM) for all grafted patients was acceptable at 5/22 patients (23%). Seven of 21 patients (33%) that were evaluated developed grade II GVHD and one (5%) patient developed grade III/IV acute GVHD. Seven patients developed chronic GVHD (cGVHD), but only one was extensive. Eleven patients died of progressive disease within a median of 7 months (2–19 months) post transplant. Thirteen of all 22 patients (59%) achieved a partial or complete remission with six of these 13 patients (46%) remaining event free at a median of 24 months (range 8–36 months) post allografting. Estimated 2 year overall and event‐free survival was, respectively, 25·5% and 22·0% for the whole patient group, and 62·5% and 57·1% for patients with chemosensitive disease. Chemorefractory disease prior to allogeneic stem cell transplantation (P = 0·0182) and absence of cGVHD (P = 0·069) were associated with shorter event‐free survival. Thus long‐term disease control can be achieved, but is restricted to patients responding to prior salvage chemotherapy.

Toxicity-reduced, myeloablative allograft followed by lenalidomide maintenance as salvage therapy for refractory/relapsed myeloma patients

“…Even if the true value of lenalidomide post allograft can only be determined by a prospective randomised study, the relative long PFS of 52% at 3 years is higher than the reported 3-year PFS in similar allogeneic studies without lenalidomide. 2,3,8,9 In the current trial, neither del 13q14 or the use of mismatch donors could be identified as risk factor for survival. As data about t(4;14) or 17p were not available in all patients, a detailed cytogenetic impact could not be investigated.…”

“…[1][2][3][4][5][6][7][8] In comparison to standard myeloablative conditioning regimen, reduced-intensity conditioning regimen resulted in lower non-relapse mortality (NRM) but also in a higher risk of relapse. 9 Retrospective studies suggest that the intensity of the conditioning regimen correlates with the risk of relapse.…”

Graft-versus-myeloma effect following antithymocyte globulin-based reduced intensity conditioning allogeneic stem cell transplantation

“…43,44 As of June 2002, 105 MM patients who received a RIC allo-SCT have been reported, 45 with further evidence in other publications that the use of RIC allo-SCT for MM is rapidly growing. 30,[46][47][48] However, issues related to TRM rate, GVHD incidence, and proof of a GVM effect are still unresolved because of considerable heterogeneity in patient selection criteria, conditioning regimens, timing of RIC allo-SCT (after autologous transplantation, in complete or partial remission, or after relapse), and comorbid conditions (age and exclusion criteria due to other organ dysfunction). In the series of RIC allo-SCT for MM reported by Badros et al, 28 TRM in the first 100 days was 10% comparing favorably with results obtained in the myeloablative setting from the same institution.…”

Is there still a role for allogeneic stem-cell transplantation in multiple myeloma?

“…[22][23][24] Two German studies and a study from the MD Anderson center confirmed 2-year survivals of 26-50% for patients who had failed one or more autologous transplants. A study combining data from several centers, including approximately 120 patients, found that relapse from a prior autologous transplant was the most significant risk factor for transplant mortality (HR 2.80; P = 0.02), relapse (HR 4.14; P < 0.001), and death (HR 2.69; P = 0.005).…”

“…[21] Several other studies of reduced-intensity allografts from family members or unrelated donors have confirmed that results are poor when patients have failed a prior autologous transplant or have chemotherapy-resistant disease. [22][23][24] Two German studies and a study from the MD Anderson center confirmed 2-year survivals of 26-50% for patients who had failed one or more autologous transplants. A study combining data from several centers, including approximately 120 patients, found that relapse from a prior autologous transplant was the most significant risk factor for transplant mortality (HR 2.80; P = 0.02), relapse (HR 4.14; P < 0.001), and death (HR 2.69; P = 0.005).…”