Impact of Genetic Abnormalities After Allogeneic Stem Cell Transplantation in Multiple Myeloma: Report of the Societe Francaise De Greffe De Moelle Et De Therapie Cellulaire.

Del (13q), t (4;14) and del (17p) are well-recognized poor prognostic genetic abnormalities in multiple myeloma after standard chemotherapy and autologous stem cell transplantation (SCT). We investigated the prognostic impact of these genetic abnormalities, detected by fluorescence in situ hybridization (FISH), on the outcome in patients who underwent allogeneic SCT.

This is a retrospective study performed in 20 centres for a total of 175 patients, using the database register of the SFGM-TC and the cytogenetic files of the IFM and MAG groups. The median age of the population at diagnosis was 51 years (range, 28-62 years). FISH analysis was performed either at diagnosis or at relapse before allograft. Chromosomal abnormalities were found in 127 of 175 patients (73%), distributed as follows (in percent of patients evaluable for each abnormality): 59% for del (13q), 26% for t (4;14), 25% for del (17p), 24% for t (11;14) and 4% for t (14;16). Béta2microglobuline was superior to 4 mg/L in 51% and more than 92% had received at least one prior high-dose therapy followed by autologous SCT. Forty percent of patients were transplanted in the first course of the disease. Most patients (79%) received two or less lines of treatments before transplantation. Prior treatments included thalidomide and bortezomib in, respectively, 25% and 27% of cases. At transplant, 12% of patients were in complete response (CR), 6% in very good partial response (VGPR), 66% in partial response (PR), 8% in stable disease (SD) and 8% in progressive disease (PD). The median time from diagnosis to transplant was 15 months (range, 4-175 months). Seventy seven percent of patients received reduced conditioning regimen, including antithymoglobulin (ATG) in 52% of cases. Peripheral blood and bone marrow were used as the source of cells in 78% and 19%, respectively. Most donors (69%) were match related donors.

Best response to transplant was CR, VGPR, PR, SD and PD in, respectively, 38%, 12%, 33%, 7% and 10% (among 130 patients with available data). With a median follow-up of 36 months, the 3-year progression free survival (PFS) and overall survival (OS) were 34% and 52%, respectively. Three-year post-transplant progression occurred in 53%. One-year transplant-related mortality (TRM) was 21%. Grade II to IV acute graft-versus-host disease (GvHD) was present in 33%. Limited and extensive chronic GvHD occurred respectively in 16% and 23% of evaluable patients. In univariate analysis, del (13q), t (4;14) and del (17p) had no impact on the PFS, OS and progression. Three-year PFS and OS were, respectively, 39% and 53% for del (13q), 29% and 38% for del (17p), 26% and 38% for t (4;14), 25% and 43% for t (11;14), 31% and 45% for the group of patients without any of these cytogenetic abnormalities. Patients transplanted in the first course of the disease with t (4;14) (n=14) and with del (17p) (n=6) had a 3-year PFS of 36% and 44%, respectively. In multivariate analysis, better PFS was significantly associated with younger age (P= 0.02, HR=1.1), sensitive disease status at transplant (P=0.04, HR=0.55) and two or less prior lines of treatments (P<0.001, HR=0.3); better OS was associated with younger age and two or less prior lines of treatments (respectively, P=0.01, HR=1.1; and P=0.02, HR=0.5).

These data suggest no impact of genetic abnormalities after allogeneic SCT for multiple myeloma and did not confirm the encouraging results of allogeneic SCT for t (4;14) myeloma (Schilling et al., Leukemia, 2008). More studies are warranted to better define the possible role of early allograft in poor prognostic myeloma and to further develop risk-adapted strategy based on cytogenetics.

No relevant conflicts of interest to declare.