Newly diagnosed multiple myeloma patients treated with tandem auto‐allogeneic stem cell transplant have better overall survival with similar outcomes at time of relapse compared to patients who received autologous transplant only

Abstract

Background: Long-term survival in patients progressing after tandem autologousallogeneic stem cell transplant (SCT) has been reported, suggesting a persistent graftvs-myeloma (GvM) effect even after post-transplant progression. Methods: In order to confirm this observation, we updated the results of our previously published cohort of 92 newly diagnosed myeloma patients who received tandem transplant and compared them with 81 contemporary patients who received autologous transplant only. Results: With a median follow-up of 13.1 and 10.2 years, respectively, median overall survival (OS) in the tandem group has not been reached, compared with 6.1 years after auto-SCT (P ≤ .001). Disease progression occurred less frequently after tandem transplant, with an estimated 10-year cumulative incidence of 49% vs 76% (P ≤ .001). Cumulative incidence of extensive chronic graft-vs-host disease (cGVHD) was high at 83%, with modest benefits on OS (60% vs 49%, P = .550) but sharp improvement of progression-free survival (PFS; 55% vs 10%, P = .002) at 10 years associated with development of cGVHD. After first progression, median OS was 5.8 years in tandem and 5.2 years in the auto-group (P = .062); median PFS was also similar. Conclusion: Despite confirmation of better outcomes after upfront tandem transplant, our data do not support persistence of a strong, clinically significant graft-vsmyeloma effect after first progression, emphasizing the need to better characterize the GvM effect.

Allogeneic Stem Cell Transplantation in Multiple Myeloma

“…In the following years, myeloablation achieved through high-dose chemotherapy and auto-SCT with maximal reduction of MM-cells was separated from allo-SCT with less myelosuppressive but highly immunosuppressive reduced-intensity conditioning (RIC) regimens to prevent treatment-related organ toxicities but allow a sufficient engraftment and GvM effect [ 23 ]. Several prospective trials demonstrated improved OS and PFS after this auto/allo-SCT approach with RIC in the first-line setting as compared to the control arm, mostly tandem auto-SCT, and randomization according to the availability of a human leukocyte antigen (HLA)-identical donor [ 24 , 25 , 26 ] ( Table 1 ). In two studies, prolonged PFS was shown at least in patients with HR cytogenetics [ 4 , 27 , 28 , 29 ] and no study demonstrated inferiority of the auto/allo-SCT arm [ 30 , 31 , 32 , 33 , 34 ], suggesting that HR constellations may be overcome by the allo-SCT.…”

“…However, some trials showing superior PFS but similar OS indicate that the increased TRM may probably counteract the benefit of a reduced relapse rate by allo-SCT [ 29 ]. TRM-rates remained as substantial with 20% at 10 years [ 35 ], but were not worse as compared to the auto-SCT control arm in more than half of the studies [ 24 , 25 , 26 , 28 , 29 , 32 ]. The leading cause of death was organ failure or an infectious complication and in only 6% GvHD [ 17 , 29 ].…”

“…A pooled analysis of four prospective trials conducted in the first-line setting demonstrated an enhanced post-relapse survival after auto/allo-SCT as compared to a tandem auto-SCT [ 35 , 44 ], indicating a sustained immunological effect. However, this difference was not observed in a fifth prospective first-line trial [ 26 ], and not in case of HR cytogenetics [ 29 ]. The addition of novel agents, in particular IMID and PI, in the induction therapy and after allo-SCT was identified as a beneficial prognostic factor in several retrospective analyses [ 44 , 74 , 79 , 80 ], and response to PI and IMID was similar no matter if these substances were applied in pre- or post-transplant settings [ 75 ].…”

Current Role of Allogeneic Stem Cell Transplantation in Multiple Myeloma

“…The standard graft-versus-host prophylaxis used in Hovon-50 [62], Italian study [26], BMT CTN [30], and NMAM2000 [28] is cyclosporine in combination with mycophenolate mofetil. In contrast, PETHEMA investigators were using cyclosporine with methotrexate [25] and other groups tacrolimus with mycophenolate mofetil or methotrexate [14,63]. On average, an extensive or moderate-severe chronic GVHD incidence of 40-70% has been reported in these trials.…”