New Strategy for Allogeneic Peripheral Blood Stem Cell Transplantation After Reduced Intensity Conditioning in Multiple Myeloma: Interim Analysis of the IFM2005-03 Study.

The development of new agents with potent anti-tumor activity has considerably improved the survival of multiple Myeloma (MM) patients. However, there is still a high risk of relapse mainly due to the inability of these agents to cure and eliminate definitively the MM cells. Allografting remains the only available curative treatment particularly for patients with high risk factors.

This is an interim analysis of a prospective multicenter study for MM patients of age ≤ 65 years receiving reduced intensity conditioning (RIC) followed by allogeneic peripheral blood stem cell transplantation (allo-PBSCT) after achieving at least a partial response (PR) to auto-transplantation in first line. Patients previously received either VAD or VD as induction treatment followed by Melphalan 200 mg/m². Patients must have an HLA identical donor either from siblings or unrelated 10/10 HLA donors, and at least one of the following poor prognostic factors (PPF) : β2 microglobulin >3mg/L, Del 13, t(4;14) and Del 17p. The conditioning regimen combined Fludarabine 30 mg/m²/d (d-5□d-1), Busilvex IV 3,2 mg/kg/d (d-4, d-3) and ATG 2,5 mg/kg/d (d-2, d-1). By day 90 post-allograft, a response assessment was done, patients not in CR received 4 cycles of Velcade 1.3 mg/kg, and after Velcade, if the CR was not achieved, increasing doses of donor lymphocyte infusions (DLI) were administered. This analysis included 11 patients, 9 males and 2 females, median age was 46 years [40-60], there were 8 IgG stageA (7κ & 1λ) and 3 IgA (1κ stage B & 2λ stage A). There were 3 patients with 1 PPF, 5 patients with 2 PPF and 3 patients with 3 PPF.

Seven patients received 4 cycles of VAD (4 patients VAD+DCEP), 1 patient received 4 cycles of Velcade + dex. and 3 patients received other combinations (1PAD, 2VAD then Velcade). After induction, 7 patients were in PR and 4 in stable disease (SD). Patients received auto-HSCT after a median time of 6.6 months [4.5-8.7] from diagnosis. All patients were in PR after auto-HSCT and before allo-PBSCT. The median number of infused CD34+ cells was 6.5 ×10⁶/kg [2.6-13.7] from 4 identical siblings and 7 matched unrelated donors. Sex matching was: F□M:4, F□F:1, M□F: 1 and MμM:5. At D90, 3 patients were in CR and 8 patients received Velcade after absence of CR (2 VGPR and 6 PR). After Velcade, the 2 VGPR evolved to CR and patients in PR became 1 CR, 1 VGPR and 4 remained in PR). One patient in VGPR and 3 in PR received DLI after Velcade, responses were: 1 VGPR and 3 patients progressed. There were 6 acute GVHD (5 grade II and 1 grade III) and 6 chronic GVHD (5 limited and 1 extensive), all GVHD were resolved at the last follow-up. After a median follow-up of 30 months, all patients are alive [100% overall survival (O.S.)], 3 patients are in CR, 3 in VGPR, 4 in PR and one in relapse without any active chronic GVHD even after DLI administration.

We showed completely different results from the IFM99-03 study in terms of O.S. and toxicity, this difference was due to the better conditioning with the introduction of Busilvex, also the impact of Velcade in eliminating the residual disease. According to these very promising results, we should reconsider the allo-HSCT as a first line treatment for MM especially for patients with PPF using either RIC or standard conditioning depending on age.

No relevant conflicts of interest to declare.