Umbilical Cord Blood Transplantion In Relapsed Multiple Myeloma

In patients with relapsing multiple myeloma (MM), treatments with lenalinomide and dexamethasone provides a median overall survival of 36 months. As all patients will relapse, allogenic transplantation with adult donor stem cells may provide long-term disease control. Only few cases of umbilical cord blood transplant (UCBT) have been reported in patients with relapsing MM so far. We report for the first time, the outcome of 17 consecutive patients with relapsing MM who underwent UCBT at a single institute between 2005 and 2009.

Median age was 58 years [41–66]. All patients had relapsed before transplantation with a median of 2 relapses (range 1–4). They were all treated with bortezomib (5/17), bortezomib and thalidomide (7/17) or lenalidomide (5/17) as salvage therapy before tranplant. Five patients were in complete remission (CR) before transplant, 4 in very good partial response (VGPR), 7 in partial response (PR) and 1 was in progression. 16 patients received two cord-blood units and one patient received only one. All patients received reduced intensity conditioning (RIC) regimen (fludarabine, cyclophosphamide, low dose total body irradiation +/− melphalan).

Neutrophil count ≥ 0.5 × 10⁹/L for 5 consecutive days was achieved in 16/17 patients within a median of 10 days [6–35] and platelet count ≥ 50 × 10⁹/L for five consecutive days in 12/17 patients within a median of 46 days [27–216]. T-cell chimerism (TCC) below 1% from the recipient was obtained in 16/17 patients. Among the 5 patients in CR before UCBT, 4 are still in CR and healthy (Performans status 0 or 1, limited chronic GVH disease in 3/4 patients) at follow-up (month +17, +18, +31, +54). For 2 of these patients, the CR was confirmed by flow cytometry (£ 1 tumor plasma cell per 5–10000 normal plasma cells in the bone marrow). The remaining patient in CR before transplantation relapsed at 41 months. Among the 12 patients that were not in CR at UCBT, 5 achieved the CR criteria at a median of 4 months after UCBT. The CR rate post-UCBT was 58%. These data are strongly in favor of a cord blood versus myeloma effect. Unfortunately, among the 5 patients whose response was upgraded to CR by UCBT, 1 underwent TRM and 4 relapsed after a median of a year post UCBT. For the 10 patients in CR post transplant, the risk of relapse, was statistically lower (Fisher Exact Test, p=0,048) for patients already being in CR before transplant (relapse rate: 1/5) than for patients who obtained CR after transplant (relapse rate: 4/4 taking into account that the 5^th patient was not at risk because of early TRM). Overall, 53 % of patients relapsed or had progressive disease. A treatment with lenalidomide (alone or associated with dexamethasone) was unable to control disease evolution post UCBT. 24% of patients died from relapse or progression. 29 % of patients underwent TRM (within the first 6 months for the majority). TRM was mainly due to infections (2 bacterial septic shocks and 3 invasive fungal infections). With a median follow-up of 20 months, 47 % of patients are alive. The one year overall survival was 58 % and one year event free survival 41 %. Median overall survival estimated by Kaplan-Meier method was 30 mo. [14–46] (95% CI) after D0 of UCBT. At follow-up, the performans status of survivors was PS=0 (4/8), PS=1 (2/8) and PS=2 (2/8).

This study indicates that RIC regimen followed by UCBT is feasible in patients with relapsed MM with a TRM of 29% and a high CR rate (58%) in favour of a cord blood versus myeloma effect. The best benefit from transplant was obtained for patients in CR before UCBT who obtained long term remissions together with limited GVH disease and a good performans status.

Rossi: SANOFI-AVENTIS, LFB, INNATE PHARMA: Consultancy.