Double Autologous Transplant Versus Tandem Autologus - Non Myeloablative Allogeneic Transplant for Newly Diagnosed Multiple Myeloma.

Allogeneic approaches employing low dose TBI nonmyeloablative conditionings reported a dramatic reduction of transplant-related mortality (TRM) compared to conventional high dose regimens in newly diagnosed multiple myeloma (MM) (Maloney et al, Blood, 2003). The role of allografting, however, compared to autologous HCT remains to be determined. From September 1999 to July 2004, 241 consecutive MM patients, up to the age of 65, were diagnosed at five academic Italian Institutions. Overall, 194/241 had natural siblings (Table 1): 158/194 (81%) were HLA typed, while 36/194 (19%) were not typed for the following reasons: patients not eligible for high dose chemotherapy (n. 14); siblings not eligible for peripheral hematopoietic cell (PHC) donation (n.11); patient refusal to high dose chemotherapy (n. 9), unknown (n.2). Seventy-six/158 (48%) with a matched donor were offered a tandem autologous- nonmyeloablative allogeneic HCT approach. Eventually, 56/76 (73%), the “auto-allo group”, were enrolled while 20 did not enter the tandem program as 5 siblings (5/76, 7%) were not eligible for PHC donation, 5 patients refused an allogeneic HCT, and 10 patients preferred allografting as a possible salvage treatment. Of 102 patients without matched donors or after refusal to allografting, 73, “double-auto group”, underwent a standard double autologous transplant while 29 received less intense treatments because of clinical conditions or patient preference.

After induction chemotherapy, patients of both groups underwent G-CSF mobilised autografting with high dose melphalan (200 mg/m2). In the “auto-allo” group, the autologous HCT was followed, 2-4 months later, by low dose (2.0 Gy) TBI, allogeneic PHC infusion, and post transplant mycophenolate mofetil and cyclosporin. In the “double-auto group”, patients received a second autologous HCT. Patients characteristics were as follows: age: 54 (range 34–65) vs 53 (range 33–64) (p=ns); stage III myeloma: 77% vs 64% (p=0.03); beta 2 microglobulin > 2,5 mg/dl: 75% vs 59% (p=0.005), for the “auto-allo group” and for “the double-auto group”, respectively. At the time of this analysis, 56/56 of the “auto-allo group” and 55/73 of “the double-auto group” had completed the transplant programs. After median follow up of 3 years (range 11–80 months), TRM was 11% vs 4% (p=0.09); complete remission rates, defined as the disappearance of the monoclonal paraprotein by immunofixation, were 46% vs 16% (p=0.0001); overall survivals were 84% versus 62% (p=0.003); progression free survivals were 75% vs 41% (p=0.00008); event free survivals were 61% (34/56)% vs 38% (30/73) (p=0.006) in the “auto-allo group” and in the “double-auto” group, respectively. Longer follow up is needed, however data suggest that the “auto- non myeloablative allo” approach is not inferior to “double autologous” HCT in newly diagnosed MM.