Superiority of Double over Single Autologous Stem Cell Transplantation as First-Line Therapy for Multiple Myeloma.
Antonio De Vivo1,*,
Roberto Massimo Lemoli1,*,
Sante Tura1,* and
(Intr. by Michele Baccarani)1 Institute of Hematology and Medical Oncology "Seragnoli", University of Bologna, Bologna, Italy.
The "Bologna 96" clinical trial was designed in an attempt toprospectively compare a single autologous transplantation (Tx-1)versus double autologous transplantation (Tx-2) as part of first-linetherapy for patients with symptomatic multiple myeloma (MM)and less than 60 years of age. Tx-1 was given to support melphalan200 mg/m2 (MEL-200); Tx-2 was given to support a first courseof MEL-200 followed, within 3 to 6 months, by melphalan 120mg/m2 + busulfan 12 mg/kg. In both arms of the study, autologoustransplantation was preceded by 4 courses of VAD and subsequentcollection of peripheral blood stem cells with high-dose cyclophosphamide7 g/m2. An analysis was performed using an intent-to-treat approachon 228 patients who were randomly assigned to Tx-1 (n=115 patients,median follow-up of living patients: 45 months) or Tx-2 (n=113patients, median follow-up of living patients: 54 months). Incomparison with Tx-1, Tx-2 prolonged event-free survival (EFS)of 12 months (P=0.001) and time to progression (TTP) of 17 months(P=0.0001). Six-year projected probability of survival (OS)was 44% for Tx-1 and 63% for Tx-2 (P=0.3). The probability ofattaining stringently defined complete remission (CR) or nearcomplete remission (nCR) was 35% for Tx-1 and 48% for Tx-2;the sample size analyzed was not powered to detect a statisticallysignificant difference between the two groups. Among patientsrandomized to Tx-1, attainment of CR or nCR was an essentialprerequisite for extended OS (P=0.0001), EFS (P=0.000002) andTTP (P=0.000007). At the opposite, the benefits of double autologoustransplantation were the greatest among patients who failedat least nCR. In particular, patients who did not attain CRor nCR after the first autologous transplantation and by studyrandomization received a second transplantation had a significantlylonger duration of OS (P=0.01), EFS (P=0.000006) and TTP (P=0.000001)than patients who had the same response status but were assignedto receive a single autologous transplantation. Compared toTx-1, Tx-2 significantly extended OS (P=0.04), EFS (P=0.000006)and TTP (P=0.000001) also among patients who failed Cr or nCRafter receiving the entire treatment program to whom they wereassigned (Tx-1 or Tx-2). At the opposite, for patients who werein CR or nCR after the first transplantation, there was no significantbenefit from receiving a second autologous transplantation.In conclusion, data from the present analysis show that in comparisonwith a single autologous transplantation, i) double transplantationsignificantly prolonged EFS and TTP among younger (< 60 years)patients with previously untreated MM; ii) double autologoustransplantation was of particular benefit for patients who failedat least nCR. Mature data derived from the final analysis ofthe study must be awaited before definite conclusions can begiven concerning the impact of double autologous transplantationon the outcome of patients with MM. Supported by Universitàdi Bologna, Progetti di Ricerca ex-60% (M.Cavo); Ministero dellUniversitàe Ricerca Scientifica, progetto FIRB, RBAU012E9A_001 (M. Cavo);and Fondazione Carisbo.