Upfront autologous transplantation still improving outcomes in patients with multiple myeloma
Mené au Royaume-Uni sur 281 patients atteints d'un myélome multiple récemment diagnostiqué, cet essai de phase II évalue la non infériorité, du point de vue de la proportion de patients obtenant une très bonne réponse partielle après la phase d'induction et du point de vue du taux de survie sans progression à 2 ans, et la toxicité d'une stratégie thérapeutique de première ligne comportant du carfilzomib en traitement d'induction, de consolidation et d'entretien par rapport à une stratégie comportant le même traitement d'induction suivi d'une greffe autologue de cellules souches hématopoïétiques
High-dose melphalan followed by autologous haematopoietic stem-cell transplantation (HSCT) has been the standard-of-care in multiple myeloma treatment for the past 30 years. However, with increasingly potent triplet regimens leading to improved response rates after induction, the need for autologous HSCT is increasingly questioned. Its role has been evaluated in four important randomised clinical trials. In the EMN02/HO95 study, induction therapy consisted of bortezomib–cyclophosphamide–dexamethasone before randomisation to either bortezomib–melphalan–prednisone or autologous HSCT. 1 The similar GIMEMA study compared six consolidation cycles of lenalidomide–cyclophosphamide–dexamethasone with two courses of high-dose melphalan and autologous HSCT. 2 The introduction of the potent dual proteasome inhibitor-immunomodulatory drug (PI-IMID) bortezomib–lenalidomide–dexamethasone regimen prompted both the IFM 2009 trial and the DETERMINATION trial. 3 , 4 The IFM trial was completed earlier than the DETERMINATION trial as the maintenance lenalidomide after consolidation was only administered for 1 year, unlike the DETERMINATION trial in which it was administered until disease progression. In all four of these important randomised clinical trials, progression-free survival was superior in people who received autologous HSCT than in people who received chemotherapy. However, except for the EMN02/HO95 study, deferring autologous HSCT was not found to adversely affect overall survival (table). Replacing bortezomib with carfilzomib, the GIMEMA group performed the FORTE study, which compared three pathways: carfilzomib–lenalidomide–dexamethasone (KRd) with autologous HSCT, KRd without autologous HSCT, and carfilzomib–cyclophosphamide–dexamethasone (KCd) with autologous HSCT. 5 KRd was superior to KCd, with an at least very good partial response rate of 70% compared with 53% after four cycles (odds ratio 2·14, 95% CI 1·44–3·19, p=0·0002). After a median follow-up of 51 months, the sustained minimal residual disease (MRD) negativity rate was superior in the KRd with autologous HSCT group, which also led to a progression-free survival benefit.