Another quadruplet therapy for multiple myeloma: the beginning of the end for autologous haematopoietic stem-cell transplantation?
Mené sur 50 patients atteints d'un myélome multiple récemment diagnostiqué et éligibles à une greffe (âge médian : 59 ans), cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse complète, et la toxicité d'un traitement combinant isatuximab, carfilzomib, lénalidomide et dexaméthasone
In the past 15 years, treatment frameworks for newly diagnosed multiple myeloma have radically changed. It is important to recall that as recently as 2010, Rajkumar and colleagues 1 presented ECOG E4A03, which was a phase 3 trial examining the role of lenalidomide, combined with two different dosing regimens for dexamethasone, that showed a 68% overall response rate (ORR; 10% complete remission rate) after four cycles of therapy, a result considered to be astounding at the time. Fast forward to 2024, the use of triplet induction has nearly been supplanted by four component regimens, typically including an immunomodulatory drug, a proteasome inhibitor, a steroid, and the newest addition, an anti-CD38 antibody. Trials such as GRIFFIN 2 and now PERSEUS 3 using the combination of lenalidomide, bortezomib, dexamethasone, and daratumumab, and the MASTER trial 4 testing the combination of carfilzomib, lenalidomide, dexamethasone, and daratumumab, have led to the expectation that regimens for newly diagnosed multiple myeloma need to offer an ORR in excess of 90%. Furthermore, Kaiser and colleagues (NCT03188172) investigated a quintuplet regimen for the treatment of ultra-high risk multiple myeloma, including plasma cell leukaemia. However, all of these trials incorporate high dose melphalan with autologous haematopoietic stem-cell transplantation (HSCT), which is an intervention that has come into question with the publication of the DETERMINATION trial 5 results that suggested, after a median follow-up of 78 months, HSCT did not improve overall survival (an outcome, however, this study was not powered to analyse). Moreover, some investigators have raised concerns that mutagenesis of haematopoietic DNA caused by high dose melphalan could be an important factor associated with the development of secondary malignancies among patients with multiple myeloma who undergo HSCT.