Anti-BCMA/GPRC5D bispecific CAR T cells for relapsed or refractory multiple myeloma: is 1+1 greater than 2?
Mené sur 24 patients atteints d'un myélome multiple réfractaire ou récidivant (âge médian : 62 ans ; durée médiane de suivi : 5,8 mois), cet essai de phase I détermine la dose maximale tolérée d'une immunothérapie à base de lymphocytes CAR-T bispécifiques ciblant BCMA et GPRC5D puis évalue son efficacité du point de vue du taux de réponse globale
In the past 5 years, with the advent and development of chimeric antigen receptor (CAR) T-cell therapy, treatment landscapes for relapsed or refractory multiple myeloma have been revolutionised. The first milestone was reached as recently as 2019, when Raje and colleagues 1 reported the initial promising results of anti-B-cell maturation antigen (BCMA) CAR T-cell therapy bb2121 in the phase 1 CRB-401 trial, which showed an overall response rate of 85% (28 of 33 patients; 15 [45%] with complete response) with a median progression-free survival of 11·8 months (95% CI 6·2–17·8) in the first 33 patients with relapsed or refractory multiple myeloma. In the phase 2 KarMMa study (n=128), 2 bb2121 led to an overall response rate of 73% (94 of 128 patients; 42 [33%] with complete response or better) and a median progression-free survival of 8·8 months (95% CI 5·6–11·6) as well as good safety profiles, with cytokine release syndrome (CRS) in 107 (84%) patients (100 [78%] grade 1–2) and neurological toxicities in 23 (18%) patients (19 [15%] grade 1–2). The remarkable success promoted the approval of bb2121 in the treatment of relapsed or refractory multiple myeloma by the US Food and Drug Administration (FDA) in 2021. In June, 2021, the dual epitope-binding anti-BCMA CART-cell therapy ciltacabtagene autoleucel (cilta-cel), formerly also known as LCAR-B38M and JNJ-68284528, led to an overall response rate of 97% (94 of 97 patients; 65 [67%] with stringent complete response or better) and 12-month progression-free survival of 77% (95% CI 66·0–84·3), with CRS in 92 (95%) patients (87 [91%] grade 1–2) and neurological toxicities in 20 (21%) patients (10 [10%] grade 1–2) in the phase 1b/2 CARTITUDE-1 trial (n=97). 3 These data formed the basis for the approval of cilta-cel in the treatment of relapsed or refractory multiple myeloma by the FDA in 2022.