TY - JOUR
T1 - Salvage therapies including retreatment with BCMA-directed approaches after BCMA CAR-T relapses for multiple myeloma
AU - Reyes, Kevin R.
AU - Liu, Yen Chun
AU - Huang, Chiung Yu
AU - Banerjee, Rahul
AU - Martin, Thomas
AU - Wong, Sandy W.
AU - Wolf, Jeffrey L.
AU - Arora, Shagun
AU - Shah, Nina
AU - Chari, Ajai
AU - Chung, Alfred
N1 - Publisher Copyright:
© 2024 by The American Society of Hematology.
PY - 2024/5/14
Y1 - 2024/5/14
N2 - For patients with relapsed/refractory multiple myeloma with a relapse after B-cell maturation antigen (BCMA)–directed chimeric antigen receptor T-cell therapy (CAR-T), optimal salvage treatment strategies remain unclear. BCMA-directed CAR-T and bispecific antibodies (BsAbs) are now commercially available, and the outcomes for retreatment with BCMA-directed approaches are not well studied. We performed a retrospective analysis of 68 patients with relapsed disease after BCMA-directed CAR-T to evaluate outcomes and responses to salvage therapies. With a median follow-up of 13.5 months, median overall survival from time of relapse until death was 18 months (95% confidence interval [CI], 13.2 to not reached [NR]). Fifty-eight patients received subsequent myeloma-directed therapies, with a total of 265 lines of therapy (LOTs). The overall response rate for firstline salvage therapy was 41% (95% CI, 28-55). Among all LOTs, high response rates were observed among those receiving another BCMA-directed CAR-T (89%), BCMA-directed BsAbs (60%), CD38-directed combinations (80% when combined with BsAb; 50% when combined with immunomodulatory drugs and/or proteasome inhibitors), and alkylator-combinations (50% overall; 69% with high-dose alkylators). Thirty-four patients received at least 1 line of salvage BCMA-directed therapy; median progression-free survival was 8.3 months (95% CI, 7.9 to NR), 3.6 months (95% CI, 1.4 to NR), and 1 month (95% CI, 0.9 to NR) with median duration of response (DOR) of 8 months, 4.4 months, and 2.8 months for subsequent BCMA-directed CAR-T, BsAb, and belantamab mafadotin, respectively. Retreatment with BCMA-directed CAR-T and BsAbs can be effective salvage options after BCMA-directed CAR-T relapse; however, DORs appear limited, and further studies with new combinations and alternative targets are warranted.
AB - For patients with relapsed/refractory multiple myeloma with a relapse after B-cell maturation antigen (BCMA)–directed chimeric antigen receptor T-cell therapy (CAR-T), optimal salvage treatment strategies remain unclear. BCMA-directed CAR-T and bispecific antibodies (BsAbs) are now commercially available, and the outcomes for retreatment with BCMA-directed approaches are not well studied. We performed a retrospective analysis of 68 patients with relapsed disease after BCMA-directed CAR-T to evaluate outcomes and responses to salvage therapies. With a median follow-up of 13.5 months, median overall survival from time of relapse until death was 18 months (95% confidence interval [CI], 13.2 to not reached [NR]). Fifty-eight patients received subsequent myeloma-directed therapies, with a total of 265 lines of therapy (LOTs). The overall response rate for firstline salvage therapy was 41% (95% CI, 28-55). Among all LOTs, high response rates were observed among those receiving another BCMA-directed CAR-T (89%), BCMA-directed BsAbs (60%), CD38-directed combinations (80% when combined with BsAb; 50% when combined with immunomodulatory drugs and/or proteasome inhibitors), and alkylator-combinations (50% overall; 69% with high-dose alkylators). Thirty-four patients received at least 1 line of salvage BCMA-directed therapy; median progression-free survival was 8.3 months (95% CI, 7.9 to NR), 3.6 months (95% CI, 1.4 to NR), and 1 month (95% CI, 0.9 to NR) with median duration of response (DOR) of 8 months, 4.4 months, and 2.8 months for subsequent BCMA-directed CAR-T, BsAb, and belantamab mafadotin, respectively. Retreatment with BCMA-directed CAR-T and BsAbs can be effective salvage options after BCMA-directed CAR-T relapse; however, DORs appear limited, and further studies with new combinations and alternative targets are warranted.
KW - Despite high response rates, durability of responses to salvage therapies after BCMA-directed CAR-T relapses are currently suboptimal
KW - Retreatment with BCMA-directed therapies after prior BCMA-directed CAR-T can elicit high response rates in patients with multiple myeloma
UR - http://www.scopus.com/inward/record.url?scp=85189805199&partnerID=8YFLogxK
U2 - 10.1182/bloodadvances.2023012066
DO - 10.1182/bloodadvances.2023012066
M3 - Article
C2 - 38429087
AN - SCOPUS:85189805199
SN - 2473-9529
VL - 8
SP - 2207
EP - 2216
JO - Blood advances
JF - Blood advances
IS - 9
ER -