PURPOSE OF REVIEWThe introduction of bispecific antibodies is one of the most significant recent advances in the treatment of relapsed/refractory multiple myeloma. This review will summarize the management of the toxicities associated with newly approved T cell-engaging bispecific antibodies and those which may be approved in the near future.RECENT FINDINGSNumerous trials have shown that bispecific antibodies can be both effective and tolerable when adverse events are properly managed. Cytokine release syndrome and increased infections are observed across all bispecific antibodies. Additional adverse events are target-specific, such as the more severe hypogammaglobulinemia and infections of BCMA bispecific antibodies and the dysgeusia, nail dystrophy, and skin changes of GPRC5D bispecific antibodies. Bispecific antibodies will surely become a mainstay of multiple myeloma therapy given their efficacy and accessibility. Their unique toxicities must be carefully considered and managed to ensure they are utilized safely.

2023-11-01·Blood Cancer Discovery

IVIg Use Associated with Ten-Fold Reduction of Serious Infections in Multiple Myeloma Patients Treated with Anti-BCMA Bispecific Antibodies

Article

作者: Thibaud, Santiago ; Lurie, Alaina ; Avery, Lisa ; Cho, Hearn Jay ; Parekh, Samir S ; Sanchez, Larysa J ; Lancman, Guido ; Kotlarz, Krzysztof ; Jagannath, Sundar ; Parsa, Kian ; Chari, Ajai ; Lieberman-Cribbin, Alex ; Rossi, Adriana ; Richard, Shambavi ; Richter, Joshua ; Rodriguez, Cesar

AbstractBCMA-targeted bispecific antibodies (BiAb) are efficacious in relapsed/refractory multiple myeloma; however, serious infections have emerged as important toxicities. In this retrospective study, we characterized all infections and their risk factors, and evaluated the impact of infection prophylaxis in patients treated with BCMA-targeted BiAbs. Among 37 patients, 15 (41%) experienced a grade 3–5 infection, with two infection-related deaths during deep remissions. Most (84%) infections occurred during disease remissions. The cumulative probability of grade 3–5 infection increased over time with no plateau. Among responders (n = 26), profound hypogammaglobulinemia occurred in 100% and continued throughout the entire duration of treatment. During periods when patients were receiving intravenous immunoglobulin (IVIg), the rate of grade 3–5 infections was 90% lower than during observation (incidence rate ratio, 0.10; 95% confidence interval, 0.01–0.80; P = 0.0307). No other risk factors for infection were identified. This study demonstrates that profound hypogammaglobulinemia is universal with BCMA-targeted BiAbs, with intravenous immunoglobulin potentially abrogating most of the infection risk.Significance:To the best of our knowledge, this is the first study to comprehensively analyze risk factors and mitigation strategies to prevent infections in myeloma patients receiving anti-BCMA bispecific antibodies. Profound and prolonged hypogammaglobulinemia was universal among responders, while immunoglobulin replacement was associated with 90% lower rates of grade 3–5 infections.See related commentary by Garfall and Stadtmauer, p. 427 .This article is featured in Selected Articles from This Issue, p. 419

2022-07-01·Molecular Therapy1区 · 医学

Locally secreted BiTEs complement CAR T cells by enhancing killing of antigen heterogeneous solid tumors

1区 · 医学

Article

作者: Zhang, Jiasi Vicky ; Thokala, Radhika ; Kainth, Devneet ; Liang, Hongsheng ; Zhang, Xiangtong ; Zhang, Logan ; Zhao, Yang ; Yin, Yibo ; O'Rourke, Donald M ; Haddad, Leila ; Long, Yu ; Logun, Meghan T ; Nasrallah, MacLean P ; Wu, Tong ; Li, Nannan ; Johns, Emily X ; Qi, Jiping ; Lin, Zhiguo ; Rodriguez, Jesse L ; Hu, Li ; Binder, Zev A

Bispecific T cell engagers (BiTEs) are bispecific antibodies that redirect T cells to target antigen-expressing tumors. We hypothesized that BiTE-secreting T cells could be a valuable therapy in solid tumors, with distinct properties in mono- or multi-valent strategies incorporating chimeric antigen receptor (CAR) T cells. Glioblastomas represent a good model for solid tumor heterogeneity, representing a significant therapeutic challenge. We detected expression of tumor-associated epidermal growth factor receptor (EGFR), EGFR variant III, and interleukin-13 receptor alpha 2 (IL13Rα2) on glioma tissues and cancer stem cells. These antigens formed the basis of a multivalent approach, using a conformation-specific tumor-related EGFR targeting antibody (806) and Hu08, an IL13Rα2-targeting antibody, as the single chain variable fragments to generate new BiTE molecules. Compared with CAR T cells, BiTE T cells demonstrated prominent activation, cytokine production, and cytotoxicity in response to target-positive gliomas. Superior response activity was also demonstrated in BiTE-secreting bivalent T cells compared with bivalent CAR T cells in a glioma mouse model at early phase, but not in the long term. In summary, BiTEs secreted by mono- or multi-valent T cells have potent anti-tumor activity in vitro and in vivo with significant sensitivity and specificity, demonstrating a promising strategy in solid tumor therapy.

100 项与 Anti-BCMA anti-CD38 bispecific chimeric antigen receptor T cell therapy(Shengyan Pharmaceutical Technology) 相关的药物交易

登录后查看更多信息