Labanca Caterina, Martino Enrica Antonia, Vigna Ernesto, Bruzzese Antonella, Mendicino Francesco, Lucia Eugenio, Olivito Virginia, Puccio Noemi, Neri Antonino, Morabito Fortunato, Gentile Massimo
Hematology Unit, Azienda Ospedaliera Annunziata, Cosenza, Italy.
Laboratorio di Ricerca Traslazionale Azienda USL-IRCSS Reggio Emilia, Emilia-Romagna, Italy.
Eur J Haematol. 2025 Mar;114(3):386-399. doi: 10.1111/ejh.14353. Epub 2024 Nov 27.
Relapsed and refractory multiple myeloma (RRMM) remains a challenging condition despite advances in immunotherapies. Novel bispecific antibodies (BsAbs), including talquetamab, have shown promising efficacy in heavily pretreated patients, even those with triple- and penta-refractory disease. Talquetamab, recently approved by the FDA and EMA, is indicated for patients who have progressed after at least three or four prior lines of therapy (LOTs). Administered following a step-up dosing phase to manage cytokine release syndrome (CRS), talquetamab demonstrated a high overall response rate (ORR) of approximately 70%, including in patients previously treated with T-cell redirecting therapies. Its safety profile is consistent with other BsAbs, with hematologic adverse events such as anemia and neutropenia commonly reported, alongside unique on-target off-tumor toxicities like dysgeusia and skin-related events. Infections were less frequent compared to other BsAbs. The optimal sequencing of talquetamab and other therapies, including CAR-T cell treatments, remains an area of active research, as resistance to anti-BCMA therapies presents ongoing clinical challenges. Current trials are exploring the use of talquetamab in combination therapies, as well as therapeutic strategies post-treating progression. The real-world data further support talquetamab's efficacy, making it a valuable addition to the RRMM treatment landscape.
尽管免疫疗法取得了进展，但复发难治性多发性骨髓瘤（RRMM）仍然是一个具有挑战性的病症。新型双特异性抗体（BsAbs），包括talquetamab，在经过大量预处理的患者中已显示出有前景的疗效，即使是那些患有三重难治和五重难治疾病的患者。Talquetamab最近获得了美国食品药品监督管理局（FDA）和欧洲药品管理局（EMA）的批准，适用于在至少经过三线或四线先前治疗方案（LOTs）后病情进展的患者。在逐步给药阶段后给药以控制细胞因子释放综合征（CRS），talquetamab显示出约70%的高总体缓解率（ORR），包括在先前接受过T细胞重定向疗法治疗的患者中。其安全性与其他BsAbs一致，常见报告有血液学不良事件，如贫血和中性粒细胞减少，以及独特的靶上非肿瘤毒性，如味觉障碍和皮肤相关事件。与其他BsAbs相比，感染的发生率较低。Talquetamab与其他疗法，包括CAR-T细胞治疗的最佳序贯治疗，仍然是一个活跃的研究领域，因为对抗BCMA疗法的耐药性带来了持续的临床挑战。当前的试验正在探索talquetamab在联合疗法中的应用，以及治疗进展后的治疗策略。真实世界的数据进一步支持了talquetamab的疗效，使其成为RRMM治疗领域的一个有价值的补充。
