Talquetamab, a T-Cell–Redirecting GPRC5D Bispecific Antibody for Multiple Myeloma

Chari, Ajai; Minnema, Monique C.; Berdeja, Jesús G.; Oriol, Albert; Donk, Niels W.C.J. van de; Rodríguez‐Otero, Paula; Askari, Elham; Mateos, María‐Victoria; Costa, Luciano J.; Caers, Jo; Verona, Raluca; Girgis, Suzette; Yang, Shiyi; Goldsmith, Rachel B; Xiang, Yang; Pillarisetti, Kodandaram; Hilder, Brandi; Russell, J S; Goldberg, Jenna D.; Krishnan, Amrita

doi:10.1056/nejmoa2204591

Cited by 183 publications

(142 citation statements)

References 34 publications

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“…A phase 1 dose-finding study (MonumenTAL-1) of RRMM patients who had progressed with established therapies reported an ORR of 64–70% for 74 patients receiving either 405 μg/kg S/C weekly or 800 μg/kg S/C alternate-weekly, including patients who had received prior BCMA therapy. CRS occurred in 77–80% of patients and was grade 1–2 in the vast majority [ 84 ]. Talquetamab is being assessed in a variety of combinations in the RRMM setting (MonumenTAL-2, NCT05050097; MonumenTAL-3, NCT05455320; MonumenTAL-5, NCT05461209), and as a dual antigen-targeting approach combined with teclistamab in the RedirecTT-1 study (NCT04586426).…”

Section: Improving Antigen Availabilitymentioning

confidence: 99%

Bispecific Antibodies in Multiple Myeloma: Opportunities to Enhance Efficacy and Improve Safety

Swan

Murphy

Glavey

et al. 2023

Cancers

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Multiple myeloma (MM) is the second most common haematological neoplasm of adults in the Western world. Overall survival has doubled since the advent of proteosome inhibitors (PIs), immunomodulatory agents (IMiDs), and monoclonal antibodies. However, patients with adverse cytogenetics or high-risk disease as determined by the Revised International Staging System (R-ISS) continue to have poorer outcomes, and triple-refractory patients have a median survival of less than 1 year. Bispecific antibodies (BsAbs) commonly bind to a tumour epitope along with CD3 on T-cells, leading to T-cell activation and tumour cell killing. These treatments show great promise in MM patients, with the first agent, teclistamab, receiving regulatory approval in 2022. Their potential utility is hampered by the immunosuppressive tumour microenvironment (TME), a hallmark of MM, which may limit efficacy, and by undesirable adverse events, including cytokine release syndrome (CRS) and infections, some of which may be fatal. In this review, we first consider the means of enhancing the efficacy of BsAbs in MM. These include combining BsAbs with other drugs that ameliorate the effect of the immunosuppressive TME, improving target availability, the use of BsAbs directed against multiple target antigens, and the optimal time in the treatment pathway to employ BsAbs. We then discuss methods to improve safety, focusing on reducing infection rates associated with treatment-induced hypogammaglobulinaemia, and decreasing the frequency and severity of CRS. BsAbs offer a highly-active therapeutic option in MM. Improving the efficacy and safety profiles of these agents may enable more patients to benefit from these novel therapies and improve outcomes for patients with high-risk disease.

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Section: Improving Antigen Availabilitymentioning

confidence: 99%

Bispecific Antibodies in Multiple Myeloma: Opportunities to Enhance Efficacy and Improve Safety

Swan

Murphy

Glavey

et al. 2023

Cancers

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“…19,20 Moreover, other drugs/regimens with alternative mechanism of action are not available in Italy. [21][22][23][24][25][26] F I G U R E 3 Refractoriness after LOT-1, LOT-2 and LOT-3 with secular trends. [Colour figure can be viewed at wileyonlinelibrary.com] Moving to LOT-4, where 62.5% of patients in our most recent cohort are triple refractory, the matter gets even more challenging.…”

Section: Line Of Therapymentioning

confidence: 99%

Real‐world assessment of treatment patterns and outcomes in patients with relapsed‐refractory multiple myeloma in an Italian haematological tertiary care centre

et al. 2023

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Multiple myeloma (MM) is a very complex and heterogeneous haematological disease that in Italy is diagnosed in over 5000 people every year. 1 Natural history of most MM patients is to receive many lines of therapy (LOTs) until their disease becomes refractory and incurable. 2 Nevertheless, several cross-sectional real-life studies 3-5 found a high rate of patients not achieving subsequent LOTs and an increasing worsening of survival outcomes line by line. However, the cross-sectional studies, by their very nature, take into account neither the changes regarding therapeutic approaches occurring over time nor the therapeutic regimens licensed in the different places.Really, in the last decade novel drugs as proteasome inhibitors (PIs), immunomodulatory agents (IMIDs) and monoclonal antibodies (mAbs) have been licensed for using in the early relapsed/refractory multiple myeloma (RRMM), moving then in the newly diagnosed (NDMM) setting as continuous or maintenance therapy, 6,7 increasing doubleand triple-refractory patients at early relapse. These patients may lack suitable treatment options in a not so distant future. Currently, as demonstrated by the real-life MAMMOTH 8 and LocoMMotion 9 studies, there is no standard of care

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“…The phase I MonumenTAL-1 trial assessed talquetamab monotherapy in 232 heavily pretreated patients (median of 6 prior lines of therapies); 79% had triple-class-refractory disease, 30% penta-drug-refractory disease and 87% disease refractory to the last line of therapy. After a median follow up of 11.7 months (for patients who received the 405-μg dose level) and 4.2 months (for patients who received the 800-μg dose level), ORR was 70% and 64%, respectively, with median duration of response being 10.2 months and 7.8 months, respectively [ 160 , 161 , 162 ].…”

Section: Available Therapeutic Modalitiesmentioning

confidence: 99%

Management of Relapsed–Refractory Multiple Myeloma in the Era of Advanced Therapies: Evidence-Based Recommendations for Routine Clinical Practice

Dima

Ullah

Mazzoni

et al. 2023

Cancers

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Multiple myeloma (MM) is the second most common hematologic malignancy in adults worldwide. Over the past few years, major therapeutic advances have improved progression-free and overall survival, as well as quality of life. Despite this recent progress, MM remains incurable in the vast majority of cases. Patients eventually relapse and become refractory to multiple drug classes, making long-term management challenging. In this review, we will focus on the treatment paradigm of relapsed/refractory MM (RRMM) in the era of advanced therapies emphasizing the available novel modalities that have recently been incorporated into routine practice, such as chimeric antigen receptor T-cell therapy, bispecific antibodies, and other promising approaches. We will also discuss major factors that influence the selection of appropriate drug combinations or cellular therapies, such as relapse characteristics, and other disease and patient related parameters. Our goal is to provide insight into the currently available and experimental therapies for RRMM in an effort to guide the therapeutic decision-making process.

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Talquetamab, a T-Cell–Redirecting GPRC5D Bispecific Antibody for Multiple Myeloma

Cited by 183 publications

References 34 publications

Bispecific Antibodies in Multiple Myeloma: Opportunities to Enhance Efficacy and Improve Safety

Bispecific Antibodies in Multiple Myeloma: Opportunities to Enhance Efficacy and Improve Safety

Real‐world assessment of treatment patterns and outcomes in patients with relapsed‐refractory multiple myeloma in an Italian haematological tertiary care centre

Management of Relapsed–Refractory Multiple Myeloma in the Era of Advanced Therapies: Evidence-Based Recommendations for Routine Clinical Practice

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