Abstract
Talquetamab is a first-in-class G protein–coupled receptor family C group 5 member D (GPRC5D) and CD3-targeting bispecific antibody with > 71% overall response in patients with relapsed or refractory multiple myeloma who have progressed on three other drug classes. GPRC5D is highly expressed on myeloma cells, along with some expression in normal hair follicles, skin, and tongue. Its unique expression on these normal tissues results in a distinct pattern of adverse events (AEs), as observed in the phase I/II MonumenTAL-1 trial. GPRC5D-related AEs included oral side effects (e.g., dysgeusia, dysphagia, xerostomia) and dermatologic toxicities (e.g., skin, nail). These AEs can be managed by dose modifications, emollients, and/or topical or oral corticosteroids. Cytokine release syndrome and immune effector cell−associated neurotoxicity syndrome were consistent with the T-cell redirection mechanism of talquetamab and can be managed consistent with other trials of T-cell redirection therapies. Infection rates were mostly grades 1 or 2, and grade ≥ 3 infection rates were lower than B-cell maturation antigen−targeting bispecific antibodies; infections were treated with anti-infective agents. Adverse events were manageable and led to few treatment discontinuations. This review reports on talquetamab safety in MonumenTAL-1, with an additional pharmacy focus on strategies related to drug dispensing and clinical management.
References
Berdeja, J. G., Madduri, D., Usmani, S. Z., Jakubowiak, A., Agha, M., Cohen, A. D.,...Lesokhin, A. (2021). Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): A phase 1b/2 open-label study. The Lancet, 398(10297), 314–324. https://doi.org/10.1016/S0140-6736(21)00933-8
CancerNetwork. (2024). Inpatient vs outpatient use of teclistamab in multiple myeloma. https://www.cancernetwork.com/view/inpatient-vs-outpatient-use-of-teclistamab-in-multiple-myeloma
Chari, A., Krishnan, A., Rasche, L., Ye, J. C., Garfall, A., Popat, R.,...van de Donk, N. W. C. J. (2024). Clinical management of patients with relapsed/refractory multiple myeloma treated with talquetamab. Clinical Lymphoma, Myeloma and Leukemia, 24(10), 665–693.E14. https://doi.org/10.1016/j.clml.2024.05.003
Chari, A., Minnema, M. C., Berdeja, J. G., Oriol, A., van de Donk, N. W. C. J., Rodríguez-Otero, P.,...Krishnan, A. (2022). Talquetamab, a T-cell–redirecting GPRC5D bispecific antibody for multiple myeloma. New England Journal of Medicine, 387(24), 2232–2244. https://doi.org/10.1056/NEJMoa2204591
Cohen, Y. C., Morillo, D., Gatt, M. E., Sebag, M., Kim, K., Min, C.-K.,...Magen, H. (2023). First results from the RedirecTT-1 study with teclistamab (tec) + talquetamab (tal) simultaneously targeting BCMA and GPRC5D in patients (pts) with relapsed/refractory multiple myeloma (RRMM). Journal of Clinical Oncology, 41(16 suppl), 8002. https://doi.org/10.1200/JCO.2023.41.16_suppl.8002
Dholaria, B. R., Weisel, K., Mateos, M.-V., Goldschmidt, H., Martin, T. G., Morillo, D.,...Chari, A. (2023). Talquetamab (tal) + daratumumab (dara) in patients (pts) with relapsed/refractory multiple myeloma (RRMM): Updated TRIMM-2 results. Journal of Clinical Oncology, 41(16 suppl), 8003. https://doi.org/10.1200/JCO.2023.41.16_suppl.8003
European Medicines Agency. (2024). Talquetamab summary of product characteristics. https://www.ema.europa.eu/en/documents/product-information/talvey-epar-product-information_en.pdf
Goldsmith, R., Cornax, I., Ma, J. Y., Yao, X., Peng, P., & Carreira, V. (2021). P-095: Normal human tissue expression of G-protein coupled receptor 5D (GPRC5D), a promising novel target for multiple myeloma, is restricted to plasma cells and hard keratinized tissues. Clinical Lymphoma Myeloma and Leukemia, 21(suppl 2), S91. https://doi.org/https://doi.org/10.1016/S2152-2650(21)02229-1
Inoue, S., Nambu, T., & Shimomura, T. (2004). The RAIG family member, GPRC5D, is associated with hard-keratinized structures. Journal of Investigative Dermatology, 122(3), 565–573. https://doi.org/10.1046/j.0022-202X.2004.12628.x
Institute for Safe Medication Practices. (2023). Potential for mix-ups between Talvey and Tecvayli. https://www.ismp.org/communityambulatory/medication-safety-alert-october-2023/ascension
International Agency for Research on Cancer & World Health Organization. (2022). Multiple myeloma. GLOBOCAN 2022. https://gco.iarc.who.int/media/globocan/factsheets/cancers/35-multiple-myeloma-fact-sheet.pdf
Janssen Biotech Inc. (2023a). Talquetamab (Talvey) package insert. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761342s000lbl.pdf
Janssen Biotech Inc. (2023b). TECVAYLI® and TALVEY™ Risk Evaluation and Mitigation Strategy (REMS). https://www.tec-talrems.com/#Main
Kodama, T., Kochi, Y., Nakai, W., Mizuno, H., Baba, T., Habu, K.,...Akashi, K. (2019). Anti-GPRC5D/CD3 bispecific T-cell-redirecting antibody for the treatment of multiple myeloma. Molecular Cancer Therapeutics, 18(9), 1555–1564. https://doi.org/10.1158/1535-7163.MCT-18-1216
Kumar, S. K., Dispenzieri, A., Lacy, M. Q., Gertz, M. A., Buadi, F. K., Pandey, S.,...Rajkumar, S. V. (2014). Continued improvement in survival in multiple myeloma: Changes in early mortality and outcomes in older patients. Leukemia, 28(5), 1122–1128. https://doi.org/10.1038/leu.2013.313
Lancman, G., Parsa, K., Kotlarz, K., Avery, L., Lurie, A., Lieberman-Cribbin, A.,...Chari, A. (2023). IVIg use associated with ten-fold reduction of serious infections in multiple myeloma patients treated with anti-BCMA bispecific antibodies. Blood Cancer Discovery, 4(6), 440–451. https://doi.org/10.1158/2643-3230.BCD-23-0049
Lee, D. W., Santomasso, B. D., Locke, F. L., Ghobadi, A., Turtle, C. J., Brudno, J. N.,...Neelapu, S. S. (2019). ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. Biology of Blood and Marrow Transplantation, 25(4), 625–638. https://doi.org/10.1016/j.bbmt.2018.12.758
Lesokhin, A. M., Tomasson, M. H., Arnulf, B., Bahlis, N. J., Miles Prince, H., Niesvizky, R.,...Mohty, M. (2023). Elranatamab in relapsed or refractory multiple myeloma: Phase 2 MagnetisMM-3 trial results. Nature Medicine, 29(9), 2259–2267. https://doi.org/10.1038/s41591-023-02528-9
Ludwig, H., & Kumar, S. (2023). Prevention of infections including vaccination strategies in multiple myeloma. American Journal of Hematology, 98(suppl 2), S46–S62. https://doi.org/10.1002/ajh.26766
Ma, X., Gong, J., Zhou, J., Yuan, D., Vishwamitra, D., Hilder, B. W.,...Ouellet, D. (2023). Efficacy, Safety, Pharmacokinetic, and Pharmacodynamic Support for Talquetamab QW and Q2W Dosing in Patients With Relapsed/Refractory Multiple Myeloma: Analyses From MonumenTAL-1. American College of Clinical Pharmacology Congress, September 10–12, 2023, Bellevue, WA.
Mackler, E., Segal, E. M., Muluneh, B., Jeffers, K., & Carmichael, J. (2019). 2018 Hematology/Oncology Pharmacist Association Best Practices for the Management of Oral Oncolytic Therapy: Pharmacy Practice Standard. Journal of Oncology Practice, 15(4), e346–e355. https://doi.org/10.1200/JOP.18.00581
Martin, T. G., Mateos, M. V., Nooka, A., Banerjee, A., Kobos, R., Pei, L.,...Rodriguez, C. (2023). Detailed overview of incidence and management of cytokine release syndrome observed with teclistamab in the MajesTEC-1 study of patients with relapsed/refractory multiple myeloma. Cancer, 129(13), 2035-2046. https://doi.org/10.1002/cncr.34756
Mateos, M.-V., Weisel, K., De Stefano, V., Goldschmidt, H., Delforge, M., Mohty, M.,...Moreau, P. (2022). LocoMMotion: a prospective, non-interventional, multinational study of real-life current standards of care in patients with relapsed and/or refractory multiple myeloma. Leukemia, 36(5), 1371–1376. https://doi.org/10.1038/s41375-022-01531-2
Moreau, P., Garfall, A. L., van de Donk, N. W. C. J., Nahi, H., San-Miguel, J. F., Oriol, A.,...Usmani, S. Z. (2022). Teclistamab in relapsed or refractory multiple myeloma. New England Journal of Medicine, 387(6), 495–505. https://doi.org/10.1056/NEJMoa2203478
Munshi, N. C., Anderson, L. D., Shah, N., Madduri, D., Berdeja, J., Lonial, S.,...San-Miguel, J. (2021). Idecabtagene vicleucel in relapsed and refractory multiple myeloma. New England Journal of Medicine, 384(8), 705–716. https://doi.org/10.1056/NEJMoa2024850
Narayan, N., Williams, B., Lipe, B., & De Benedetto, A. (2023). Onychomadesis and palmoplantar keratoderma associated with talquetamab therapy for relapsed and refractory multiple myeloma. JAAD Case Reports, 31, 66–68. https://doi.org/10.1016/j.jdcr.2022.11.013
National Cancer Institute. (2021). Common Terminology Criteria for Adverse Events (CTCAE). https://ctep.cancer.gov/protocoldevelopment/electronic_applications/ctc.htm
Nooka, A. K., Rodriguez, C., Mateos, M. V., Manier, S., Chastain, K., Banerjee, A.,...van de Donk, N. (2024). Incidence, timing, and management of infections in patients receiving teclistamab for the treatment of relapsed/refractory multiple myeloma in the MajesTEC-1 study. Cancer, 130(6), 886-900. https://doi.org/10.1002/cncr.35107
Padala, S. A., Barsouk, A., Barsouk, A., Rawla, P., Vakiti, A., Kolhe, R.,...Ajebo, G. H. (2021). Epidemiology, staging, and management of multiple myeloma. Medical Sciences, 9(1), 3. https://doi.org/10.3390/medsci9010003
Patel, S., Cenin, D., Corrigan, D., Hamilton, B. K., Kalaycio, M., Sobecks, R. M.,...Caimi, P. F. (2022). Siltuximab for first-line treatment of cytokine release syndrome: A response to the national shortage of tocilizumab. Blood, 140(suppl 1), 5073–5074. https://doi.org/10.1182/blood-2022-169809
Rajkumar, S. V. (2020). Multiple myeloma: 2020 update on diagnosis, risk-stratification and management. American Journal of Hematology, 95(5), 548–567. https://doi.org/10.1002/ajh.25791
Rodríguez-Otero, P., Schinke, C. D., Chari, A., Lipe, B., Lavi, N., Rasche, L.,...van de Donk, N. W. C. J. (2023). Analysis of infections and parameters of humoral immunity in patients (pts) with relapsed/refractory multiple myeloma (RRMM) treated with talquetamab (tal) monotherapy in MonumenTAL-1. Journal of Clinical Oncology, 41(16_suppl), 8020-8020. https://doi.org/10.1200/JCO.2023.41.16_suppl.8020
Rodriguez-Otero, P., Usmani, S., Cohen, A. D., van de Donk, N., Leleu, X., Gallego Perez-Larraya, J.,...International Myeloma Working, G. (2024). International Myeloma Working Group immunotherapy committee consensus guidelines and recommendations for optimal use of T-cell-engaging bispecific antibodies in multiple myeloma. Lancet Oncology, 25(5), e205-e216. https://doi.org/10.1016/S1470-2045(24)00043-3
Saltarella, I., Altamura, C., Solimando, A. G., D’Amore, S., Ria, R., Vacca, A.,...Frassanito, M. A. (2024). Immunoglobulin replacement therapy: Insights into multiple myeloma management. Cancers, 16(18). https://doi.org/10.3390/cancers16183190
Schinke, C. D., Touzeau, C., Minnema, M. C., Donk, N. W. C. J. v. d., Rodríguez-Otero, P., Mateos, M.-V.,...Chari, A. (2023). Pivotal phase 2 MonumenTAL-1 results of talquetamab (tal), a GPRC5DxCD3 bispecific antibody (BsAb), for relapsed/refractory multiple myeloma (RRMM). Journal of Clinical Oncology, 41(16 suppl), 8036. https://doi.org/10.1200/JCO.2023.41.16_suppl.8036
Smith, E. L., Harrington, K., Staehr, M., Masakayan, R., Jones, J., Long, T. J.,...Brentjens, R. J. (2019). GPRC5D is a target for the immunotherapy of multiple myeloma with rationally designed CAR T cells. Science Translational Medicine, 11(485). https://doi.org/10.1126/scitranslmed.aau7746
Tanenbaum, B., Miett, T., & Patel, S. A. (2023). The emerging therapeutic landscape of relapsed/refractory multiple myeloma. Annals of Hematology, 102(1), 1–11. https://doi.org/10.1007/s00277-022-05058-5
Trudel, S., Bahlis, N. J., Spencer, A., Kaedbey, R., Rodriguez Otero, P., Harrison, S. J.,...Mateos, M.-V. (2022). Pretreatment with tocilizumab prior to the CD3 bispecific cevostamab in patients with relapsed/refractory multiple myeloma (RRMM) showed a marked reduction in cytokine release syndrome incidence and severity. Blood, 140(Supplement 1), 1363-1365. https://doi.org/10.1182/blood-2022-159381
Usmani, S. Z., Garfall, A. L., van de Donk, N., Nahi, H., San-Miguel, J. F., Oriol, A.,...Krishnan, A. (2021). Teclistamab, a B-cell maturation antigen x CD3 bispecific antibody, in patients with relapsed or refractory multiple myeloma (MajesTEC-1): A multicentre, open-label, single-arm, phase 1 study. The Lancet, 398(10301), 665–674. https://doi.org/10.1016/S0140-6736(21)01338-6
van de Donk, N. W. C. J., Garfall, A. L., Benboubker, L., Uttervall, K., Groen, K., Rosiñol, L.,...Mateos, M.-V. (2023). Evaluation of prophylactic tocilizumab (toci) for the reduction of cytokine release syndrome (CRS) to inform the management of patients (pts) treated with teclistamab in MajesTEC-1. Journal of Clinical Oncology, 41(16_suppl), 8033-8033. https://doi.org/10.1200/JCO.2023.41.16_suppl.8033
Verkleij, C. P. M., Broekmans, M. E. C., van Duin, M., Frerichs, K. A., Kuiper, R., de Jonge, A. V.,...van de Donk, N. (2021). Preclinical activity and determinants of response of the GPRC5DxCD3 bispecific antibody talquetamab in multiple myeloma. Blood Advances, 5(8), 2196–2215. https://doi.org/10.1182/bloodadvances.2020003805
Willan, J., Eyre, T. A., Sharpley, F., Watson, C., King, A. J., & Ramasamy, K. (2016). Multiple myeloma in the very elderly patient: Challenges and solutions. Clinical Interventions in Aging, 11, 423-435. https://doi.org/10.2147/CIA.S89465
