PMID- 38402374 OWN - NLM STAT- MEDLINE DCOM- 20240325 LR - 20240518 IS - 1865-8652 (Electronic) IS - 0741-238X (Print) IS - 0741-238X (Linking) VI - 41 IP - 4 DP - 2024 Apr TI - Comparative Efficacy of Talquetamab vs. Current Treatments in the LocoMMotion and MoMMent Studies in Patients with Triple-Class-Exposed Relapsed/Refractory Multiple Myeloma. PG - 1576-1593 LID - 10.1007/s12325-024-02797-x [doi] AB - INTRODUCTION: Talquetamab, a bispecific antibody targeting GPRC5D x CD3, is approved for the treatment of patients with triple-class -exposed (TCE) relapsed/refractory multiple myeloma (RRMM) on the basis of the results from the phase I/II MonumenTAL-1 trial. The relative effectiveness of talquetamab vs. real-world physician's choice of therapy (RWPC) was assessed using adjusted comparisons. METHODS: An external control arm for MonumenTAL-1 (subcutaneously administered talquetamab 0.4 mg/kg weekly [QW] and 0.8 mg/kg every other week [Q2W]) was created from two observational real-world studies: LocoMMotion and MoMMent. Imbalances in baseline covariates were adjusted using inverse probability weighting. The relative effectiveness of talquetamab vs. RWPC was estimated for overall response rate (ORR), >/= very good partial response (VGPR), and >/= complete response (CR); odds ratios and relative response ratios (RRs) were derived from weighted logistic regression. Hazard ratios (HRs) for duration of response (DOR), progression-free survival (PFS), time to next treatment (TTNT), and overall survival (OS) were estimated using a weighted Cox proportional hazards model. RESULTS: After reweighting, baseline characteristics were balanced across cohorts. In adjusted comparisons, patients treated with talquetamab QW (n = 143) had significantly improved outcomes vs. RWPC; RRs were ORR 2.67, p < 0.0001; >/= VGPR 4.70, p < 0.0001; >/= CR 78.05, p = 0.0002; and HRs were PFS 0.52, p < 0.0001; TTNT 0.48, p < 0.0001; OS 0.36, p < 0.0001. Patients treated with talquetamab Q2W (n = 145) also had significantly improved outcomes vs. RWPC; RRs were ORR 2.62, p < 0.0001; >/= VGPR 5.04, p < 0.0001; >/= CR 101.14, p = 0.0002; and HRs were PFS 0.40, p < 0.0001; TTNT 0.39, p < 0.0001; OS 0.37, p < 0.0001. CONCLUSION: Effectiveness of talquetamab for both schedules was significantly better than RWPC for ORR, >/= VGPR, >/= CR, PFS, OS, and TTNT, highlighting its clinical benefit for patients with TCE RRMM. TRIAL REGISTRATION: MonumenTAL-1, ClinicalTrials.gov identifier NCT03399799/NCT04634552; LocoMMotion, ClinicalTrials.gov identifier NCT04035226; MoMMent, ClinicalTrials.gov identifier NCT05160584. CI - (c) 2024. The Author(s). FAU - Einsele, Hermann AU - Einsele H AD - Medizinische Klinik und Poliklinik II, Universitatsklinikum Wurzburg, Wurzburg, Germany. FAU - Moreau, Philippe AU - Moreau P AD - Hematology Clinic, University Hospital Hotel-Dieu, Nantes, France. FAU - Bahlis, Nizar AU - Bahlis N AD - Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, AB, Canada. FAU - Bhutani, Manisha AU - Bhutani M AD - Atrium Health Levine Cancer Institute/Wake Forest School of Medicine, Winston-Salem, NC, USA. FAU - Vincent, Laure AU - Vincent L AD - Departement d'hematologie Clinique, Centre Hospitalier Universitaire de Montpellier, Montpellier, France. FAU - Karlin, Lionel AU - Karlin L AD - Centre Hospitalier Lyon, Sud, France. FAU - Perrot, Aurore AU - Perrot A AD - Service d'Hematologie, Centre Hospitalier Universitaire de Toulouse, Toulouse, France. FAU - Goldschmidt, Hartmut AU - Goldschmidt H AD - Medizinische Klinik V, Universitatsklinikum Heidelberg and Nationales Centrum fur Tumorerkrankungen, Heidelberg, Germany. FAU - van de Donk, Niels W C J AU - van de Donk NWCJ AD - Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. FAU - Ocio, Enrique M AU - Ocio EM AD - Hospital Universitario Marques de Valdecilla (IDIVAL) Universidad de Cantabria, Santander, Spain. FAU - Martinez-Lopez, Joaquin AU - Martinez-Lopez J AD - Hematologia Hospital 12 de Octubre, Complutense University, CNIO, i+12, CIBERONC, Madrid, Spain. FAU - Rodriguez-Otero, Paula AU - Rodriguez-Otero P AD - CIMA, CIBERONC, IDISNA, Clinica Universidad de Navarra, Pamplona, Spain. FAU - Dytfeld, Dominik AU - Dytfeld D AD - Poznan University of Medical Sciences, Poznan, Poland. FAU - Diels, Joris AU - Diels J AD - Janssen Pharmaceutica NV, Beerse, Belgium. FAU - Strulev, Vadim AU - Strulev V AD - Janssen Pharmaceutica NV, Beerse, Belgium. FAU - Haddad, Imene AU - Haddad I AD - Janssen-Cilag, Issy-les-Moulineaux, France. FAU - Renaud, Thomas AU - Renaud T AD - Johnson & Johnson Innovative Medicine, Raritan, NJ, USA. FAU - Ammann, Eric AU - Ammann E AD - Janssen Global Services, Raritan, NJ, USA. FAU - Cabrieto, Jedelyn AU - Cabrieto J AD - Janssen Pharmaceutica NV, Beerse, Belgium. FAU - Perualila, Nolen AU - Perualila N AD - Janssen Pharmaceutica NV, Beerse, Belgium. FAU - Gan, Ryan AU - Gan R AD - Johnson & Johnson Innovative Medicine, Brisbane, CA, USA. FAU - Zhang, Youyi AU - Zhang Y AD - Johnson & Johnson Innovative Medicine, Raritan, NJ, USA. FAU - Parekh, Trilok AU - Parekh T AD - Johnson & Johnson Innovative Medicine, Bridgewater, NJ, USA. FAU - Albrecht, Claire AU - Albrecht C AD - Janssen-Cilag, Issy-les-Moulineaux, France. FAU - Weisel, Katja AU - Weisel K AD - University Medical Center Hamburg-Eppendorf, Hamburg, Germany. FAU - Mateos, Maria-Victoria AU - Mateos MV AD - University Hospital of Salamanca/IBSAL/CIC/CIBERONC, Paseo de San Vincente, 58-182, 37007, Salamanca, Spain. mvmateos@usal.es. LA - eng SI - ClinicalTrials.gov/NCT05160584 SI - ClinicalTrials.gov/NCT04035226 SI - ClinicalTrials.gov/NCT04634552 PT - Journal Article DEP - 20240224 PL - United States TA - Adv Ther JT - Advances in therapy JID - 8611864 MH - Humans MH - *Multiple Myeloma/drug therapy MH - Antineoplastic Combined Chemotherapy Protocols/therapeutic use PMC - PMC10960754 OTO - NOTNLM OT - LocoMMotion OT - MoMMent OT - MonumenTAL-1 OT - Talquetamab OT - Triple-class-exposed relapsed/refractory multiple myeloma COIS- Hermann Einsele has received honoraria from Amgen, BMS, EUSA Pharma, Genesis, GSK, Janssen, Novartis, Sanofi, and Takeda, travel expenses from Amgen, EUSA Pharma, and Takeda and research funding from Amgen, Genesis, GSK, Janssen, Sanofi, and Takeda. Philippe Moreau has served in a consulting or advisory role and received honoraria from AbbVie, Amgen, Celgene, GSK, Janssen, Oncopeptides, and Sanofi. Nizar Bahlis has a consulting or advisory role with AbbVie, Amgen, BMS, Forus, GSK, Janssen, Pfizer, Sanofi, and Takeda, received honoraria from AbbVie, Amgen, BMS, Forus, Janssen, and Sanofi, has been a member of the steering committee at AbbVie, GSK, and Janssen and has received research funding from Janssen and Pfizer. Manisha Bhutani has received funding from Adaptive Biotechnologies, Amgen, Bluebird Bio, Bristol Myers Squibb/Celgene, Celularity Inc., Cerecor, Janssen, Legend Biotech, MedImmune, and Takeda. Laure Vincent has received funding from Janssen, honoraria from BMS and Janssen, travel expenses from Amgen, BMS, GSK, Janssen, Sanofi, and Takeda, and has participated on an advisory board for BMS, Janssen, and Takeda. Lionel Karlin has served in a consulting or advisory role and received honoraria from Amgen, BMS/Celgene, GSK, Janssen, Sanofi, Stemline, and Takeda, has received travel expenses from Amgen, BMS/Celgene, Janssen, Sanofi, and Takeda, and has an immediate family member employed by Laoratoira Aguettant. Aurore Perrot has received honoraria or served a consulting role with AbbVie, Amgen, BMS, Janssen, Pfizer, Sanofi, and Takeda. Hartmut Goldschmidt has served in a consulting or advisory role for Adaptive Biotechnologies, Amgen, BMS, Celgene, Janssen-Cilag, Sanofi, and Takeda, received travel funding from Janssen-Cilag and Sanofi, honoraria from Amgen, BMS, Celgene, Chugai Pharma, GSK, Janssen-Cilag, Novartis, and Sanofi, research funding from Amgen, BMS, Celgene, Chugai Pharma Europe, Incyte, Janssen, Molecular Partners, MSD, Mundipharma, Novartis, and Takeda, and discloses other relationships with Amgen, Celgene/BMS, Chugai Pharma Europe, Janssen, and Sanofi. Niels WCJ van de Donk has received research support from Amgen, Bristol Myers Squibb, Celgene, Cellectis, Janssen Pharmaceuticals, and Novartis, and serves on advisory boards for AbbVie, Adaptive, Amgen, Bayer, Bristol Myers Squibb, Celgene, Janssen Pharmaceuticals, Novartis, Pfizer, Roche, Servier, and Takeda (all paid to their institution). Enrique M Ocio, Joaquin Martinez Lopez, Paula Rodriguez-Otero, Dominik Dytfeld, Joris Diels, Vadim Strulev, Imene Haddad, Thomas Renaud, Eric Ammann, Jedelyn Cabrieto, Nolen Perualila, Ryan Gan, Youyi Zhang, Trilok Parekh, and Claire Albrecht are employees of Janssen and may own stock in Johnson & Johnson/Janssen. Katja Weisel has served in a consulting or advisory role for Adaptive Biotechnologies, Amgen, BMS, Celgene, GSK, Janssen-Cilag, Karyopharm Therapeutics, Oncopeptides, Roche, Sanofi, and Takeda, received travel, accommodations, and/or expenses from Amgen, BMS, Celgene, GSK, Janssen-Cilag, and Takeda, honoraria from AbbVie, Adaptive Biotechnologies, Amgen, BMS, Celgene, GSK, Janssen-Cilag, Karyopharm Therapeutics, Novartis, Oncopeptides, Pfizer, Roche/Genentech, Sanofi, and Takeda, and research funding from Amgen, BMS, Celgene, GSK, Janssen-Cilag, and Sanofi. Maria-Victoria Mateos has served in a consulting or advisory role for AbbVie, Amgen, Celgene, GSK, Janssen-Cilag, Pfizer, Regeneron, Roche/Genentech, and Takeda, and received honoraria from AbbVie/Genentech, Amgen, Celgene, GSK, Janssen-Cilag, Sanofi, and Takeda. EDAT- 2024/02/25 00:42 MHDA- 2024/03/25 06:42 PMCR- 2024/02/24 CRDT- 2024/02/24 23:29 PHST- 2023/10/11 00:00 [received] PHST- 2024/01/19 00:00 [accepted] PHST- 2024/03/25 06:42 [medline] PHST- 2024/02/25 00:42 [pubmed] PHST- 2024/02/24 23:29 [entrez] PHST- 2024/02/24 00:00 [pmc-release] AID - 10.1007/s12325-024-02797-x [pii] AID - 2797 [pii] AID - 10.1007/s12325-024-02797-x [doi] PST - ppublish SO - Adv Ther. 2024 Apr;41(4):1576-1593. doi: 10.1007/s12325-024-02797-x. Epub 2024 Feb 24.