Impact of extramedullary plasmacytoma on outcomes in patients with relapsed refractory multiple myeloma treated with talquetamab: U.S. Myeloma Immunotherapy Consortium

Talquetamab, a GPRC5D-targeting bispecific antibody, shows promising activity in relapsed-refractory multiple myeloma. However, real-world outcomes in patients with extramedullary disease (EMD) remain poorly described. We studied 360 patients treated with talquetamab at 15 U.S. centers by Dec 2024. Soft tissue plasmacytomas (STP) were classified as EMD (not contiguous with bone) or paraskeletal disease (PSD; contiguous with bone). If both were present, patients were assigned to the EMD category. Of those, 97 (27%) had EMD, 22 (6%) had PSD, and 241 (67%) had No-STP. Median follow-up was 12.8 months. Overall response rates were 68% in EMD, 63% in PSD, and 65% in No-STP (p = 0.8). Median progression-free survival was 4.3, 4.5, and 7.8 months, respectively (p = 0.009), and median overall survival was 10.3 months, 13.0 months, and not reached (p = 0.070). These findings demonstrate that EMD and PSD are associated with preserved response rates but shorter PFS and OS with talquetamab. While systemic markers of tumor burden and inflammation—particularly lactate dehydrogenase (LDH) and ferritin—emerged as independent predictors of inferior PFS, elevated LDH also retained independent prognostic significance for OS. While EMD was associated with shorter PFS and OS on univariate analysis, it did not retain independent prognostic significance on multivariable analysis, suggesting that inferior outcomes are driven by aggressive disease biology rather than by lesion anatomy alone. These findings are hypothesis-generating and require prospective validation. Talquetamab retains clinical utility in this high-risk population with EMD, though outcomes are suboptimal with a need for further refinement of treatment approaches.

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Journal
Blood Cancer Journal
Published
2026-07-27
DOI
https://doi.org/10.1038/s41408-026-01565-0
Primary Topic
Multiple Myeloma Research and Treatments
Type
article
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0.00

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article

Impact of extramedullary plasmacytoma on outcomes in patients with relapsed refractory multiple myeloma treated with talquetamab: U.S. Myeloma Immunotherapy Consortium

Jack Khouri, Mahmoud Gaballa, Luciano J. Costa, Adeel Khan et al.
Blood Cancer Journal
Multiple Myeloma Research and Treatments
article

Impact of extramedullary plasmacytoma on outcomes in patients with relapsed refractory multiple myeloma treated with talquetamab: U.S. Myeloma Immunotherapy Consortium

Jack Khouri, Mahmoud Gaballa, Luciano J. Costa, Adeel Khan, Faiz Anwer, Aimaz Afrough, Eli Zolotov, Surbhi Sidana, Rahul Kumar Banerjee, Danai Dima, Shonali Midha, Hitomi Hosoya, Shaji Kunnathu Kumar, Jeries Kort, Andrew J. Portuguese, Lindsay Fogel, Shahzad Raza, Lekha Mikkilineni, Cindy Varga, Larry D. Anderson, Utkarsh Goel, Shebli Atrash, Samer Al Hadidi, Omar Alexis Castaneda Puglianini, Doris K. Hansen, Murali Janakiram, Noa Biran, Hamza Hassan, Omar Nadeem, Douglas W. Sborov, Krina K. Patel, Kelley Julian, Oren Pasvolsky, Saurabh Zanwar, Megan M. Herr, Masooma Rana, Christopher J. Ferreri, Susan Bal, Brandon Jamaal Blue, James A. Davis, Yi Lin, Laura Joiner, Ariel Grajales‐Cruz, Frederick L. Locke, Ciara Freeman, Hossam M. Ali, Peter M. Voorhees, Scott Goldsmith, Rachid Baz, Aishwarya Sannareddy, Kimberly Green, Leyla Shune, Andre De Menezes Silva Corraes, Raffaela Cassano Cassano, Christina Ye
article en

Abstract

Talquetamab, a GPRC5D-targeting bispecific antibody, shows promising activity in relapsed-refractory multiple myeloma. However, real-world outcomes in patients with extramedullary disease (EMD) remain poorly described. We studied 360 patients treated with talquetamab at 15 U.S. centers by Dec 2024. Soft tissue plasmacytomas (STP) were classified as EMD (not contiguous with bone) or paraskeletal disease (PSD; contiguous with bone). If both were present, patients were assigned to the EMD category. Of those, 97 (27%) had EMD, 22 (6%) had PSD, and 241 (67%) had No-STP. Median follow-up was 12.8 months. Overall response rates were 68% in EMD, 63% in PSD, and 65% in No-STP (p = 0.8). Median progression-free survival was 4.3, 4.5, and 7.8 months, respectively (p = 0.009), and median overall survival was 10.3 months, 13.0 months, and not reached (p = 0.070). These findings demonstrate that EMD and PSD are associated with preserved response rates but shorter PFS and OS with talquetamab. While systemic markers of tumor burden and inflammation—particularly lactate dehydrogenase (LDH) and ferritin—emerged as independent predictors of inferior PFS, elevated LDH also retained independent prognostic significance for OS. While EMD was associated with shorter PFS and OS on univariate analysis, it did not retain independent prognostic significance on multivariable analysis, suggesting that inferior outcomes are driven by aggressive disease biology rather than by lesion anatomy alone. These findings are hypothesis-generating and require prospective validation. Talquetamab retains clinical utility in this high-risk population with EMD, though outcomes are suboptimal with a need for further refinement of treatment approaches.

Blood Cancer Journal
Roswell Park Comprehensive Cancer Center (US), Cleveland Clinic (US), The University of Texas MD Anderson Cancer Center (US), Medical University of South Carolina (US), University of Utah (US), Huntsman Cancer Institute (US), Moffitt Cancer Center (US), University of Alabama at Birmingham (US), Fred Hutch Cancer Center (US), Southwestern Medical Center (US), Levine Cancer Institute (US), City of Hope (US), Dana-Farber Cancer Institute (US), Mayo Clinic in Arizona (US), University of Kansas Medical Center (US), Hackensack Meridian Health (US), The University of Texas Southwestern Medical Center (US), Stanford University (US)
Amgen, Bristol-Myers Squibb, Pfizer, AstraZeneca, GlaxoSmithKline, Sanofi, Leukemia and Lymphoma Society, Gilead Sciences, Celgene, Regeneron Pharmaceuticals, Society for Immunotherapy of Cancer, Prothena, bluebird bio, Adaptive Biotechnologies, BeiGene, Incyte, Aptitude Health, Genentech, Kite Pharma, Legend Biotech, National Cancer Institute
Good health and well-being
Openalex Percentile: Top 9%
Multiple Myeloma Research and Treatments
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