Outcomes of patients with multiple myeloma refractory to CD38-targeted monoclonal antibody therapy.
Open accessAbstract
The introduction of CD38-targeting monoclonal antibodies (CD38 MoABs), daratumumab and isatuximab, has significantly impacted the management of patients with multiple myeloma (MM). Outcomes of patients with MM refractory to CD38 MoABs have not been described. We analyzed outcomes of 275 MM patients at 14 academic centers with disease refractory to CD38 MoABs. Median interval between MM diagnosis and refractoriness to CD38 MoAB (T 0) was 50.1 months. The median overall survival (OS) from T 0 for the entire cohort was 8.6 [95% C.I. 7.5-9.9] months, ranging from 11.2 months for patients not simultaneously refractory to an immunomodulatory (IMiD) agent and a proteasome inhibitor (PI) to 5.6 months for "penta-refractory" patients (refractory to CD38 MoAB, 2 PIs and 2 IMiDs). At least one subsequent treatment regimen was employed after T 0 in 249 (90%) patients. Overall response rate to first regimen after T 0 was 31% with median progression-free survival (PFS) and OS of 3.4 and 9.3 months, respectively. PFS was best achieved with combinations of carfilzomib and alkylator (median 5.7 months), and daratumumab and IMiD (median 4.5 months). Patients with MM refractory to CD38 MoAB have poor prognosis and this study provides benchmark for new therapies to be tested in this population.
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There is no standard of care for early triple-class-exposed relapsed and refractory multiple myeloma.
“Management of relapsed MM remains challenging; patients are becoming triple-class exposed (TCE) earlier in their treatment course, 4-8 with no standard of care for early TCE relapsed and refractory MM (R/RMM).”
From Ide-cel vs standard regimens in triple-class-exposed relapsed and refractory multiple myeloma: updated KarMMa-3 analyses. (2024) · cites this paper as [6]
The Discussion (page unavailable) describes limited treatment options and poor outcomes after progression on CD38-targeted therapy. It does not establish that there is no standard of care specifically for patients who become triple-class exposed early in their treatment course. (LLM, conf=0.80)
Experimental — accuracy not yet measuredIn patients with triple-class-exposed relapsed and refractory multiple myeloma, conventional therapies yield poor prognosis, with median progression-free survival of approximately 3 to 5 months and median overall survival of approximately 9 to 22 months.
“Prognosis is poor with conventional therapies, with a median progression-free survival (PFS) of ~3 to 5 months and a median overall survival (OS) of ~9 to 22 months in this patient population. 5-12”
From Ide-cel vs standard regimens in triple-class-exposed relapsed and refractory multiple myeloma: updated KarMMa-3 analyses. (2024) · cites this paper as [6]
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Cites
Harris, P. A., Taylor, R., Thielke, R., Payne, J., Gonzalez, N., & Conde, J. G. (2009) · Journal of Biomedical Informatics · doi:10.1016/j.jbi.2008.08.010 · Cited by 51,384 · see citing works
International uniform response criteria for multiple myeloma
Durie, B. G. M., Harousseau, J.-L., Miguel, J. S., Bladé, J., Barlogie, B., Anderson, K., Gertz, M., Dimopoulos, M., Westin, J., Sonneveld, P., et al. (2006) · Leukemia · doi:10.1038/sj.leu.2404284 · Cited by 2,632 · see citing works
Daratumumab, Bortezomib, and Dexamethasone for Multiple Myeloma
Palumbo, A., Chanan-Khan, A., Weisel, K., Nooka, A. K., Masszi, T., Beksac, M., Spicka, I., Hungria, V., Munder, M., Mateos, M. V., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1606038 · Cited by 1,522 · see citing works
Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma.
Dimopoulos, M. A., Oriol, A., Nahi, H., San-Miguel, J., Bahlis, N. J., Usmani, S. Z., Rabin, N., Orlowski, R. Z., Komarnicki, M., Suzuki, K., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1607751 · Cited by 1,445 · see citing works
Self-citationKumar, S. K., Dispenzieri, A. A., Lacy, M. Q., Gertz, M. A., Buadi, F. K., Pandey, S., Kapoor, P., Dingli, D., Hayman, S. R., Leung, N., et al. (2013) · Leukemia · doi:10.1038/leu.2013.313 · Cited by 1,368 · see citing works
Self-citationRajkumar, S. V., Harousseau, J.-L., Durie, B., Anderson, K. C., Dimopoulos, M., Kyle, R., Blade, J., Richardson, P., Orlowski, R., Siegel, D., et al. (2011) · Blood · doi:10.1182/blood-2010-10-299487 · Cited by 1,036 · see citing works
Daratumumab plus Bortezomib, Melphalan, and Prednisone for Untreated Myeloma
Mateos, M., Dimopoulos, M. A., Cavo, M., Suzuki, K., Jakubowiak, A. J., Knop, S. T., Doyen, C., Lúcio, P., Nagy, Z., Kaplan, P., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1714678 · Cited by 991 · see citing works
Lonial, S., Weiss, B. M., Usmani, S. Z., Singhal, S., Chari, A., Bahlis, N. J., Belch, A., Krishnan, A., Vescio, R. A., Mateos, M. V., et al. (2016) · The Lancet · doi:10.1016/s0140-6736(15)01120-4 · Cited by 854 · see citing works
Self-citationMultiple Myeloma: Diagnosis and Treatment
Rajkumar, S. V., & Kumar, S. (2016) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2015.11.007 · Cited by 812 · see citing works
Self-citationCD38 antibodies in multiple myeloma: back to the future
van de Donk, N. W. C. J., Richardson, P. G. G., & Malavasi, F. (2017) · Blood · doi:10.1182/blood-2017-06-740944 · Cited by 495 · see citing works
Proteasome inhibitors in multiple myeloma: 10 years later
Moreau, P., Richardson, P. G. G., Cavo, M., Orlowski, R. Z., Miguel, J. F. S., Palumbo, A. P., & Harousseau, J. (2012) · Blood · doi:10.1182/blood-2012-04-403733 · Cited by 491 · see citing works
Daratumumab plus pomalidomide and dexamethasone in relapsed and/or refractory multiple myeloma
Chari, A., Suvannasankha, A., Fay, J. W., Arnulf, B., Kaufman, J. L., Ifthikharuddin, J. J., Weiss, B. M., Krishnan, A. Y., Lentzsch, S., Comenzo, R. L., et al. (2017) · Blood · doi:10.1182/blood-2017-05-785246 · Cited by 444 · see citing works
Kumar, S. K., Dimopoulos, M. A., Kastritis, E., Terpos, E., Nahi, H., Goldschmidt, H., Hillengass, J., Leleu, X., Beksac, M., Alsina, M., et al. (2017) · Leukemia · doi:10.1038/leu.2017.138 · Cited by 351 · see citing works
Self-citationTrudel, S., Lendvai, N. K., Popat, R., Voorhees, P. M., Reeves, B., Libby, E. N., Richardson, P. G. G., Anderson, L. D., Sutherland, H. J., Yong, K., et al. (2018) · The Lancet Oncology · doi:10.1016/s1470-2045(18)30576-x · Cited by 251 · see citing works
Martin, T. G., Baz, R., Benson, D. M., Lendvai, N. K., Wolf, J. L., Münster, P. N., Lesokhin, A. M., Wack, C., Charpentier, E., Campana, F., et al. (2017) · Blood · doi:10.1182/blood-2016-09-740787 · Cited by 166 · see citing works
Self-citationGenome-wide minor histocompatibility matching as related to the risk of graft-versus-host disease
Martin, P. J., Levine, D., Storer, B. E., Warren, E. H., Zheng, X., Nelson, S. C., Smith, A. G., Mortensen, B. K., & Hansen, J. A. (2016) · Blood · doi:10.1182/blood-2016-09-737700 · Cited by 116 · see citing works
Nooka, A. K., Joseph, N. S., Kaufman, J. L., Heffner, L. T., Gupta, V. A., Gleason, C. L., Boise, L., & Lonial, S. (2019) · Cancer · doi:10.1002/cncr.32178 · Cited by 91 · see citing works
How I treat myeloma with new agents
Moreau, P. (2017) · Blood · doi:10.1182/blood-2017-05-743203 · Cited by 81 · see citing works
Raje, N. S., Berdeja, J. G., Lin, Y., Munshi, N. C., Siegel, D. S. D., Liedtke, M., Jagannath, S., Madduri, D., Rosenblatt, J. M., Maus, M. V., et al. (2018) · Journal of Clinical Oncology · doi:10.1200/jco.2018.36.15_suppl.8007 · Cited by 59 · see citing works
Self-citationTopp, M. S., Duell, J., Zugmaier, G., Attal, M., Moreau, P., Langer, C., Kroenke, J., Facon, T., Einsele, H., & Munzert, G. (2018) · Blood · doi:10.1182/blood-2018-99-109769 · Cited by 55 · see citing works
Facon, T., Kumar, S. K., Plesner, T., Orlowski, R. Z., Moreau, P., Bahlis, N., Basu, S., Nahi, H., Hulin, C., Quach, H., et al. (2018) · Blood · doi:10.1182/blood-2018-120737 · Cited by 50 · see citing works
Self-citationRichter, J. R., Martin, T. G., Vij, R., Cole, C. E., Atanackovic, D., Zonder, J. A., Kaufman, J. L., Mikhael, J. R., Bensinger, W., Dimopoulos, M. A., et al. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2016.34.15_suppl.8005 · Cited by 36 · see citing works
Self-citationPhase Ib Study of Isatuximab and Carfilzomib in Relapse and Refractory Multiple Myeloma
Martin, T. G., Mannis, G. N., Chari, A., Münster, P. N., Campana, F., Hui, A., & Wolf, J. L. (2016) · Blood · doi:10.1182/blood.v128.22.2111.2111 · Cited by 28 · see citing works
Nooka, A. K., Joseph, N. S., Boise, L. H., Gleason, C. L., Kaufman, J. L., & Lonial, S. (2016) · Blood · doi:10.1182/blood.v128.22.492.492 · Cited by 27 · see citing works
Kumar, S. K., Kapoor, P., LaPlant, B. R., et al. (2018) · Blood · doi:10.1182/blood-2018-99-111065 · Cited by 12 · see citing works
Self-citationMISTRG extends PDX modeling to favorable AMLs
Wunderlich, M., & Mulloy, J. C. (2016) · Blood · doi:10.1182/blood-2016-09-738757 · Cited by 11 · see citing works
Mikhael, J. R., Richardson, P. G. G., Usmani, S. Z., et al. (2018) · Journal of Clinical Oncology · doi:10.1200/jco.2018.36.15_suppl.8038 · Cited by 5 · see citing works
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- [19]Chari A, Suvannasankha A, Fay JW, Arnulf B, Kaufman JL, Ifthikharuddin JJ, Daratumumab plus pomalidomide and dexamethasone in relapsed and/or refractory multiple myeloma. Blood 2017; 130: 974– 981. 28637662 PMC5570682
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Munshi, N. C., Anderson, L. D., Shah, N., Madduri, D., Berdeja, J., Lonial, S., Raje, N., Lin, Y., Siegel, D., Oriol, A., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2024850 · Cited by 2,560 · see citing works
Berdeja, J. G., Madduri, D., Usmani, S. Z., Jakubowiak, A., Agha, M., Cohen, A. D., Stewart, A. K., Hari, P., Htut, M., Lesokhin, A., et al. (2021) · The Lancet · doi:10.1016/s0140-6736(21)00933-8 · Cited by 1,756 · see citing works
Self-citationLonial, S., Lee, H. C., Badros, A., Trudel, S., Nooka, A. K., Chari, A., Abdallah, A.-O., Callander, N., Lendvai, N., Sborov, D., et al. (2020) · The Lancet Oncology · doi:10.1016/s1470-2045(19)30788-0 · Cited by 812 · see citing works
Self-citationIde-cel or Standard Regimens in Relapsed and Refractory Multiple Myeloma
Rodriguez-Otero, P., Ailawadhi, S., Arnulf, B., Patel, K., Cavo, M., Nooka, A. K., Manier, S., Callander, N., Costa, L. J., Vij, R., et al. (2023) · New England Journal of Medicine · doi:10.1056/nejmoa2213614 · Cited by 781 · see citing works
Self-citationMateos, M.-V., Weisel, K., De Stefano, V., Goldschmidt, H., Delforge, M., Mohty, M., Cavo, M., Vij, R., Lindsey-Hill, J., Dytfeld, D., et al. (2022) · Leukemia · doi:10.1038/s41375-022-01531-2 · Cited by 252 · see citing works
Self-citationRaje, N., Anderson, K., Einsele, H., Efebera, Y., Gay, F., Hammond, S. P., Lesokhin, A. M., Lonial, S., Ludwig, H., Moreau, P., et al. (2023) · Blood Cancer Journal · doi:10.1038/s41408-023-00879-7 · Cited by 209 · see citing works
Belantamab Mafodotin, Pomalidomide, and Dexamethasone in Multiple Myeloma
Dimopoulos, M. A., Beksac, M., Pour, L., Delimpasi, S., Vorobyev, V., Quach, H., Spicka, I., Radocha, J., Robak, P., Kim, K., et al. (2024) · New England Journal of Medicine · doi:10.1056/nejmoa2403407 · Cited by 189 · see citing works
Verkleij, C. P. M., Broekmans, M. E. C., van Duin, M., Frerichs, K. A., Kuiper, R., de Jonge, A. V., Kaiser, M., Morgan, G., Axel, A., Boominathan, R., et al. (2021) · Blood Advances · doi:10.1182/bloodadvances.2020003805 · Cited by 182 · see citing works
Lonial, S., Lee, H. C., Badros, A., Trudel, S., Nooka, A. K., Chari, A., Abdallah, A., Callander, N., Sborov, D., Suvannasankha, A., et al. (2021) · Cancer · doi:10.1002/cncr.33809 · Cited by 144 · see citing works
Self-citationTreatment options for triple-class refractory multiple myeloma.
Mikhael, J. (2020) · Clinical Lymphoma Myeloma and Leukemia · doi:10.1016/j.clml.2019.09.621 · Cited by 126 · see citing works
Dimopoulos, M. A., Dytfeld, D., Grosicki, S., Moreau, P., Takezako, N., Hori, M., Leleu, X., LeBlanc, R., Suzuki, K., Raab, M. S., et al. (2023) · Journal of Clinical Oncology · doi:10.1200/jco.21.02815 · Cited by 114 · see citing works
Ailawadhi, S., Arnulf, B., Patel, K., Cavo, M., Nooka, A. K., Manier, S., Callander, N., Costa, L. J., Vij, R., Bahlis, N. J., et al. (2024) · Blood · doi:10.1182/blood.2024024582 · Cited by 79 · see citing works
Self-citationDhanasiri, S., Hollier-Hann, G., Stothard, C., Dhanda, D. S., Davies, F. E., & Rodriguez-Otero, P. (2021) · Clinical Therapeutics · doi:10.1016/j.clinthera.2021.09.013 · Cited by 22 · see citing works
I-OPen: inferior outcomes of penta-refractory compared to penta-exposed multiple myeloma patients
Gill, S. K., Unawane, R., Wang, S., Ahn, J., Aleman, A., Siegel, D. S., Vesole, D. H., Parmar, H., Phull, P., & Biran, N. (2022) · Blood Cancer Journal · doi:10.1038/s41408-022-00733-2 · Cited by 16 · see citing works
- Authors
- Gandhi, U. H., Cornell, R. F., Lakshman, A., Gahvari, Z. J., McGehee, E., Jagosky, M. H., Gupta, R., Varnado, W., Fiala, M. A., Chhabra, S., Malek, E., Mansour, J., Paul, B., Barnstead, A., Kodali, S., Neppalli, A., Liedtke, M., Narayana, S., Godby, K. N., Kang, Y., Kansagra, A., Umyarova, E., Scott, E. C., Hari, P., Vij, R., Usmani, S. Z., Callander, N. S., Kumar, S. K., & Costa, L. J.
- Affiliations
- Vanderbilt University Medical Center (US)
- Mayo Clinic (US)
- University of Wisconsin–Madison (US)
- The University of Texas Southwestern Medical Center (US)
- Levine Cancer Institute (US)
- Stanford Cancer Institute (US)
- University of Alabama at Birmingham (US)
- Washington University in St. Louis (US)
- Medical College of Wisconsin (US)
- University Hospitals Cleveland Medical Center (US)
- Medical University of South Carolina (US)
- Duke University (US)
- Oregon Health & Science University (US)
- University of Vermont (US)
- Corresponding author
- Costa, Luciano J.
- ORCID
- Cornell, Robert F.
- Lakshman, Arjun
- McGehee, Elizabeth
- Jagosky, Megan H.
- Gupta, Ridhi
- Fiala, Mark A.
- Chhabra, Saurabh
- Malek, Ehsan
- Paul, Barry
- Liedtke, Michaela
- Kang, Yubin
- Kansagra, Ankit
- Umyarova, Elvira
- Scott, Emma C.
- Hari, Parameswaran
- Vij, Ravi
- Usmani, Saad Z.
- Callander, Natalie S.
- Kumar, Shaji K.
- Costa, Luciano J.
- Venue
- Leukemia
- Published
- 2019-03-11
- Volume
- 33
- Issue
- 9
- Pages
- 2266-2275
- ISSN
- 0887-6924 (ISSN-L)
- 1476-5551
- PMC
- PMC6820050
- OpenAlex
- W2921533600
- Cited by
- 616
- References
- 27
- Citations by year
- 2026: 35 · 2025: 79 · 2024: 109 · 2023: 115 · 2022: 106 · 2021: 110 · 2020: 55 · 2019: 3 · 2018: 1
- FWCI
- 48.35
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Leukemia (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Vanderbilt University Medical Center
- National Cancer Institute (P30CA091842)
- Topics
- Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
- Health Sciences › Medicine › Genetics › Chronic Lymphocytic Leukemia Research
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Keywords
- multiple myeloma, daratumumab, isatuximab, refractory disease, overall survival, progression-free survival, carfilzomib, immunomodulators, proteasome inhibitors, second-line therapy
- MeSH terms
- Antineoplastic Agents, Immunological, Progression-Free Survival, Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Antineoplastic Combined Chemotherapy Protocols, Female, Humans, Immunologic Factors, Immunotherapy, Male, Membrane Glycoproteins, Middle Aged, Multiple Myeloma, Cohort Studies, ADP-ribosyl Cyclase 1, Young Adult, Antibodies, Monoclonal, Humanized, Proteasome Inhibitors
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