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      Real-world experience of patients with multiple myeloma receiving ide-cel after a prior BCMA-targeted therapy

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      1 , 1 , 2 , 3 , 3 , 4 , 4 , 5 , 5 , 6 , 6 , 7 , 7 , 8 , 8 , 8 , 9 , 2 , 1 , 10 , 11 , 12 , 13 , 10 , 10 , 14 , 10 , 1 , , 10
      Blood Cancer Journal
      Nature Publishing Group UK
      Myeloma, Myeloma, Cancer immunotherapy, Cancer therapeutic resistance

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          Abstract

          Most patients with multiple myeloma experience disease relapse after treatment with a B-cell maturation antigen-targeted therapy (BCMA-TT), and data describing outcomes for patients treated with sequential BCMA-TT are limited. We analyzed clinical outcomes for patients infused with standard-of-care idecabtagene vicleucel, an anti-BCMA chimeric antigen receptor (CAR) T-cell therapy, at 11 US medical centers. A total of 50 patients with prior BCMA-TT exposure (38 antibody-drug conjugate, 7 bispecific, 5 CAR T) and 153 patients with no prior BCMA-TT were infused with ide-cel, with a median follow-up duration of 4.5 and 6.0 months, respectively. Safety outcomes between cohorts were comparable. The prior BCMA-TT cohort had a lower overall response rate (74% versus 88%; p = 0.021), median duration of response (7.4 versus 9.6 months; p = 0.03), and median progression-free survival (3.2 months versus 9.0 months; p = 0.0002) compared to the cohort without prior BCMA-TT. All five patients who received a prior anti-BCMA CAR T responded to ide-cel, and survival outcomes were best for this subgroup. In conclusion, treatment with ide-cel yielded meaningful clinical responses in real-world patients exposed to a prior BCMA-TT, though response rates and durability were suboptimal compared to those not treated with a prior BCMA-TT.

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          ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells

          Chimeric antigen receptor (CAR) T cell therapy is rapidly emerging as one of the most promising therapies for hematologic malignancies. Two CAR T products were recently approved in the United States and Europe for the treatment ofpatients up to age 25years with relapsed or refractory B cell acute lymphoblastic leukemia and/or adults with large B cell lymphoma. Many more CAR T products, as well as other immunotherapies, including various immune cell- and bi-specific antibody-based approaches that function by activation of immune effector cells, are in clinical development for both hematologic and solid tumor malignancies. These therapies are associated with unique toxicities of cytokine release syndrome (CRS) and neurologic toxicity. The assessment and grading of these toxicities vary considerably across clinical trials and across institutions, making it difficult to compare the safety of different products and hindering the ability to develop optimal strategies for management of these toxicities. Moreover, some aspects of these grading systems can be challenging to implement across centers. Therefore, in an effort to harmonize the definitions and grading systems for CRS and neurotoxicity, experts from all aspects of the field met on June 20 and 21, 2018, at a meeting supported by the American Society for Transplantation and Cellular Therapy (ASTCT; formerly American Society for Blood and Marrow Transplantation, ASBMT) in Arlington, VA. Here we report the consensus recommendations of that group and propose new definitions and grading for CRS and neurotoxicity that are objective, easy to apply, and ultimately more accurately categorize the severity of these toxicities. The goal is to provide a uniform consensus grading system for CRS and neurotoxicity associated with immune effector cell therapies, for use across clinical trials and in the postapproval clinical setting.
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            Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma

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              International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma.

              Treatment of multiple myeloma has substantially changed over the past decade with the introduction of several classes of new effective drugs that have greatly improved the rates and depth of response. Response criteria in multiple myeloma were developed to use serum and urine assessment of monoclonal proteins and bone marrow assessment (which is relatively insensitive). Given the high rates of complete response seen in patients with multiple myeloma with new treatment approaches, new response categories need to be defined that can identify responses that are deeper than those conventionally defined as complete response. Recent attempts have focused on the identification of residual tumour cells in the bone marrow using flow cytometry or gene sequencing. Furthermore, sensitive imaging techniques can be used to detect the presence of residual disease outside of the bone marrow. Combining these new methods, the International Myeloma Working Group has defined new response categories of minimal residual disease negativity, with or without imaging-based absence of extramedullary disease, to allow uniform reporting within and outside clinical trials. In this Review, we clarify several aspects of disease response assessment, along with endpoints for clinical trials, and highlight future directions for disease response assessments.
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                Author and article information

                Contributors
                KPatel1@mdanderson.org
                Journal
                Blood Cancer J
                Blood Cancer J
                Blood Cancer Journal
                Nature Publishing Group UK (London )
                2044-5385
                9 August 2023
                9 August 2023
                December 2023
                : 13
                : 1
                : 117
                Affiliations
                [1 ]GRID grid.240145.6, ISNI 0000 0001 2291 4776, The University of Texas MD Anderson Cancer Center, ; Houston, TX USA
                [2 ]GRID grid.259828.c, ISNI 0000 0001 2189 3475, Medical University of South Carolina, ; Charleston, SC USA
                [3 ]GRID grid.412016.0, ISNI 0000 0001 2177 6375, The University of Kansas Medical Center, ; Kansas City, KS USA
                [4 ]GRID grid.479969.c, ISNI 0000 0004 0422 3447, The University of Utah Huntsman Cancer Institute, ; Salt Lake City, UT USA
                [5 ]GRID grid.516103.0, ISNI 0000 0004 0376 1227, University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, ; Baltimore, MD USA
                [6 ]GRID grid.468189.a, Levine Cancer Institute, ; Charlotte, NC USA
                [7 ]GRID grid.239578.2, ISNI 0000 0001 0675 4725, Cleveland Clinic Taussig Cancer Center, ; Cleveland, OH USA
                [8 ]GRID grid.267313.2, ISNI 0000 0000 9482 7121, Myeloma, Waldenstrom’s, and Amyloidosis Program, Simmons Comprehensive Cancer Center, , UT Southwestern Medical Center, ; Dallas, TX USA
                [9 ]GRID grid.516131.1, ISNI 0000 0004 0369 1409, Virginia Commonwealth University Massey Cancer Center, ; Richmond, VA USA
                [10 ]GRID grid.468198.a, ISNI 0000 0000 9891 5233, H. Lee Moffitt Cancer Center and Research Institute, ; Tampa, FL USA
                [11 ]GRID grid.66875.3a, ISNI 0000 0004 0459 167X, Mayo Clinic, ; Rochester, MN USA
                [12 ]GRID grid.410425.6, ISNI 0000 0004 0421 8357, City of Hope, ; Duarte, CA USA
                [13 ]GRID grid.65499.37, ISNI 0000 0001 2106 9910, Dana-Farber Cancer Institute, ; Boston, MA USA
                [14 ]GRID grid.168010.e, ISNI 0000000419368956, Stanford University School of Medicine, ; Stanford, CA USA
                Author information
                http://orcid.org/0000-0003-2997-4856
                http://orcid.org/0000-0002-0539-4796
                http://orcid.org/0000-0003-0568-0781
                http://orcid.org/0000-0002-6531-9595
                http://orcid.org/0000-0001-7978-1652
                http://orcid.org/0000-0002-6620-8600
                http://orcid.org/0000-0002-1556-6416
                http://orcid.org/0000-0003-3288-7614
                http://orcid.org/0000-0002-8894-027X
                http://orcid.org/0000-0003-0423-5870
                Article
                886
                10.1038/s41408-023-00886-8
                10412575
                37558706
                b0dc8622-6806-484b-9f90-9e04069e6949
                © Springer Nature Limited 2023

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 4 May 2023
                : 26 June 2023
                : 21 July 2023
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                © Springer Nature Limited 2023

                Oncology & Radiotherapy
                myeloma,cancer immunotherapy,cancer therapeutic resistance
                Oncology & Radiotherapy
                myeloma, cancer immunotherapy, cancer therapeutic resistance

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