Immune effector cell-associated enterocolitis following chimeric antigen receptor T-cell therapy in multiple myeloma DOI Creative Commons
Gliceida Galarza Fortuna, Rahul Banerjee, Constanza Savid-Frontera

et al.

Blood Cancer Journal, Journal Year: 2024, Volume and Issue: 14(1)

Published: Oct. 16, 2024

We report 14 cases of immune effector cell (IEC)-associated enterocolitis following chimeric antigen receptor T-cell (CAR-T) therapy in multiple myeloma, with a 1.2% incidence overall (0.2% for idecabtagene vicleucel and 2.2% ciltacabtagene autoleucel). Patients developed acute-onset symptoms (typically non-bloody Grade 3+ diarrhea) negative infectious workup beginning median 92.5 days (range: 22-210 days) after CAR-T 85 cytokine release syndrome resolution. Gut biopsies uniformly demonstrated inflammation, including intra-epithelial lymphocytosis villous blunting. In one case where CAR-specific immunofluorescence stains were available, CAR presence was confirmed within the lamina propria. Systemic corticosteroids initiated 10 patients (71%) 25.5 symptom onset, improvement 40%. Subsequent infliximab or vedolizumab led to 50% 33% corticosteroid-refractory patients, respectively. Five (36%) have died from bowel perforation treatment-emergent sepsis. conclusion, IEC-associated is distinct but rare complication typically 1-3 months infusion. Thorough diagnostic essential, evaluation potential malignancies. The early use may potentially hasten resolution lower reliance on high-dose during post-CAR-T period.

Language: Английский

Second primary malignancies after CAR T-cell therapy: A systematic review and meta-analysis of 5,517 lymphoma and myeloma patients DOI

Tobias Tix,

Mohammad Alhomoud, Roni Shouval

et al.

Clinical Cancer Research, Journal Year: 2024, Volume and Issue: 30(20), P. 4690 - 4700

Published: Sept. 11, 2024

Abstract Purpose: Chimeric antigen receptor (CAR) T-cell therapy is a potent immunotherapy for hematologic malignancies, but patients can develop long-term adverse events, including second primary malignancies (SPM) that impact morbidity and mortality. To delineate the frequency subtypes of SPMs following CAR-T in lymphoma myeloma, we performed systematic review meta-analysis. Experimental Design: A literature search was conducted MEDLINE, Embase, Cochrane CENTRAL databases. Following extraction SPM cases assignment malignant origin, analyzed point estimates using random effects models. Results: We identified 326 across 5,517 from 18 clinical trials 7 real-world studies. With median follow-up 21.7 months, overall estimate 6.0% (95% confidence interval, 4.8%–7.4%). were associated with treatment setting (clinical > studies), duration follow-up, number prior lines, which each confirmed as independent study-level risk factors meta-regression model. subgroup meta-analysis four randomized versus standard-of-care revealed similar either strategy (P = 0.92). In distribution analysis subtypes, most common entity (37%), followed by solid tumors (27%) non-melanoma skin cancers (16%). represented small minority events (1.5%). noted disease- product-specific variations distribution. Conclusions: These data raise awareness clinically relevant event receiving CAR therapy. However, our findings do not indicate higher previous strategies.

Language: Английский

Citations

19
T cell malignancies after CAR T cell therapy in the DESCAR-T registry DOI Creative Commons
Rémy Duléry, Vincent Guiraud, Sylvain Choquet

et al.

Nature Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 8, 2025

Language: Английский

Citations

9
Long-term safety of lentiviral or gammaretroviral gene-modified T cell therapies DOI
Julie K. Jadlowsky, Elizabeth O. Hexner, Amy Marshall

et al.

Nature Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 20, 2025

Language: Английский

Citations

6
CD4+ T-Cell Lymphoma Harboring a Chimeric Antigen Receptor Integration in TP53 DOI
Karlo Perica, Nayan Jain, Michael Scordo

et al.

New England Journal of Medicine, Journal Year: 2025, Volume and Issue: 392(6), P. 577 - 583

Published: Feb. 5, 2025

Malignant T-cell transformation after chimeric antigen receptor (CAR) therapy has been described, but the contribution of CAR integration to oncogenesis is not clear. Here we report a case lymphoma harboring lentiviral in known tumor suppressor, TP53, which developed patient with multiple myeloma B-cell maturation (BCMA) therapy.

Language: Английский

Citations

5
CAR T-cell-associated secondary malignancies challenge current pharmacovigilance concepts DOI Creative Commons
Philipp Berg, Gabriele Ruppert‐Seipp, Susanne Müller

et al.

EMBO Molecular Medicine, Journal Year: 2025, Volume and Issue: 17(2), P. 211 - 218

Published: Jan. 6, 2025

Abstract Suspected adverse reactions following chimeric antigen receptor T-cell (CAR T) treatment include more and cases of secondary malignancies. The causality assessment such suspected challenges established evaluation practices due to (i) patient product-specific risk factors (ii) incomplete data available with post-marketing reports submitted competent authorities. This is particular relevance for gene therapy products that integrate into the host genome. We present a summary case related different CAR T rationale assessment. In this context, possible pathophysiologic mechanisms differences between be taken account are discussed. unparalleled complexity follow-up multistep process cancer development necessitates case-by-case consideration. highlights in pharmacovigilance advanced medicinal underlines importance testing vector presence, integration location expression profile an informed malignancies aim obtain better understanding contributing factors.

Language: Английский

Citations

4
CAR+ T-Cell Lymphoma after Cilta-cel Therapy for Relapsed or Refractory Myeloma DOI
Simon J. Harrison, Cyrille Touzeau, Nicolas Kint

et al.

New England Journal of Medicine, Journal Year: 2025, Volume and Issue: 392(7), P. 677 - 685

Published: Feb. 12, 2025

We describe two patients in whom malignant monoclonal T-cell lymphoproliferation developed after administration of chimeric antigen receptor (CAR) therapy with ciltacabtagene autoleucel (cilta-cel) the phase 3 CARTITUDE-4 trial. Monoclonal T cells from both had detectable CAR transgene expression and integration. The clinicogenomic features these transgenic lymphoproliferative neoplasms suggest that multiple potential intrinsic or extrinsic factors (or both) contributed to their pathogenesis, such as transduction preexisting TET2-mutated cells, followed by acquisition further oncogenic genomic variants. Other contributors include germline variation, viral infections, previous treatment for myeloma. In absence direct evidence, contribution insertional mutagenesis development lymphoma is currently unclear. (Funded Johnson & Legend Biotech USA; ClinicalTrials.gov number, NCT04181827.).

Language: Английский

Citations

3
Safety of CAR T-cell therapy for cancer in pre-existing autoimmune or inflammatory disease: a retrospective comparative cohort study DOI
Kathleen M.M. Vanni,

Kaitlin R McCarter,

Xiaosong Wang

et al.

The Lancet Rheumatology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

1
Multiomic profiling of T cell lymphoma after therapy with anti-BCMA CAR T cells and GPRC5D-directed bispecific antibody DOI
Till Braun, Michael Rade, Maximilian Merz

et al.

Nature Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 21, 2025

Language: Английский

Citations

1
Living Bacteria: A New Vehicle for Vaccine Delivery in Cancer Immunotherapy DOI Open Access
Min Yang, Peiluan Zhong, Pengcheng Wei

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(5), P. 2056 - 2056

Published: Feb. 26, 2025

Cancer vaccines, aimed at evolving the human immune system to eliminate tumor cells, have long been explored as a method of cancer treatment with significant clinical potential. Traditional delivery systems face challenges in directly targeting cells and delivering adequate amounts antigen due hostile microenvironment. Emerging evidence suggests that certain bacteria naturally home on tumors modulate antitumor immunity, making bacterial vectors promising vehicle for precision vaccines. Live vehicles offer several advantages, including colonization, precise drug delivery, stimulation, them compelling option immunotherapy. In this review, we explore mechanisms action behind living bacteria-based recent progress popular chassis, strategies specific payload biocontainment ensure safety. These approaches will lay foundation developing an affordable, widely applicable vaccine system. This review also discusses future opportunities harnessing bacterial-based vaccines enhanced therapeutic outcomes treatment.

Language: Английский

Citations

1
Restoration of LAT activity improves CAR T cell sensitivity and persistence in response to antigen-low acute lymphoblastic leukemia DOI Creative Commons

Catherine Pham‐Danis,

A. Novak, Etienne Danis

et al.

Cancer Cell, Journal Year: 2025, Volume and Issue: 43(3), P. 482 - 502.e9

Published: March 1, 2025

Chimeric antigen receptor (CAR) T cells induce responses in patients with relapsed/refractory leukemia; however, long-term efficacy is frequently limited by relapse. The inability to target antigen-low an intrinsic vulnerability of second-generation CAR and underlies most relapses following CD22BBz cell therapy. Here, we interrogate signaling response low find inefficient phosphorylation the linker for activation (LAT) limiting downstream signaling. To overcome this, designed adjunctive LAT-activating (ALA-CART) platform, pairing a LAT-CAR incorporating intracellular domain LAT. ALA-CART demonstrate reduced differentiation during manufacturing increased LAT phosphorylation, MAPK signaling, AP-1 activity. show improved cytotoxicity, proliferation, persistence, against leukemias that were refractory clinically active cells. Restoration through platform represents promising strategy overcoming multiple mechanisms failure.

Language: Английский

Citations

1