Cytokine release syndrome (CRS) is a systemic inflammatory syndrome triggered by rapid immune activation and cytokine release. It is most commonly recognized as a toxicity of CAR-T cell therapy and can range from mild constitutional symptoms to severe multiorgan dysfunction. Clinical monitoring and grading are central to management.
A phase II trial of TAK-007 CAR-NK therapy in R/R B-cell NHL showed a 60.9% overall response rate. Preclinical CAR-NKT therapy eliminated endometrial tumors in models. Optimized costimulatory domains (2B4-DAP12) boosted CAR-NK tumor killing.
The FDA approved Bristol Myers Squibb’s Breyanzi for adults with relapsed or refractory marginal zone lymphoma after at least two prior systemic therapies. In TRANSCEND FL, the CAR T therapy showed a 95.5% overall response rate and 62.1% complete response rate.
A phase 2 trial in high-risk smoldering multiple myeloma found all 20 patients treated with cilta-cel became MRD-negative within two months and remained so after 15.3 months. No disease progression, death, dose-limiting toxicities, or high-grade side effects were observed.
CAR-T toxicity management is shifting toward phenotype- and mechanism-based intervention. Key issues include CRS, ICANS, IEC-HS, and long-term risks of cytopenia and infection.
Kyverna Therapeutics reports positive long-term follow-up results for its CAR-T therapy miv-cel in generalized myasthenia gravis, with plans to submit a biologics license application in the first half of 2026. The company has $279.3 million in cash providing runway into 2028 to fund launch and Phase 3 trials.
The 2026 Tandem Meetings featured new data on CAR-T, allogeneic transplantation, and supportive care. Highlights included early efficacy signals for EB-103, KITE-753, Orca-T, and NXC-201, plus comparative cardiovascular safety data for lisocabtagene maraleucel.
A phase 1 trial shows denileukin diftitox administered before CAR-T therapy has a favorable safety profile and encouraging efficacy in high-risk DLBCL patients, with an 86% overall response rate and 77% one-year progression-free survival. The treatment demonstrated consistent regulatory T-cell depletion, supporting its immunomodulatory mechanism. Larger controlled studies are needed to confirm these preliminary findings.
A study of 366 patients found ide-cel CAR-T cell therapy achieved 81.6% overall response rate in patients 70 or older with relapsed/refractory multiple myeloma, with median progression-free survival of 18.9 months versus 5.7 months with standard regimens.
Real-world data from over 300 large B-cell lymphoma patients treated with axicabtagene ciloleucel show response rates and survival outcomes remarkably similar to pivotal trial results, with 86% overall response rate and 74% one-year survival.
The FDA has granted fast track designation to QRX003 for Netherton Syndrome and IBI3003 for relapsed or refractory multiple myeloma, while also accepting regulatory applications for other therapies addressing serious conditions with unmet medical needs.
| NCT ID | Title | Status | Phase |
|---|---|---|---|
| NCT07499128 |
Continuous Temperature Monitoring (CTM) for Cytokine Release Syndrome (CRS), an Immune-Related Adverse Event |
NOT_YET_RECRUITING | NA |
| NCT07390071 |
Multimodal Telerehabilitation in Patients Undergoing CAR-T Cell Immunotherapy |
RECRUITING | NA |
| NCT07169487 |
Adjunctive Methylene Blue for Immunotherapy-related CRS and ICANS: Phase I Study |
RECRUITING | PHASE1 |
| NCT06703216 |
Pre-emptive Anakinra for Cytokine Event Reduction |
NOT_YET_RECRUITING | PHASE1/PHASE2 |
| NCT06447376 |
Study of Cytokine Release Syndrome Prophylaxis and Treatment With Siltuximab Prior to Epcoritamab |
RECRUITING | PHASE1 |
| NCT06352866 |
Siltuximab for Cytokine Release Syndrome Prophylaxis Prior to tx w/ Teclistamab in RRMM |
WITHDRAWN | PHASE2 |
| NCT05905328 |
Study of CTO1681 for the Prevention and Treatment of CRS in DLBCL Patients Receiving CAR T-Cell Therapy |
RECRUITING | PHASE1/PHASE2 |
| NCT05414162 |
Multiparametric Cardiac MRI in Patients Under CAR T-cell Therapy |
RECRUITING | |
| NCT05349669 |
Jafron Haemoadsorption During Cardiopulmonary Bypass |
COMPLETED | PHASE2 |
| NCT05096052 |
PROlectin M, a Nucleocapsid TErminal GaleCTin Antagonist for COVID-19 |
UNKNOWN | PHASE3 |
