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.
Phase I CARLYSLE trial data show CAR-T therapy obe-cel induces remission in severe refractory lupus with a favorable safety profile. Separate case report documents two successful pregnancies after dual-target CAR-T therapy with no transmission to infants.
Swissmedic has authorized three orphan drugs for rare diseases: Breyanzi for mantle cell lymphoma, Alhemo for haemophilia A and B, and Ekterly for hereditary angioedema. The decisions include a new indication extension for Breyanzi, an expanded indication for Alhemo, and the initial authorization of Ekterly as part of a joint international regulatory initiative.
Long-term results from the phase III TRIANGLE trial show ibrutinib-based regimens improve survival in younger mantle cell lymphoma patients, while the ECHO trial establishes a new standard for older patients. Advances in CAR T-cell and bispecific antibody therapies are reshaping treatment for this rare blood cancer. The findings were presented at the annual MCL Consortium meeting.
The treatment landscape for multiple myeloma is evolving rapidly with T-cell engaging therapies like bispecific antibodies and CAR T-cell treatments shifting care toward a chronic condition with potential treatment breaks. This evolution is creating new side effect management challenges and complicating clinical trial design as sponsors grapple with selecting comparator arms and adapting to a rapidly shifting standard of care.
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.
| NCT ID | Title | Status | Phase |
|---|---|---|---|
| NCT07499128 |
Continuous Temperature Monitoring (CTM) for Cytokine Release Syndrome (CRS), an Immune-Related Adverse Event |
ENROLLING_BY_INVITATION | 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 |
