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.
Flow-based human tissue models show stronger T-cell activity than static cultures, with blinatumomab inducing significant B-cell killing and cytokine release. Sartorius has introduced a 96-well multi-organ tox plate for drug toxicity testing, while in vitro systems are increasingly used as new approach methodologies to complement animal models.
An armored GPC3-directed CAR T-cell therapy showed manageable safety and antitumor activity in refractory HCC, with 44.4% objective responses and 14.2-month median overall survival in a first-in-human trial.
Multiple myeloma immunotherapies like bispecific antibodies and CAR-T cells show high response rates and prolonged survival, but access is hindered by the need for initial hospital stays for bispecifics. Research indicates mezigdomide can reverse T cell exhaustion to boost these therapies, while longer-term CARVYKTI data show significant survival benefits.
The FDA granted RMAT designation to Allogene’s cema-cel for first-line LBCL consolidation and Cellectis’ lasme-cel for r/r B-ALL. Both allogeneic CAR-T therapies showed promising early efficacy and safety, with cema-cel also receiving Fast Track status.
Presenters at the 2026 ICE-T Conference discussed the growing role of bispecific antibodies and CAR T-cell therapies in hematologic cancers, while a separate study found that structural instability of linkers in symmetric bispecific antibodies could pose manufacturing hurdles.
New CAR T-cell data show 100% MRD negativity in high-risk smoldering multiple myeloma, a novel CAR T approach for AML, and a new T-cell pathway, while a case report warns of a rare therapy-related complication.
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.
| NCT ID | Title | Status | Phase |
|---|---|---|---|
| NCT07657312 |
Infliximab for Cytokine Release Syndrome Prophylaxis During Teclistamab or Talquetamab Therapy in Patients With Relapsed or Refractory Myeloma |
RECRUITING | PHASE2 |
| 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 |
WITHDRAWN | 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 |
