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NonRelapse Mortality CAR-T Death
What is nonrelapse mortality CAR-T death? While I agree that chimeric antigen receptor (CAR) T cell therapy represents the future of MM therapy going forward, I also think that it is important to study this therapy carefully.
At this stage, there are still lots of adverse events that can lead to death aka non-relapse mortality in CAR-T treatment.
When I underwent an autologous stem cell transplant in late 1995, stem cell transplants, both autologous and allogeneic, were said to be the future of MM therapy too.
For a time I gave serious consideration to having an allogeneic stem cell transplant until I figured out that the death rate from an allo SCT was twice that of an auto SCT and that the side effects were particularly serious.
The study linked below focuses only on “nonrelapse mortality” (NRM) in CAR-T survivors- that is to say, patients who don’t diet of a relapse of their MM.
What NRM deaths result from CAR-T therapy?
- Cytokine Release Syndrome (CRS):
- CRS is a systemic inflammatory response triggered by the rapid activation and proliferation of CAR-T cells. It can cause high fever, low blood pressure, difficulty breathing, and multi-organ failure. Severe CRS can be life-threatening if not managed promptly.
- Neurotoxicity:
- Neurological side effects, sometimes referred to as CAR-T-cell-related encephalopathy syndrome (CRES), can include confusion, seizures, delirium, and even coma. Severe neurotoxicity can result in permanent damage or death.
- Infections:
- Patients receiving CAR-T therapy can become immunocompromised, increasing their susceptibility to infections. These infections can sometimes be severe and fatal.
- Tumor Lysis Syndrome (TLS):
- TLS occurs when a large number of cancer cells are killed off rapidly, releasing their contents into the bloodstream. This can lead to severe metabolic imbalances, acute kidney failure, and other critical complications.
- Hematologic Toxicities:
- These include prolonged cytopenias (low blood cell counts), which can lead to complications like bleeding, anemia, and increased risk of infections, potentially resulting in death.
It is clear that CAR-T cell therapy has a great deal of potential as a MM therapy. However, I think it is essential that MM survivors understand both the risks and rewards for any and all therapies.
Are you considering CAR-T cell therapy? Email me at David.PeopleBeatingCancer@gmail.com
thank you,
David Emerson
- MM Survivor
- MM Cancer Coach
- Director PeopleBeatingCancer
A systematic review and meta-analysis of nonrelapse mortality after CAR T cell therapy
“Although chimeric antigen receptor (CAR) T cell therapy represents a transformative immunotherapy, it is also associated with distinct toxicities that contribute to morbidity and mortality.
In this systematic review and meta-analysis, we searched MEDLINE, Embase and CINAHL (Cochrane) for reports of nonrelapse mortality (NRM) after CAR T cell therapy in lymphoma and multiple myeloma up to March 2024.
After extraction of causes and numbers of death, we analyzed NRM point estimates using random-effect models. We identified 7,604 patients across 18 clinical trials and 28 real-world studies. NRM point estimates varied across disease entities and were highest in patients with mantle-cell lymphoma (10.6%), followed by multiple myeloma (8.0%), large B cell lymphoma (6.1%) and indolent lymphoma (5.7%).
Entity-specific meta-regression models for large B cell lymphoma and multiple myeloma revealed that axicabtagene ciloleucel and ciltacabtagene autoleucel were independently associated with increased NRM point estimates, respectively.
Of 574 reported nonrelapse deaths, over half were attributed to
- infections (50.9%), followed by
- other malignancies (7.8%) and
- cardiovascular/respiratory events (7.3%).
Conversely, the CAR T cell-specific side effects,
- immune effector cell-associated neurotoxicity syndrome/neurotoxicity,
- cytokine release syndrome and
- hemophagocytic lymphohistiocytosis,
represented only a minority of nonrelapse deaths (cumulatively 11.5%).
Our findings underline the critical importance of infectious complications after CAR T cell therapy and support the comprehensive reporting of NRM, including specific causes and long-term outcomes.