Piotr Wysocki: Nonrelapse mortality in CAR-T-treated patients. Beware of infections!
Piotr Wysocki recently posted on LinkedIn:
“Cordas DM et al. conducted a systematic review and meta-analysis of data on nonrelapse mortality (NRM) after CAR T cell therapy in lymphoma and multiple myeloma patietns. The researchers identified 7,604 patients across 18 clinical trials and 28 real-world studies, with 574 nonrelapse deaths reported. 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.
The majority of NRM was due to infections (50.9%), followed by other malignancies (7.8%) and cardiovascular/respiratory events (7.3%) with CAR T cell-related adverse events (immune effector cell-associated neurotoxicity syndrome/neurotoxicity, cytokine release syndrome, and hemophagocytic lymphohistiocytosis) reported only in 11.5% of nonrelapse deaths (cumulatively 11.5%).
Detailed characteristics of NRM were as follows:
Infections – 50.9%
- The causative pathogen was unspecified in 64.7% of these cases.
- COVID-19 was responsible for 53.4% of the infection-related deaths with identified pathogens.
- Other infection-related deaths were caused by:
- fungal infections – 9.4%
- bacterial infections – 21.4%
- non-COVID-19 viral infections – 4.8%
Secondary Malignancies – 7.8%
- myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) – 33.3%
- carcinomas – 22.2%
- malignancy-related deaths unspecified – 42.2%
Cardiovascular or Respiratory Events – 7.3%
- respiratory failure – 23.3%
- thromboembolic events in the CNS – 20.9%
- cardiac arrest – 18.6%
Typical CAR T Cell Side Effects – 11.5%
- ICANS/neurotoxicity – 5.2%
- CRS – 4.7%
- hemorrhage – 3.3%
- secondary hemophagocytic lymphohistiocytosis – 1.6%
Real-World vs. Clinical Trials
- immune-related side effects-related deaths – 7.9% in clinical trials (CT) v. 16.6% real-world (RW)
- CVR e- 16.5% (CT) v. 6.2% (RW)
- Infection-related deaths – 59.1% (CT) v. 64.6% (RW)”
Authors: David M. Cordas dos Santos, Tobias Tix, Roni Shouval, Anat Gafter-Gvili, Jean-Baptiste Alberge, Edward R. Scheffer Cliff, Sebastian Theurich, Michael von Bergwelt-Baildon, Irene M. Ghobrial, Marion Subklewe, Miguel-Angel Perales, and Kai Rejeski
Source: Piotr Wysocki/LinkedIn
Piotr Wysocki leads the Clinical Oncology Department at University Hospital and the Faculty of Oncology at Jagiellonian University-Medical College in Krakow, Poland. As an advisor to the Polish Ministry of Health, he shapes the national cancer strategy.
His clinical expertise spans the systemic treatment of breast, gynecologic, and genitourinary cancers, with a focus on developing innovative metronomic chemotherapy-based therapies for advanced cancer patients who have undergone prior treatment.
Read other posts by Piotr Wysocki published on OncoDaily.