Scoring system predicts infection risk, treatment outcomes after CAR-T
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Researchers from Europe and the U.S. developed a hematologic toxicity score that can predict which patients are more likely to develop severe infections after chimeric antigen receptor T-cell therapy.
Patients who scored higher on the scale had inferior treatment outcomes compared with those who scored lower, study results presented at European Society for Blood and Marrow Transplantation-European Hematology Association (EHA) 4th European CAR T-cell Meeting showed.
Background
Patients who undergo CAR T-cell therapy often experience prolonged cytopenias, according to Kai Rejeski, MD, clinician-scientist at Ludwig Maximilian University Hospital in Munich.
"They are sort of perplexing to us because they often occur long after lymphodepletion chemotherapy and the resolution of clinical cytokine release syndrome,” he told Healio.
His group initially set out to identify which markers could be used to risk-stratify patients for hematologic toxicity before CAR-T. They developed the CAR-HEMATOTOX model, which considers measurements of hematopoietic reserve and baseline inflammation 5 days before lymphodepletion.
“On the basis of this, you can risk-stratify these patients as high risk or low risk,” Rejeski said.
The CAR-HEMATOTOX scoring system has been validated via two separate research cohorts in Europe, Rejeski said.
Now he and his team are exploring in a larger treatment cohort whether patients with high CAR-HEMATOTOX scores have higher infection rates. They also are assessing the impact of post-CAR-T infections on treatment outcomes.
Methodology
Rejeski and colleagues conducted a multicenter retrospective analysis of 248 patients (median age 63 years; range, 19-83; 58% male) who received axicabtagene ciloleucel (Yescarta, Kite Pharma/Gilead Sciences) or tisagenlecleucel (Kymriah, Novartis) as standard-of-care therapy for relapsed or refractory diffuse large B-cell lymphoma, with particular focus on infections that occurred within 90 days of infusion.
The CAR-HEMATOTOX score assigns point values to baseline clinical variables and incorporates hematopoietic reserve values (absolute neutrophil count, hemoglobin, platelet count) and markers of inflammation (C-reactive protein and ferritin) prior to lymphodepletion.
Individual variables are each assigned a 0 to 2 point value. An overall total of 2 or more represents a high CAR-HEMATOTOX score.
The investigators used a five-point grading scale to quantify infection severity, with scores of grade 3 or higher considered severe infections that required mitigating therapies and/or hospitalization.
Key findings
Patients with a high CAR-HEMATOTOX score had significantly longer median duration of severe neutropenia after CAR-T than patients with low CAR-HEMATOTOX scores (13 days vs. 6 days; P < .001).
A multivariate analysis showed patients with high CAR-HEMATOTOX scores had increased likelihood of severe infections (adjusted OR = 7.7; 95% CI, 3.4-17.3). Forty percent of patients with high scores developed severe infections — including six that resulted in death — compared with 8% of patients with low CAR-HEMATOTOX scores.
Patients with high CAR-HEMATOTOX scores also demonstrated significantly worse clinical outcomes with respect to median PFS (3.4 months vs. 12.6 months; P = .00031) and median OS (9.1 months vs. not reached; P < .0001).
Clinical implications
The scoring system’s prognostic value allows clinicians to consider interventions that can possibly reduce infection risk and improve patient outcomes, Rejeski said. These include:
- early or prophylactic administration of granulocyte colony-stimulating factor;
- prophylactic administration of anti-infection agents, especially mold-active antifungals; and
- close monitoring in an intermediate-care ward with a low threshold for escalation to intensive care.
Further validation of the scoring system via prospective phase 2 studies is planned, Rejeski said. Researchers also intend to explore whether it can be applied to other diseases, such as mantle cell lymphoma or multiple myeloma.
Efforts are underway to incorporate the CAR-HEMATOTOX scoring system into existing clinical care apps for hematologist-oncologists, including the myTcell mobile app developed at Ludwig Maximilian University.
"I think it would be very cool if we could integrate the scoring system into these apps and make it clinically useful for as many centers as possible,” Rejeski said.
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Rejeski K, et al. Abstract PT02-3. Presented at: European Society for Blood and Marrow Transplantation-European Hematology Association 4th European CAR T-cell Meeting; Feb. 10-12, 2022.
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