HT Scoring Identifies Risk and Outcomes of CAR T Therapy for MCL

Malignant cells of mantle cell lymphoma: © David A Litman - stock.adobe.com

Analyses show that a hematoxicity scoring system could identify poor treatment outcomes for patients with mantle cell lymphoma (MCL) treated with brexucabtagene autoleucel (brexu-cel; Tecartus) chimeric antigen receptor (CAR) T-cell therapy, according to a study in the American Journal of Hematology.¹

A high CAR-FYI HEMATOTOX (HT) score was independently associated with severe hematoxicity, higher incidence of infection, and poor progression-free survival (PFS) and overall survival (OS) rates.

In the study, the cohort with high HT scores experienced prolonged neutropenia (median 14 v 6 days; P < .001) and an increased rate of infection (30% v 5%; P = .001). Patients with high HT scores also experienced worse 90-day complete response rates (68% v 93%; P = .002), PFS (median 9 months v not-reached; P < 0.0001), and OS (median 26 months v not reached; P < .0001). Low HT scores were also associated with improved overall response (100% v 85%; P = 0.003).

According to authors of the study, “the HT score enables early risk-stratification of [patients with] MCL into high vs low risk for prolonged neutropenia, severe infections, and poor survival outcomes prior to brexu-cel infusion.” The authors added that the score could also help clinicians identify “ultra-high-risk patients in need of further treatment optimization.”¹

Investigators assessed 103 patients with relapsed or refractory MCL receiving brexu-cel at a median follow-up of 15.4 months. The median age was 66 years (range, 49-89), and patients received a median of 3 prior treatment lines.¹ Patient HT scores were calculated on the day of lymphodepletion (day -5) using the German Lymphoma Alliance’s calculator. The calculator accounts for 5 metrics of hematoxicity, including platelet count, absolute neutrophil count, hemoglobin, C-reactive protein, and ferritin, with additional weighting of the baseline platelet count and ferritin levels.² Fifty-six patients had low HT scores (0-1) and 47 patients had high HT scores (2-7). The median HT score was 1.¹

Patients with high HT scores more often exhibited an aplastic phenotype of neutrophil recovery, which was not observed in the low HT score group (47% vs 0%; P < .0001). Investigators observed a significant positive correlation between HT score and duration of severe neutropenia. The high HT group also had more patients with prolonged neutropenia (66% v 30%; P = .0004).

Furthermore, patients with high HT scores experienced higher rates of early (until day +30) and late (day +31 to day +100) severe thrombocytopenia and anemia. These conditions led to more required platelet transfusions.

Regarding infection rates, the high HT group experienced more infections of any grade (43% v 25%; P = .09) and more severe infections (30% v 5%; P = .01). No fatal infection was observed in the low HT group, while 7 deaths were attributed to infection in the high HT group.

Study authors noted some limitations, which include that their analysis was retrospective and uncontrolled, and follow-up still remains short. Further analysis should evaluate HT score in a prospective manner, and response assessment should be performed by an independent review committee, according to authors.¹

REFERENCES

1. Rejeski K, Wang Y, Albanyan O, et al. The CAR-HEMATOTOX score identifies patients at high risk for hematological toxicity, infectious complications, and poor treatment outcomes following brexucabtagene autoleucel for relapsed or refractory MCL [published online ahead of print, 2023 Aug 16]. Am J Hematol. 2023;10.1002/ajh.27056. doi:10.1002/ajh.27056

2. Scores. German Lymphoma Alliance. Accessed October 9, 2023. https://tinyurl.com/2uy7cath