High HT Score Associated With Poor Outcomes After Brexu-cel in R/R MCL

"The HT score enables early risk-stratification of patients [with MCL] into a high vs low risk for prolonged neutropenia, severe infections, and poor survival outcomes prior to brexu-cel infusion," according to the study authors.

Patients with relapsed/refractory mantle cell lymphoma (MCL) who had a high CAR-HEMATOTOX (HT) score appeared to be more likely to have severe hematologic toxicities, infections, and worsened treatment outcomes following administration of brexucabtagene autoleucel (brexu-cel; Tecartus), according to findings from a study published in American Journal of Hematology.

Overall, patients treated with brexu-cel experienced severe neutropenia for a median of 8 days (95% CI, 7-9), and 88% (n = 91) had an absolute neutrophil count drop below 500 per μL within the first 30 days of infusion. Additionally, 57% and 51% of patients, respectively, had severe thrombocytopenia and anemia.

Investigators noted a median duration of severe neutropenia of 14 days in patients with a high HT score compared with 6 days in those with a low HT score (P <.0001). The univariate analysis highlighted an association between HT score and duration of severe neutropenia (r = +0.58, P <.0001; β1 = 4.96). In the high and low HT score patients, respectively, rates of protracted severe neutropenia were 81% vs 41% (P <.0001), and protracted profound neutropenia occurred in 66% vs 30% (P = .0004).

Patients with a high HT score more frequently required support with granulocyte colony stimulating factor (70%) than those with a low HT score (45%; P = .01). Additionally, 13% of patients with a high HT score and 4% of those with a low HT score received TPO agonists.

“The HT score enables early risk-stratification of patients [with MCL] into a high vs low risk for prolonged neutropenia, severe infections, and poor survival outcomes prior to brexu-cel infusion,” the study authors wrote. “The score will enable individualized toxicity management strategies that spare over-treatment in low-risk candidates, while mitigating the sequelae of toxicity in high-risk patients. Finally, the score could aid with patient selection and help to identify ultra-high-risk candidates in need of further treatment optimization.”

Investigators of this study assessed toxicity and survival outcomes in patients with relapsed/refractory MCL who received brexu-cel between December 2015 and July 2022. The study included 103 patients, 89 of whom received treatment in a standard-of-care setting, and 14 of whom were treated as part of the phase 2 ZUMA-2 trial (NCT02601313). Patients underwent lymphodepletion with fludarabine and cyclophosphamide.

Investigators calculated HT scores on the day of lymphodepletion via the German Lymphoma Alliance online calculator, with low scores ranging from 0 to 1 (n = 56) and high scores ranging from 2 to 7 (n = 47). Efficacy end points including overall survival (OS) and progression-free survival (PFS) were evaluated based on Lugano criteria. Additionally, investigators assessed for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) per American Society for Transplantation and Cellular Therapy consensus criteria.

The median patient age was 66 years (range, 49-89), the median ECOG performance status was 1 (interquartile range [IQR], 0-1), and patients received a median of 3 (IQR, 2-4) prior lines of treatment. Additionally, 79% of patients underwent bridging therapy. Investigators highlighted that 75% of patients had an intermediate or high-risk simplified MCL international prognostic index score and that 40% of the population had blastoid or pleomorphic histology.

The median PFS was 25.2 months, and the median OS was not reached in the overall population with a median follow-up of 15.4 months. In the high HT score and low HT score groups, respectively, the median PFS was 9.2 months vs not reached (P <.0001), and the median OS was 25.6 months vs not reached (P <.0001). Investigators highlighted that HT score was an independent predictor of worse PFS (adjusted HR, 3.7; 95% CI, 1.7-8.0; P <.001) and OS (adjusted HR, 5.6; 95% CI, 1.8-17.2; P = .002).

Grade 3 or higher CRS and ICANS occurred in 6% and 25% of patients in each respective cohort. There were no statistically significant differences in the incidence of CRS or ICANS based on HT scores. Patients with a high and low HT score both had a median hospitalization duration of 18 days (P = .7).

Investigators reported 50 infection events in 34 patients, the most common of which were bloodstream infections (40%), lower respiratory tract infections (24%), and gastrointestinal tract infections (16%). Based on multivariate analysis of pre-CAR T factors in lymphodepletion, HT score was an independent risk factor that correlated with severe infections (adjusted odds ratio, 6.5; 95% CI, 1.4-31.1).

The any-grade maximal infection rate was 43% in patients with a high HT score vs 25% in those with a low HT score (P = .09); the rates of severe infections in each respective group were 30% vs 5% (P = .001). The estimated NRM rate at 1 year was 10.4% in the entire cohort, 17.3% in the high HT score group, and 4.6% in the low HT score group (P = .04).

Reference

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. Am J Hematol. Published online August 16, 2023. doi:10.1002/ajh.27056