CAR-Hematotox score predicts toxicity, infections, and clinical outcomes in MCL 

Patients with relapsed or refractory mantle cell lymphoma (MCL) and a high CAR-Hematotox score had an increased risk for haematological toxicity, infections, and an inferior progression-free survival and overall survival following treatment with brexucabtagene autoleucel (brexu-cel). According to the authors, stratifying patients for the risk of haematological toxicity may aid physicians to tailor the management of their patients.

CAR T-related haematological toxicity is a frequently occurring phenomenon, and prolonged cytopenia and complications due to infections contribute to the toxicity burden of CD19-directed CAR T therapy [1]. “The CAR-Hematotox score predicts the risk for prolonged neutropenia, severe infections, and poor treatment outcomes after CD19 CAR T-cell therapy,” said Dr Kai Rejeski (LMU Munich, Germany) [1,2]. The use of this tool in patients with relapsed/refractory MCL undergoing CD19 CAR T-cell therapy has not yet been established. Therefore, the current international, multicentre, retrospective study analysed the applicability of the CAR-Hematotox score in 103 patients with relapsed/refractory MCL receiving brexu-cel.

At baseline, high CAR-Hematotox scores (HT-high) were related to aggressive disease biology, increased bone marrow infiltration, a higher number of prior treatments, and increased disease activity. It was demonstrated that patients with HT-high had higher risk for haematologic toxicity than patients with HT-low: neutropenia (median 14 vs 6 days; P<0.001); aplastic phenotype (47% vs 0%; P<0.001); severe anaemia (45% vs 11%; P<0.0001); profound (85% vs 46%; P<0.0001) or prolonged cytopenia (66% vs 30%; P<0.0004). Furthermore, severe infections were more common in HT-high patients than in HT-low patients (30% vs 5%; P=0.001), mostly driven by an increase in bacterial infections (28% vs 5%; P=0.002). Finally, after 720 days of follow-up, HT-high scores were associated with poorer progression-free survival (38% vs 79%; P<0.0001) and overall survival (52% vs 90%; P=0.00016).

In summary, HT-high patients had an increased risk to develop severe haematotoxicity and infectious complications and had a reduced progression-free and overall survival compared with HT-low patients. Dr Rejeski commented that a risk stratification for haematological toxicity and infections should be performed before lymphodepletion in order to initiate prophylactic strategies in time.

1. Rejeski K, et al. Blood. 2021;138(24):2499–2513.
2. Rejeski K, et al. The CAR-Hematotox Score Identifies Patients at High Risk for Hematological Toxicity, Infections and Poor Clinical Outcomes Following BrexucabtageneAutoleucel in Relapsed/Refractory Mantle Cell Lymphoma. Abstract 264, ASH 64^th Annual Meeting, 10–13 December 2022, New Orleans, LA, USA.

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Posted on 20 February, 2023