CAR‑HEMATOTOX Score Shows Prognostic Utility for CAR‑T Therapy in Relapsed/Refractory Multiple Myeloma

The CAR-HEMATOTOX (HT) score has prognostic value for both toxicity and treatment response in patients with relapsed/refractory (R/R) multiple myeloma (MM) receiving B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T-cell therapy, according to research published in Journal of Hematology & Oncology.

“We previously developed the [HT] score to model CAR-T related hematotoxicity in a R/R large B-cell lymphoma (LBCL) patient cohort,” the researchers explained in their report. “Notably, the score was associated with an increased rate of severe infections, particularly bacterial infections, and poor treatment outcomes in LBCL patients receiving commercial CD19-directed CAR-T in the 3rd line setting.”

The team conducted a multicenter retrospective observational study to examine the utility of the HT score to predict toxicity and survival outcomes in patients with R/R MM receiving standard-of-care idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel).

The study included data from 113 patients treated (ide-cel, n=106; cilta-cel, n=7) between April 2021 and July 2022 at 6 international CAR-T centers. The HT score, which integrates factors related to pre-CAR-T hematopoietic reserve (such as hemoglobin, absolute neutrophil count, and platelet count) and baseline inflammatory state (such as C-reactive protein or ferritin) was calculated prior to lymphodepleting chemotherapy.

Patients had a median age of 65 years (range, 39-81 years) and median ECOG performance status score of 1. They had received a median of 6 prior lines of therapy, with 88% having received prior autologous stem cell transplantation. At baseline, the HT score was low for 63 patients (55%; score 0-1) and high for 50 patients (44%; score ≥2).

Patients in the HT-high group, compared with those in the HT-low group, experienced prolonged severe neutropenia (median, 9 vs 3 days; P <.001), an increased rate of severe infection (40% vs 5%; P <.001), and a higher rate of severe ICANS (immune effector cell-associated neurotoxicity syndrome grade ≥ 3, 16% vs 0%; P <.001).

The researchers found that 1-year nonrelapse mortality was significantly higher in the HT-high group than the HT-low group (13% vs 2%; P =.019) and was predominantly attributed to fatal infections.

They also found that the HT-high group, compared with the HT-low group, had a lower rate of very good partial response or better (≥VGPR, 44% vs 70%; P =.01) and inferior progression-free survival (median, 5 vs 15 months; P <.001) and overall survival (median, 10.5 months vs not reached; P <.001).

“The extensive validation of the HT score demonstrates the importance of pre-CAR-T hematopoietic reserve and baseline inflammatory state for the subsequent development of toxicity and early progression in patients receiving BCMA-directed CAR-T,” the study authors explained. “The score could enable tailored interventions for CAR-T-related toxicity according to the individual risk profile of each patient, and help identify CAR-T candidates in need of combinatorial and/or novel therapeutic strategies.”

Limitations of the study included the retrospective design and limited follow-up duration.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of authors’ disclosures. 

Reference

Rejeski K, Hansen DK, Bansal R, et al. The CAR-HEMATOTOX score as a prognostic model of toxicity and response in patients receiving BCMA-directed CAR-T for relapsed/refractory multiple myeloma. J Hematol Oncol. 2023;16(1):88. doi:10.1186/s13045-023-01465-x

This article originally appeared on Hematology Advisor