Incidence and risk factors associated with bleeding and thrombosis following chimeric antigen receptor T-cell therapy.

Abstract

Bleeding and thrombotic events are an emerging toxicity associated with chimeric antigen receptor (CAR) therapies. To determine their incidence, we retrospectively analyzed consecutive adult patients (N = 127) with large B-cell lymphoma (LBCL) or B-cell acute lymphoblastic leukemia (B-ALL) treated from 2017 through 2020 with axicabtagene ciloleucel (axi-cel; n = 89) or a bispecific CD19/CD22 CAR (n = 38). Twelve (9.4%) and 8 (6.3%) patients developed bleeding and thrombosis within the first 3 months, respectively. In the axi-cel subgroup, these occurred in 11.2% and 6.7%, respectively. Bleeding occurred between days 8 and 30 (median, 17.5) and thrombosis between days 2 and 91 (median, 29). Bleeding sites included genitourinary, soft tissue, intracranial, gastrointestinal, and pulmonary and were associated with features of consumptive coagulopathy. On univariate analysis, patients with bleeding were older, had lower baseline platelets (86 × 103/μL vs 178 × 103/μL; P < .01), lower platelet and fibrinogen nadirs , and elevated lactate dehydrogenase. Immune effector cell (IEC)-associated neurotoxicity syndrome (ICANS) grade ≥3 was associated with increased bleeding (50% vs 15%; P = .01), thrombosis (50% vs 16%; P = .04), prothrombin time prolongation, hypofibrinogenemia, and elevated D-dimer. Low pretreatment platelet counts were associated with bleeding in a multivariate logistic regression model. Patients with thrombocytopenia or severe ICANS are at increased risk of bleeding and should be closely monitored, particularly within the first month after CAR therapy. Future studies in larger cohorts should assess risk factors for systemic coagulopathies in CAR T therapy, including their association with neurotoxicity.

• Authors: Andrew Johnsrud, Juliana Craig, John Baird, Jay Spiegel, Lori Muffly, James Zehnder, John Tamaresis, Robert Negrin, Laura Johnston, Sally Arai, Judith Shizuru, Robert Lowsky, Everett Meyer, Wen-Kai Weng, Parveen Shiraz, Andrew Rezvani, Theresa Latchford, Crystal Mackall, David Miklos, Matthew Frank, Surbhi Sidana
• Journal: Blood advances (Blood Adv) Vol. 5 Issue 21 Pg. 4465-4475 (11 09 2021) ISSN: 2473-9537 [Electronic] United States
• PMID: 34521106 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © 2021 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.

Chemical References

• Receptors, Chimeric Antigen

Topics

• Cell- and Tissue-Based Therapy
• Humans
• Incidence
• Receptors, Chimeric Antigen
• Retrospective Studies
• Risk Factors
• Thrombosis (epidemiology, etiology)