Tocilizumab for Cytokine Release Syndrome Management After Haploidentical Hematopoietic Cell Transplantation With Post-Transplantation Cyclophosphamide-Based Graft-Versus-Host Disease Prophylaxis

• Published in: Transplantation and cellular therapy 2023-08, Vol.29 (8), p.515.e1-515.e7
• Main Authors: Yao, Janny M., Otoukesh, Salman, Kim, Hanna, Yang, Dongyun, Mokhtari, Sally, Samara, Yazeed, Blackmon, Amanda, Arslan, Shukaib, Agrawal, Vaibhav, Pourhassan, Hoda, Amanam, Idoroenyi, Ball, Brian, Koller, Paul, Salhotra, Amandeep, Becker, Pamela, Curtin, Peter, Artz, Andrew, Aldoss, Ibrahim, Ali, Haris, Stewart, Forrest, Smith, Eileen, Stein, Anthony, Marcucci, Guido, Forman, Stephen J., Nakamura, Ryotaro, Al Malki, Monzr M.
• Format: Article
• Language: English
• Subjects: Aged; Cyclophosphamide - pharmacology; Cyclophosphamide - therapeutic use; Cytokine release syndrome; Cytokine Release Syndrome - drug therapy; Cytokine Release Syndrome - etiology; Cytokine Release Syndrome - prevention & control; Graft vs Host Disease - drug therapy; Graft vs Host Disease - prevention & control; Haploidentical hematopoietic cell transplantation; Hematopoietic Stem Cell Transplantation - adverse effects; Humans; Middle Aged; Post-transplant cyclophosphamide; Prospective Studies; Retrospective Studies; Tocilizumab; Transplantation Conditioning - adverse effects
• ISSN: 2666-6367; 2666-6367
• DOI: 10.1016/j.jtct.2023.05.008

Cytokine release syndrome (CRS) is a common complication after haploidentical hematopoietic cell transplantation (HaploHCT). Severe CRS after haploHCT leads to higher risk of non-relapse mortality (NRM) and worse overall survival (OS). Tocilizumab (TOCI) is an interleukin-6 receptor inhibitor and is commonly used as first-line for CRS management after chimeric antigen receptor T cell therapy, but the impact of TOCI administration for CRS management on Haplo HCT outcomes is not known. In this single center retrospective analysis, we compared HCT outcomes in patients treated with or without TOCI for CRS management after HaploHCT with post-transplantation cyclophosphamide- (PTCy-) based graft-versus-host disease (GvHD) prophylaxis. Of the 115 patients eligible patients who underwent HaploHCT at City of Hope between 2019 to 2021 and developed CRS, we identified 11 patients who received tocilizumab for CRS management (TOCI). These patients were matched with 21 patients who developed CRS but did not receive tocilizumab (NO-TOCI) based on age at the time of HCT (≤64 years or >65 years or older), conditioning intensity (myeloablative versus reduced-intensity/nonmyeloablative), and CRS grading (1, 2, versus 3-4). Instead of 22 controls, we chose 21 patients because there was only 1 control matched with 1 TOCI treatment patient in 1 stratum. With only 11 patients in receiving tocilizumab for CRS treatment, matching with 21 patients who developed CRS but did not receive tocilizumab, we had 80% power to detect big differences (hazard ratio [HR] = 3.4 or higher) in transplantation outcomes using a 2-sided 0.05 test. The power would be reduced to about 20% to 30% if the difference was moderate (HR = 2.0) using the same test. No CRS-related deaths were recorded in either group. Median time to neutrophil engraftment was 21 days (range 16-43) in TOCI and 18 days (range 14-23) in NO-TOCI group (HR = 0.55; 95% confidence interval [CI] = 0.28-1.06, P = .08). Median time to platelet engraftment was 34 days (range 20-81) in TOCI and 28 days (range 12-94) in NO-TOCI group (HR = 0.56; 95% CI = 0.25-1.22, P = .19). Cumulative incidences of day 100 acute GvHD grades II-IV (P = .97) and grades III-IV (P = .47) were similar between the 2 groups. However, cumulative incidence of chronic GvHD at 1 year was significantly higher in patients receiving TOCI (64% versus 24%; P = .05). Rates of NRM (P = .66), relapse (P = .83), disease-free survival (P = .86), and overall survival (P = .73)