Late Non-Relapse Mortality (NRM) after Standard-of-Care (SOC) CAR-T Cell Therapy for Large B-Cell Lymphoma (LBCL): Frequency, Causes, and Risk Factors.a GLA/DRST Real World Analysis

• Published in: Blood 2021-11, Vol.138 (Supplement 1), p.1748-1748
• Main Authors: Dreger, Peter, Schubert, Maria-Luisa, Holtick, Udo, Subklewe, Marion, Bastian, von Tresckow, Ayuk, Francis A., Wagner, Eva Maria, Wulf, Gerald, Marks, Reinhard, Penack, Olaf, Schnetzke, Ulf, Koenecke, Christian, Von Bonin, Malte, Stelljes, Matthias, Glass, Bertram, Baldus, Claudia D., Vucinic, Vladan, Mougiakakos, Dimitrios, Topp, Max, Wolff, Daniel, Schroers, Roland, Borchmann, Peter, Rejeski, Kai, Hanoun, Christine, Lengerke, Claudia, Thomas, Simone, Beelen, Dietrich W., Kröger, Nicolaus, Bethge, Wolfgang A
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2021-151469

Introduction Although the labeled CD19 targeting CAR-T cell constructs axi-cel and tisa-cel are generally associated with an acceptable safety profile, non-relapse deaths can occur. Little is known about timing, causes and predictors of NRM following SOC CAR-T cell therapy for LBCL. Here, we analyzed frequency, causes, and risk factors of non-relapse deaths with focus on late NRM (beyond 4 weeks after dosing) using registry data provided by the DRST, the national partner of the EBMT. Methods Patients were selected from 356 consecutive patients who received SOC CAR-T treatment of LBCL between November 2018 and April 2021 at 21 German centers and were registered with the DRST/EBMT. Baseline patient, disease, and transplant data were collected from MED-A cellular therapy forms. Centers were contacted to provide additional treatment and follow-up information. Patients with late NRM (defined as NRM occurring beyond 4 weeks after dosing without prior LBCL relapse or progression) were compared with all patients surviving progression-free the 4-week landmark after dosing without subsequent NRM. Cumulative incidences of NRM were calculated considering relapse/progression as competing event. Results The analysis set consisted of 312 patients surviving progression-free at least 28 days after CAR-T treatment and remained alive until the end of follow-up or had a documented cause of death. Median age was 61 years (19-83), 66% were male, 52% had an IPI ≥3, 13 had an ECOG score >1, 70% had received ≥3 treatment lines, 33% had failed a prior HCT, and 78% were refractory at lymphodepletion. 50% had been treated at a center contributing ≥20 cases with axi-cel (52%) or tisa-cel (48%). Grade ≥3 CRS and grade ≥3 neurotoxicity (NT) had occurred in 11% each, and 7% had no neutrophil recovery at day 100 post dosing or at last follow-up, whatever was earlier. With a median follow-up of 11.2 months, 124 patients (40%) had died, 109 (35%) LBCL-related, and 15 (5%) because of NRM. The cumulative incidence of late NRM at 12 months post dosing was 4.3% (95%CI 2.0-6.6). Causes of NRM were infections in 10 patients (bacterial or fungal sepsis/pneumonia 6; viral/atypical pneumonia/encephalitis 4); late NT 2; hyperinflammatory syndrome 1; 2 nd malignancy 1; unknown 1). Of note, 5 of the 6 lethal fungal/bacterial infections occurred subsequent to high grade NT. There was no significant difference between patients experiencing and not experiencing NRM in terms of age, gender, IPI, ECOG, pret