Peri-CAR-T practice patterns and survival predictors for all CAR-T patients and post-CAR-T failure in aggressive B-NHL.
Joanna C ZurkoImran NizamuddinNarendranath EpperlaKevin A DavidJonathon B CohenTamara MoyoThomas A OllilaBrian T HessIshan RoyRobert FerdmanJieqi LiuSayan Mullick ChowdhuryJason T RomancikRahul S BhansaliElyse I HarrisMckenzie SorrellRebecca MaselAdam S KittaiNathan DenlingerAudrey M SigmundLindsey A FitzgeraldCarlos GalvezShuo MaJane N WinterBarbara ProLeo I GordonAlexey V DanilovDeborah M StephensNirav N ShahVaishalee P KenkreStefan K BartaPallawi TorkaGeoffrey ShouseReem KarmaliPublished in: Blood advances (2022)
Most patients receiving CAR T-cell therapy (CAR-T) for aggressive B-cell lymphoma (B-NHL) will not experience a durable remission. There are several novel agents approved for the treatment relapsed, refractory aggressive B-NHL; however, it remains unclear how to sequence these therapies pre- and post-CAR-T (peri-CAR-T). We conducted a multicenter retrospective analysis for the purpose of describing peri-CAR-T practice patterns and survival predictors for patients receiving CD19-directed CAR-T. Patients (n=514) from thirteen centers treated with CAR-T for aggressive B-NHL between 2015-2021 were included. Clinical characteristics, CAR-T outcomes and treatment regimens administered pre- and post-CAR-T were collected. Survival curves were constructed using Kaplan Meier method. Multivariate Cox regression was used to determine the impact of variables on survival outcomes. For all patients receiving CAR-T, a greater number lines of therapy prior to CAR-T apheresis and receipt of bridging therapy were predictive of inferior progression-free survival (PFS) and overall survival (OS). From time of CAR-T infusion, median PFS and OS were 7.6 and 25.6 months (n=514). From time of progression post-CAR-T (n=254), median OS was 5.5 months. The median PFS of treatments given in the first-line post-CAR-T failure (n=167) was just 2.8 months. Patients with refractory disease at day 30 had inferior OS and were less likely to receive subsequent treatment(s) compared to other patients with CAR-T failure. AlloHCT for select patients at any time following CAR-T failure (n=16) led to durable responses in over half at one-year. These data provide a benchmark for future clinical trials in patients with progression post-CAR-T, an unmet clinical need.
Keyphrases
- free survival
- cell therapy
- end stage renal disease
- ejection fraction
- clinical trial
- newly diagnosed
- chronic kidney disease
- stem cells
- peritoneal dialysis
- acute lymphoblastic leukemia
- metabolic syndrome
- low dose
- acute myeloid leukemia
- machine learning
- systemic lupus erythematosus
- skeletal muscle
- type diabetes
- artificial intelligence
- replacement therapy
- patient reported
- study protocol
- ulcerative colitis