Patterns of leukocyte recovery predict infectious complications after CD19 CAR-T cell therapy in a real-world setting

Astha Thakkar, Zhu Cui, Stephen Zachary Peeke, Nishi Shah, Kith Pradhan, Amanda Lombardo, Fariha Khatun, Jennat Mustafa, Alyssa de Castro, Kailyn Gillick, Felisha Joseph, Anjali Naik, Shafia Rahman, Angelica D'Aiello, Richard Elkind, Susan Sakalian, Karen Fehn, Karen Wright, Michelly Abreu, Latoya Townsend-NugentNicole Chambers, Rosmi Mathew, Donika Binakaj, Randin Nelson, Carlo Palesi, Monika Paroder, Joan Uehlinger, Yanhua Wang, Yang Shi, Xingxing Zang, Hao Wang, Christopher Nishimura, Xiaoxin Ren, Ulrich G. Steidl, Kira Gritsman, Murali Janakiram, Noah Kornblum, Olga Derman, Ioannis Mantzaris, Aditi Shastri, Rachel Bartash, Yoram Puius, Margaret McCort, Mendel Goldfinger, Lizamarie Bachier-Rodriguez, Amit Verma, Ira Braunschweig, R. Alejandro Sica

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Background: Adoptive immunotherapy using CD19-targeted Chimeric antigen receptor T cells (CAR-T) has revolutionized the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Data is limited on the propensity of infections and lymphohematopoietic reconstitution after Day 30 (D30) following CAR-T cell therapy. In this study, we evaluated the prevalence and nature of infectious complications in an expanded cohort of DLBCL patients treated with CD19 CAR-T therapy and its association with the dynamics of leukocyte subpopulation reconstitution post-CAR-T cell therapy. Methods: We conducted a retrospective study including 19 patients who received axicabtagene ciloleucel and investigated associations between cytopenia and infectious complications after D30. Results: Nineteen patients were included, consisting of 42% Hispanic, 32% Caucasian, 21% African-American, and 5% Asian subjects. Post-D30 of CAR-T infusion, 47% patients (n=9) developed an infection and 53% (n=10) remained infection-free. The most common infection type observed was viral (7 patients) followed by bacterial (5 patients) and fungal (3 patients). Of 25 total infectious events, 56% were grade 1 or 2 and 44% were grade 3 with 10 being viral in etiology. To determine the kinetics of lymphohematopoietic reconstitution and its association with infection risk, we evaluated the relationship between cytopenias and rates of infection after D30. Notably, compared to non-infection group, infection group had a higher median absolute lymphocyte count (ALC) (1,000/µL vs. 600/µL, P<0.05), a lower median absolute neutrophil count (ANC)/ALC ratio (1.6 vs. 3.1, P<0.05) and a lower median AMC/ALC at D30 (0.37 vs. 1.67, P<0.05). In addition, we observed that only 22% of patients had recovered ANC >1,500/µL in the infection group as opposed to 70% in the non-infection group at D90 (P<0.05). Fifty-eight percent of the patients (11/19) with relapsed refractory DLBCL achieved a complete response with a median follow-up of 233 days (7.7 months). Conclusions: Although CAR-T cell therapy is highly effective, infectious complications remain an important cause of morbidity and mortality. Low ANC/ALC and AMC/ALC ratios at D30 are potential novel predictors of infection and can be considered in future prophylactic strategies.

Original languageEnglish (US)
Article number18
JournalStem Cell Investigation
Volume8
DOIs
StatePublished - Sep 2021

Keywords

  • Axicabtagene ciloleucel
  • Chimeric antigen receptor T cell (CAR-T) CD19 cells
  • Infection
  • Real-world cohort
  • Relapsed/refractory diffuse large B-cell lymphoma (DLBCL)

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Developmental Biology
  • Cell Biology

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