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. 2025 Nov 11;9(21):5489-5500.
doi: 10.1182/bloodadvances.2025016149.

Real-world outcomes of infections following tisagenlecleucel in patients with B-cell ALL: a CIBMTR analysis

Hemalatha G Rangarajan  1 , Prakash Satwani  2 , Megan M Herr  3 , Min Chen  4 , Michael J Martens  4   5 , Kitsada Wudhikarn  6 , Samuel John  7 , Vanessa A Fabrizio  8 , Emily M Hsieh  9 , Amar H Kelkar  10 , Erin Doherty  11 , David I Marks  12 , Olle Ringden  13 , Brian Friend  14 , Matthew S Kelly  15 , Nosha Farhadfar  16 , Tim Prestidge  17 , Nasheed M Hossain  18 , Hongtao Liu  19 , Shahrukh Hashmi  20   21 , Dipenkumar Modi  22 , Lena E Winestone  23 , Zeinab El Boghdadly  24 , Hemant S Murthy  25 , Miguel-Angel Perales  26   27 , Roy F Chemaly  14 , Christopher E Dandoy  28 , Joshua A Hill  29   30 , Anna Huppler  4   31 , Marcie Riches  4 , Jeffery J Auletta  32   33
Affiliations

Real-world outcomes of infections following tisagenlecleucel in patients with B-cell ALL: a CIBMTR analysis

Hemalatha G Rangarajan et al. Blood Adv. .

Abstract

Tisagenlecleucel (tisa-cel) is a CD19-directed chimeric antigen receptor T-cell therapy for relapsed/refractory precursor B-cell acute lymphoblastic leukemia (R/R B-ALL). We report infectious complications for 100 days (D100) following tisa-cel therapy in 471 pediatric and young adults (median age 13.8 years) with R/R B-ALL reported from September 2017 to June 2022. By D100, 137 (29%) patients had an infectious event, with an infection density of 0.542 per 100 person-days at risk. D100 cumulative incidences of bacterial, viral, and fungal infections were 14.1%, 11.6%, and 1.3%, corresponding to infection density scores of 0.296, 0.213, and 0.033 per 100 person-days at risk, respectively. In a multivariable analysis, receipt of ≥3 lines of therapy before tisa-cel (hazard ratio [HR], 1.86; 95% confidence interval [CI], 1.13-3.08; P = .015), any-grade cytokine release syndrome (HR, 1.78; 95% CI, 1.17-2.71; P = .007), and lack of neutrophil recovery (HR, 2.63; 95% CI, 1.47-4.69; P = .001) were associated with an increased risk for any infection. Similar associations were observed for bacterial infections, with the addition of younger age as an adverse risk (<6 vs 6-15 years; HR, 2.38; 95% CI, 1.23-4.61; P = .01). Risk factors for viral infections included increasing age (1-year increase; HR, 1.05; 95% CI, 1.01-1.09; P = .016), prior history of any infection (HR, 2.76, 95% CI, 1.40-5.46; P = .004), and prior hematopoietic cell transplant (HR, 2.10; 95% CI, 1.18-3.71; P = .011). D100 infection-related mortality (IRM) rate was low at 0.2% (95% CI, 0.0-0.8). In this multicenter real-world study, we observed a high incidence of infectious complications but a low IRM following tisa-cel for R/R B-ALL.

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Conflict of interest statement

Conflict-of-interest disclosure: H.G.R. reports consultancy fees from Medexus and Vertex Therapeutics; and an honorary CD33CAR T medical monitor position with National Marrow Donor Program (NMDP). P.S. reports consultancy fees from Sobi. V.A.F. reports consultancy fees from Adaptimmune. E.M.H. reports consultancy fees from Novartis. M.S.K. reports consultancy fees and institutional research support from Merck. N.F. reports compensation from Incyte; advisory and speaker fees from Sanofi; consultancy for Omeros; medical monitor position with Bone Marrow Transplant Clinical Trials Network (BMT CTN); and data safety and monitoring board (DSMB) membership for Chronic Graft Versus Host Disease Consortium. H.L. served at the advisory board meeting for Rigel and Incyte; and received consultation fees from AbbVie in the past 24 months. D.M. reports consulting/advisory role for ADC therapeutics, Genmab, Genentech (spouse), Daiichi Sankyo (spouse), AstraZeneca (spouse); research funding for investigator initiated trials from Genentech, Genmab, Karyopharm, AstraZeneca (spouse); and expert testimony from AstraZeneca. H.S.M. reports compensation for advisory board/consultancy from CRISPR Therapeutics, Bristol Myers Squibb, Jazz, Incyte, Sobi, Autolus, Senti Bioscience; and medical monitor position for BMT CTN/NMDP. M.-A.P. reports honoraria from Adicet, Allogene, Caribou Biosciences, Celgene, Bristol Myers Squibb, Equilium, Exevir, ImmPACT Bio, Incyte, Karyopharm, Kite/Gilead, Merck, Miltenyi Biotec, MorphoSys, Nektar Therapeutics, Novartis, Omeros, OrcaBio, Sanofi, Syncopation, Takeda, VectivBio AG, and Vor Biopharma; serves on DSMBs for Cidara Therapeutics and Sellas Life Sciences; has ownership interests in Omeros and OrcaBio; and has received institutional research support for clinical trials from Allogene, Incyte, Kite/Gilead, Miltenyi Biotec, Nektar Therapeutics, and Novartis. R.F.C. reports compensation for advisory role for ADMA Biologics, Merck/MSD, Takeda, Shinogi, AiCuris, Astellas, Tether, Karius, Moderna, Pfizer, Invivyd, Gilead, AssemblyBio, Eurofins-Viracor, and Ansun Pharmaceuticals; and research support from Merck, Karius, AiCuris, Ansun Pharmaceuticals, Takeda, OM1, Genentech, and Eurofins-Viracor. C.E.D. reports compensation and honorarium from Omeros and Alexion Pharmaceuticals; and honorarium from Alexion for a presentation at European Society for Blood and Marrow Transplantation. J.A.H. reports consultancy for Moderna, Allovir, Gilead, Takeda, CSL Behring, Karius, Symbio, Geovax, and Sanofi; research funding from Gilead, Takeda, Merck, Geovax, and Sanofi; and significant payments from Takeda for advisory board meetings. A.H. reports honorarium from Elsevier for Clinical Overview Chapter. J.J.A. reports being part of the advisory committee for AscellaHealth. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Normalized infection density by organism and time of tisa-cel therapy for R/R B-ALL. Each figure is normalized for the specified nonoverlapping time period.
Figure 2.
Figure 2.
Cumulative incidence of infection with competing events following CD19 CAR T-cell therapy for R/R B-ALL. (A) Any infection; (B) bacterial infection; (C) viral infection; (D) fungal infection.
Figure 3.
Figure 3.
Cox model multivariable analysis of cause-specific hazard rate of infections during D0 to D30 after CAR T-cell therapy.
Figure 4.
Figure 4.
Cox model multivariable analysis of cause-specific hazard rate of infections during D0 to D100 after CAR T-cell therapy.
Figure 5.
Figure 5.
OS state probabilities within 1 year of CAR T-cell therapy.
See this image and copyright information in PMC

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