Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia

S. L. Maude, T. W. Laetsch, J. Buechner, S. Rives, M. Boyer, H. Bittencourt, P. Bader, M. R. Verneris, H. E. Stefanski, G. D. Myers, M. Qayed, B. De Moerloose, H. Hiramatsu, Krysta Schlis, K. L. Davis, P. L. Martin, Eneida Nemecek, G. A. Yanik, C. Peters, A. BaruchelN. Boissel, F. Mechinaud, A. Balduzzi, J. Krueger, C. H. June, B. L. Levine, P. Wood, T. Taran, M. Leung, K. T. Mueller, Y. Zhang, K. Sen, D. Lebwohl, M. A. Pulsipher, S. A. Grupp

Research output: Contribution to journalArticle

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Abstract

BACKGROUND In a single-center phase 1-2a study, the anti-CD19 chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel produced high rates of complete remission and was associated with serious but mainly reversible toxic effects in children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL). METHODS We conducted a phase 2, single-cohort, 25-center, global study of tisagenlecleucel in pediatric and young adult patients with CD19+ relapsed or refractory B-cell ALL. The primary end point was the overall remission rate (the rate of complete remission or complete remission with incomplete hematologic recovery) within 3 months. RESULTS For this planned analysis, 75 patients received an infusion of tisagenlecleucel and could be evaluated for efficacy. The overall remission rate within 3 months was 81%, with all patients who had a response to treatment found to be negative for minimal residual disease, as assessed by means of flow cytometry. The rates of event-free survival and overall survival were 73% (95% confidence interval [CI], 60 to 82) and 90% (95% CI, 81 to 95), respectively, at 6 months and 50% (95% CI, 35 to 64) and 76% (95% CI, 63 to 86) at 12 months. The median duration of remission was not reached. Persistence of tisagenlecleucel in the blood was observed for as long as 20 months. Grade 3 or 4 adverse events that were suspected to be related to tisagenlecleucel occurred in 73% of patients. The cytokine release syndrome occurred in 77% of patients, 48% of whom received tocilizumab. Neurologic events occurred in 40% of patients and were managed with supportive care, and no cerebral edema was reported. CONCLUSIONS In this global study of CAR T-cell therapy, a single infusion of tisagenlecleucel provided durable remission with long-term persistence in pediatric and young adult patients with relapsed or refractory B-cell ALL, with transient high-grade toxic effects.

Original languageEnglish (US)
Pages (from-to)439-448
Number of pages10
JournalNew England Journal of Medicine
Volume378
Issue number5
DOIs
StatePublished - Feb 1 2018

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B-Cell Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Young Adult
Confidence Intervals
Antigen Receptors
B-Lymphocytes
Poisons
Cell- and Tissue-Based Therapy
CD19 Antigens
Pediatrics
Brain Edema
Residual Neoplasm
Nervous System
Disease-Free Survival
Flow Cytometry
Cytokines
T-Lymphocytes
Survival

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Maude, S. L., Laetsch, T. W., Buechner, J., Rives, S., Boyer, M., Bittencourt, H., ... Grupp, S. A. (2018). Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. New England Journal of Medicine, 378(5), 439-448. https://doi.org/10.1056/NEJMoa1709866

Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. / Maude, S. L.; Laetsch, T. W.; Buechner, J.; Rives, S.; Boyer, M.; Bittencourt, H.; Bader, P.; Verneris, M. R.; Stefanski, H. E.; Myers, G. D.; Qayed, M.; De Moerloose, B.; Hiramatsu, H.; Schlis, Krysta; Davis, K. L.; Martin, P. L.; Nemecek, Eneida; Yanik, G. A.; Peters, C.; Baruchel, A.; Boissel, N.; Mechinaud, F.; Balduzzi, A.; Krueger, J.; June, C. H.; Levine, B. L.; Wood, P.; Taran, T.; Leung, M.; Mueller, K. T.; Zhang, Y.; Sen, K.; Lebwohl, D.; Pulsipher, M. A.; Grupp, S. A.

In: New England Journal of Medicine, Vol. 378, No. 5, 01.02.2018, p. 439-448.

Research output: Contribution to journalArticle

Maude, SL, Laetsch, TW, Buechner, J, Rives, S, Boyer, M, Bittencourt, H, Bader, P, Verneris, MR, Stefanski, HE, Myers, GD, Qayed, M, De Moerloose, B, Hiramatsu, H, Schlis, K, Davis, KL, Martin, PL, Nemecek, E, Yanik, GA, Peters, C, Baruchel, A, Boissel, N, Mechinaud, F, Balduzzi, A, Krueger, J, June, CH, Levine, BL, Wood, P, Taran, T, Leung, M, Mueller, KT, Zhang, Y, Sen, K, Lebwohl, D, Pulsipher, MA & Grupp, SA 2018, 'Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia', New England Journal of Medicine, vol. 378, no. 5, pp. 439-448. https://doi.org/10.1056/NEJMoa1709866
Maude SL, Laetsch TW, Buechner J, Rives S, Boyer M, Bittencourt H et al. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. New England Journal of Medicine. 2018 Feb 1;378(5):439-448. https://doi.org/10.1056/NEJMoa1709866
Maude, S. L. ; Laetsch, T. W. ; Buechner, J. ; Rives, S. ; Boyer, M. ; Bittencourt, H. ; Bader, P. ; Verneris, M. R. ; Stefanski, H. E. ; Myers, G. D. ; Qayed, M. ; De Moerloose, B. ; Hiramatsu, H. ; Schlis, Krysta ; Davis, K. L. ; Martin, P. L. ; Nemecek, Eneida ; Yanik, G. A. ; Peters, C. ; Baruchel, A. ; Boissel, N. ; Mechinaud, F. ; Balduzzi, A. ; Krueger, J. ; June, C. H. ; Levine, B. L. ; Wood, P. ; Taran, T. ; Leung, M. ; Mueller, K. T. ; Zhang, Y. ; Sen, K. ; Lebwohl, D. ; Pulsipher, M. A. ; Grupp, S. A. / Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. In: New England Journal of Medicine. 2018 ; Vol. 378, No. 5. pp. 439-448.
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abstract = "BACKGROUND In a single-center phase 1-2a study, the anti-CD19 chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel produced high rates of complete remission and was associated with serious but mainly reversible toxic effects in children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL). METHODS We conducted a phase 2, single-cohort, 25-center, global study of tisagenlecleucel in pediatric and young adult patients with CD19+ relapsed or refractory B-cell ALL. The primary end point was the overall remission rate (the rate of complete remission or complete remission with incomplete hematologic recovery) within 3 months. RESULTS For this planned analysis, 75 patients received an infusion of tisagenlecleucel and could be evaluated for efficacy. The overall remission rate within 3 months was 81{\%}, with all patients who had a response to treatment found to be negative for minimal residual disease, as assessed by means of flow cytometry. The rates of event-free survival and overall survival were 73{\%} (95{\%} confidence interval [CI], 60 to 82) and 90{\%} (95{\%} CI, 81 to 95), respectively, at 6 months and 50{\%} (95{\%} CI, 35 to 64) and 76{\%} (95{\%} CI, 63 to 86) at 12 months. The median duration of remission was not reached. Persistence of tisagenlecleucel in the blood was observed for as long as 20 months. Grade 3 or 4 adverse events that were suspected to be related to tisagenlecleucel occurred in 73{\%} of patients. The cytokine release syndrome occurred in 77{\%} of patients, 48{\%} of whom received tocilizumab. Neurologic events occurred in 40{\%} of patients and were managed with supportive care, and no cerebral edema was reported. CONCLUSIONS In this global study of CAR T-cell therapy, a single infusion of tisagenlecleucel provided durable remission with long-term persistence in pediatric and young adult patients with relapsed or refractory B-cell ALL, with transient high-grade toxic effects.",
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TY - JOUR

T1 - Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia

AU - Maude, S. L.

AU - Laetsch, T. W.

AU - Buechner, J.

AU - Rives, S.

AU - Boyer, M.

AU - Bittencourt, H.

AU - Bader, P.

AU - Verneris, M. R.

AU - Stefanski, H. E.

AU - Myers, G. D.

AU - Qayed, M.

AU - De Moerloose, B.

AU - Hiramatsu, H.

AU - Schlis, Krysta

AU - Davis, K. L.

AU - Martin, P. L.

AU - Nemecek, Eneida

AU - Yanik, G. A.

AU - Peters, C.

AU - Baruchel, A.

AU - Boissel, N.

AU - Mechinaud, F.

AU - Balduzzi, A.

AU - Krueger, J.

AU - June, C. H.

AU - Levine, B. L.

AU - Wood, P.

AU - Taran, T.

AU - Leung, M.

AU - Mueller, K. T.

AU - Zhang, Y.

AU - Sen, K.

AU - Lebwohl, D.

AU - Pulsipher, M. A.

AU - Grupp, S. A.

PY - 2018/2/1

Y1 - 2018/2/1

N2 - BACKGROUND In a single-center phase 1-2a study, the anti-CD19 chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel produced high rates of complete remission and was associated with serious but mainly reversible toxic effects in children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL). METHODS We conducted a phase 2, single-cohort, 25-center, global study of tisagenlecleucel in pediatric and young adult patients with CD19+ relapsed or refractory B-cell ALL. The primary end point was the overall remission rate (the rate of complete remission or complete remission with incomplete hematologic recovery) within 3 months. RESULTS For this planned analysis, 75 patients received an infusion of tisagenlecleucel and could be evaluated for efficacy. The overall remission rate within 3 months was 81%, with all patients who had a response to treatment found to be negative for minimal residual disease, as assessed by means of flow cytometry. The rates of event-free survival and overall survival were 73% (95% confidence interval [CI], 60 to 82) and 90% (95% CI, 81 to 95), respectively, at 6 months and 50% (95% CI, 35 to 64) and 76% (95% CI, 63 to 86) at 12 months. The median duration of remission was not reached. Persistence of tisagenlecleucel in the blood was observed for as long as 20 months. Grade 3 or 4 adverse events that were suspected to be related to tisagenlecleucel occurred in 73% of patients. The cytokine release syndrome occurred in 77% of patients, 48% of whom received tocilizumab. Neurologic events occurred in 40% of patients and were managed with supportive care, and no cerebral edema was reported. CONCLUSIONS In this global study of CAR T-cell therapy, a single infusion of tisagenlecleucel provided durable remission with long-term persistence in pediatric and young adult patients with relapsed or refractory B-cell ALL, with transient high-grade toxic effects.

AB - BACKGROUND In a single-center phase 1-2a study, the anti-CD19 chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel produced high rates of complete remission and was associated with serious but mainly reversible toxic effects in children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL). METHODS We conducted a phase 2, single-cohort, 25-center, global study of tisagenlecleucel in pediatric and young adult patients with CD19+ relapsed or refractory B-cell ALL. The primary end point was the overall remission rate (the rate of complete remission or complete remission with incomplete hematologic recovery) within 3 months. RESULTS For this planned analysis, 75 patients received an infusion of tisagenlecleucel and could be evaluated for efficacy. The overall remission rate within 3 months was 81%, with all patients who had a response to treatment found to be negative for minimal residual disease, as assessed by means of flow cytometry. The rates of event-free survival and overall survival were 73% (95% confidence interval [CI], 60 to 82) and 90% (95% CI, 81 to 95), respectively, at 6 months and 50% (95% CI, 35 to 64) and 76% (95% CI, 63 to 86) at 12 months. The median duration of remission was not reached. Persistence of tisagenlecleucel in the blood was observed for as long as 20 months. Grade 3 or 4 adverse events that were suspected to be related to tisagenlecleucel occurred in 73% of patients. The cytokine release syndrome occurred in 77% of patients, 48% of whom received tocilizumab. Neurologic events occurred in 40% of patients and were managed with supportive care, and no cerebral edema was reported. CONCLUSIONS In this global study of CAR T-cell therapy, a single infusion of tisagenlecleucel provided durable remission with long-term persistence in pediatric and young adult patients with relapsed or refractory B-cell ALL, with transient high-grade toxic effects.

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