CAR-T Cell Therapy for ALL

Summary

Acute lymphoblastic leukemia (ALL) is the most common malignancy in children and the second most frequent acute leukemia in adults. B-cell ALL constitutes approximately 85% of all ALL diagnoses. In Pakistan, ALL represents the most prevalent haematological malignancy presenting to tertiary centres, with AFBMTC receiving the largest national referral volume for haematological malignancies and transplantation. First-line combination chemotherapy achieves complete remission (CR) in \>95% of paediatric patients; however, 15-20% relapse. Outcomes following first relapse are substantially inferior: second-line salvage chemotherapy achieves CR2 in 30-50% of patients, and long-term event-free survival (EFS) after conventional chemotherapy alone is \<10%. Outcomes in adult ALL are even more dismal, with OS at 5 years below 40% even in first CR without allogeneic transplant. Patients with primary refractory ALL or multiply relapsed ALL have an unmet medical need for novel therapeutic approaches. The classical paradigm of chemotherapy followed by allogeneic haematopoietic stem cell transplantation (allo-HSCT) is limited by donor availability, conditioning-related mortality, and inability to achieve remission before transplant.

Timeline

Start

2026-06-01

Primary completion

2027-12-31

Completion

2027-12-31

Publications

• Background . Sharma P, Srikantaiah V, Mitra S, et al. NexCAR19: indigenously developed anti-CD19 CAR-T in India - results from Phase I/II study. Indian J Hematol Blood Transfus. 2023 [LMIC reference].
• Background Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, Braunschweig I, Oluwole OO, Siddiqi T, Lin Y, Timmerman JM, Stiff PJ, Friedberg JW, Flinn IW, Goy A, Hill BT, Smith MR, Deol A, Farooq U, McSweeney P, Munoz J, Avivi I, Castro JE, Westin JR, Chavez JC, Ghobadi A, Komanduri KV, Levy R, Jacobsen ED, Witzig TE, Reagan P, Bot A, Rossi J, Navale L, Jiang Y, Aycock J, Elias M, Chang D, Wiezorek J, Go WY. Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma. N Engl J Med. 2017 Dec 28;377(26):2531-2544. doi: 10.1056/NEJMoa1707447. Epub 2017 Dec 10.
• Background Grupp SA, Kalos M, Barrett D, Aplenc R, Porter DL, Rheingold SR, Teachey DT, Chew A, Hauck B, Wright JF, Milone MC, Levine BL, June CH. Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N Engl J Med. 2013 Apr 18;368(16):1509-1518. doi: 10.1056/NEJMoa1215134. Epub 2013 Mar 25.
• Background Hay KA, Hanafi LA, Li D, Gust J, Liles WC, Wurfel MM, Lopez JA, Chen J, Chung D, Harju-Baker S, Cherian S, Chen X, Riddell SR, Maloney DG, Turtle CJ. Kinetics and biomarkers of severe cytokine release syndrome after CD19 chimeric antigen receptor-modified T-cell therapy. Blood. 2017 Nov 23;130(21):2295-2306. doi: 10.1182/blood-2017-06-793141. Epub 2017 Sep 18.
• Background Lee DW, Santomasso BD, Locke FL, Ghobadi A, Turtle CJ, Brudno JN, Maus MV, Park JH, Mead E, Pavletic S, Go WY, Eldjerou L, Gardner RA, Frey N, Curran KJ, Peggs K, Pasquini M, DiPersio JF, van den Brink MRM, Komanduri KV, Grupp SA, Neelapu SS. ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells. Biol Blood Marrow Transplant. 2019 Apr;25(4):625-638. doi: 10.1016/j.bbmt.2018.12.758. Epub 2018 Dec 25.
• Background 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 ER, 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. Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia. N Engl J Med. 2018 Feb 1;378(5):439-448. doi: 10.1056/NEJMoa1709866.

Drugs

Indications