Cellular therapy conditioning regimens

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Section editor
Talal Hilal, MD
Mayo Clinic
Phoenix, AZ, USA

Unlike most other regimen pages, this one is not disease-specific. Rather, this is a gathering point for all CAR T-cel and other immune effector cell (IEC) conditioning regimens. Following the conventions of allogeneic transplant, unless otherwise specified, the day before cell infusion is day -1, the day of cell infusion is day 0, and the day after cell infusion is day +1.
These links will take you to highly related pages:

3 regimens on this page
5 variants on this page


Low-dose conditioning regimens for cellular therapy, all lines of therapy

Bendamustine monotherapy

Regimen

Study Evidence
Schuster et al. 2018 (JULIET) Phase 2

Note: Lymphodepleting chemotherapy may be omitted if a patient’s white blood cell count is less than or equal to 1 x 109/L within 1 week prior to tisagenlecleucel infusion. This regimen is suggested if a patient experienced a previous grade 4 hemorrhagic cystitis with cyclophosphamide or demonstrates resistance to a previous cyclophosphamide-containing regimen.

Chemotherapy

References

  1. JULIET: Schuster SJ, Bishop MR, Tam CS, Waller EK, Borchmann P, McGuirk JP, Jäger U, Jaglowski S, Andreadis C, Westin JR, Fleury I, Bachanova V, Foley SR, Ho PJ, Mielke S, Magenau JM, Holte H, Pantano S, Pacaud LB, Awasthi R, Chu J, Anak Ö, Salles G, Maziarz RT; JULIET Investigators. Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma. N Engl J Med. 2019 Jan 3;380(1):45-56. Epub 2018 Dec 1. link to original article PubMed NCT02445248
    1. Update: Schuster SJ, Tam CS, Borchmann P, Worel N, McGuirk JP, Holte H, Waller EK, Jaglowski S, Bishop MR, Damon LE, Foley SR, Westin JR, Fleury I, Ho PJ, Mielke S, Teshima T, Janakiram M, Hsu JM, Izutsu K, Kersten MJ, Ghosh M, Wagner-Johnston N, Kato K, Corradini P, Martinez-Prieto M, Han X, Tiwari R, Salles G, Maziarz RT. Long-term clinical outcomes of tisagenlecleucel in patients with relapsed or refractory aggressive B-cell lymphomas (JULIET): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol. 2021 Oct;22(10):1403-1415. Epub 2021 Sep 10. link to original article PubMed

Cytarabine & Etoposide (CYVE)

CYVE: CYtarabine & VEpeside (Etoposide)

Regimen

Study Dates of enrollment Evidence
Maude et al. 2018 (ELIANA) 2015-2017 Phase 2

Note: This regimen is intended for patients with a history of grade 4 hemorrhagic cystitis from cyclophosphamide, or chemorefractory disease in the context of cyclophosphamide. CAR-T cells are to be given 2 to 14 days after completion of lymphodepleting therapy.

Chemotherapy

References

  1. ELIANA: 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. link to original article link to supplementary protocol contains dosing details in supplement link to PMC article PubMed NCT02435849

Cyclophosphamide & Fludarabine (FC)

FC: Fludarabine & Cyclophosphamide

Regimen variant #1, 25/250

Study Evidence
Schuster et al. 2018 (JULIET) Phase 2

Note: Lymphodepleting chemotherapy may be omitted if a patient’s white blood cell count is less than or equal to 1 x 109/L within 1 week prior to tisagenlecleucel infusion.

Chemotherapy

Subsequent treatment

  • Infuse tisagenlecleucel 2 to 11 days after completion of the lymphodepleting chemotherapy


Regimen variant #2, 30/500, 2 doses of cyclophosphamide, 4 doses of fludarabine

Study Dates of enrollment Evidence
Maude et al. 2018 (ELIANA) 2015-2017 Phase 2

Note: CAR-T cells are to be given 2 to 14 days after completion of lymphodepleting therapy.

Chemotherapy


Regimen variant #3, 30/500, 3 doses of cyclophosphamide, 3 doses of fludarabine

Study Evidence
Locke et al. 2017 (ZUMA-1) Phase 1/2

Chemotherapy

References

  1. ZUMA-1: Locke FL, Neelapu SS, Bartlett NL, Siddiqi T, Chavez JC, Hosing CM, Ghobadi A, Budde LE, Bot A, Rossi JM, Jiang Y, Xue AX, Elias M, Aycock J, Wiezorek J, Go WY. Phase 1 results of ZUMA-1: A multicenter study of KTE-C19 anti-CD19 CAR T cell therapy in refractory aggressive lymphoma. Mol Ther. 2017 Jan 4;25(1):285-295. Epub 2017 Jan 4. link to original article link to PMC article contains dosing details in manuscript PubMed NCT02348216
    1. Update: 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. Epub 2017 Dec 10. link to original article contains dosing details in manuscript link to PMC article PubMed
    2. Update: Locke FL, Ghobadi A, Jacobson CA, Miklos DB, Lekakis LJ, Oluwole OO, Lin Y, Braunschweig I, Hill BT, Timmerman JM, Deol A, Reagan PM, Stiff P, Flinn IW, Farooq U, Goy A, McSweeney PA, Munoz J, Siddiqi T, Chavez JC, Herrera AF, Bartlett NL, Wiezorek JS, Navale L, Xue A, Jiang Y, Bot A, Rossi JM, Kim JJ, Go WY, Neelapu SS. Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1-2 trial. Lancet Oncol. 2019 Jan;20(1):31-42. Epub 2018 Dec 2. link to original article link to PMC article contains dosing details in manuscript PubMed
  2. ELIANA: 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. link to original article link to supplementary protocol contains dosing details in supplement link to PMC article PubMed NCT02435849
  3. JULIET: Schuster SJ, Bishop MR, Tam CS, Waller EK, Borchmann P, McGuirk JP, Jäger U, Jaglowski S, Andreadis C, Westin JR, Fleury I, Bachanova V, Foley SR, Ho PJ, Mielke S, Magenau JM, Holte H, Pantano S, Pacaud LB, Awasthi R, Chu J, Anak Ö, Salles G, Maziarz RT; JULIET Investigators. Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma. N Engl J Med. 2019 Jan 3;380(1):45-56. Epub 2018 Dec 1. link to original article PubMed NCT02445248
    1. Update: Schuster SJ, Tam CS, Borchmann P, Worel N, McGuirk JP, Holte H, Waller EK, Jaglowski S, Bishop MR, Damon LE, Foley SR, Westin JR, Fleury I, Ho PJ, Mielke S, Teshima T, Janakiram M, Hsu JM, Izutsu K, Kersten MJ, Ghosh M, Wagner-Johnston N, Kato K, Corradini P, Martinez-Prieto M, Han X, Tiwari R, Salles G, Maziarz RT. Long-term clinical outcomes of tisagenlecleucel in patients with relapsed or refractory aggressive B-cell lymphomas (JULIET): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol. 2021 Oct;22(10):1403-1415. Epub 2021 Sep 10. link to original article PubMed