Chronic Myeloid Leukemia Treatment Regimens

Chronic Myeloid Leukemia Treatment Regimens

Clinical Trials: The NCCN recommends cancer patient participation in clinical trials as the gold standard for treatment.

Cancer therapy selection, dosing, administration, and the management of related adverse events can be a complex process that should be handled by an experienced healthcare team. Clinicians must choose and verify treatment options based on the individual patient; drug dose modifications and supportive care interventions should be administered accordingly. The cancer treatment regimens below may include both U.S. Food and Drug Administration-approved and unapproved indications/regimens. These regimens are provided only to supplement the latest treatment strategies.

These Guidelines are a work in progress that may be refined as often as new significant data becomes available. The NCCN Guidelines® are a consensus statement of its authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult any NCCN Guidelines® is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The National Comprehensive Cancer Network makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way.

Note: All recommendations are category 2A unless otherwise indicated.

▶Chronic Phase CML1,a

REGIMEN

DOSING

Primary Treatment for Low-risk Score1

Preferred Regimens

Bosutinib
(Category 1)2-7

Days 1-28: Bosutinib 400mg orally once daily.

Repeat cycle every 4 weeks.

Dasatinib
(Category 1)7-11

Days 1-28: Dasatinib 100mg orally once daily.

Repeat cycle every 4 weeks.

Imatinib
(Category 1)7,12-16

Days 1-28: Imatinib 400mg orally once daily.

Repeat cycle every 4 weeks.

Nilotinib
(Category 1)7,17-21

Days 1-28: Nilotinib 300mg orally twice daily.

Repeat cycle every 4 weeks.

Primary Treatment for Intermediate- or High-risk Score

Preferred Regimens

Bosutinib

(Category 1)2-7

Days 1-28: Bosutinib 400mg orally once daily.

Repeat cycle every 4 weeks.

Dasatinib

(Category 1)7-11

Days 1-28: Dasatinib 100mg orally once daily.

Repeat cycle every 4 weeks.

Nilotinib

(Category 1)7,17-21

Days 1-28: Nilotinib 300mg orally twice daily.

Repeat cycle every 4 weeks.

Other Recommended Regimens

Imatinib7,12-16

Days 1-28: Imatinib 400mg orally once daily.

Repeat cycle every 4 weeks.

Second-line and Subsequent TKI Therapy

Asciminib22-25

Resistant and/or intolerant to ≥2 TKIs

Days 1-28: Asciminib 80 mg orally once daily.

Repeat cycle every 4 weeks.

OR

Days 1-28: Asciminib 40mg orally every 12 hours.

Repeat cycle every 4 weeks.

T315I mutation

Days 1-28: Asciminib 200mg orally every 12 hours.

Repeat cycle every 4 weeks.

Bosutinib2-7

Days 1-28: Bosutinib 500mg orally once daily.

Repeat cycle every 4 weeks.

Dasatinib7-11

Days 1-28: Dasatinib 100mg orally once daily.

Repeat cycle every 4 weeks.

Imatinib7,12-16

Days 1-28: Imatinib 400-600mg orally once daily.

Repeat cycle every 4 weeks.

OR

Days 1-28: Imatinib 400mg orally twice daily.

Repeat cycle every 4 weeks.

Nilotinib7,17-21

Days 1-28: Nilotinib 400mg orally twice daily.

Repeat cycle every 4 weeks.

Omacetaxine26-28
(Resistant and/or intolerant to ≥2 TKIs)

Induction

Days 1-14: Omacetaxine 1.25mg/m2 subcutaneously twice daily.

Repeat cycle every 4 weeks until hematologic response, followed by maintenance therapy with:

Days 1-7: Omacetaxine 1.25mg/m2 subcutaneously twice daily.

Repeat cycle every 4 weeks.

Ponatinib29-31
(2 prior TKIs; T315I mutation; TKI intolerant/refractory)

Days 1-28: Ponatinib 45mg orally once daily.

Repeat cycle every 4 weeks, conditionally followed by (after achievement of BCR-ABL1 (IS) <1%):

Days 1-28: Ponatinib 15mg orally once daily.

Repeat cycle every 4 weeks.

▶Advanced Phase CML1,a

Treatment for Accelerated Phase1

Preferred Regimens

Bosutinib2-7

Days 1-28: Bosutinib 500mg orally once daily.

Repeat cycle every 4 weeks.

Dasatinib7-11

Days 1-28: Dasatinib 140mg orally once daily.

Repeat cycle every 4 weeks.

Nilotinib7,17-21

Days 1-28: Nilotinib 400mg orally twice daily.

Repeat cycle every 4 weeks.

Ponatinib7,29-31
(T315I mutation; other TKIs not indicated)

Days 1-28: Ponatinib 45mg orally once daily.

Repeat cycle every 4 weeks, conditionally followed by (after achievement of BCR-ABL1 (IS) <1%):

Days 1-28: Ponatinib 15mg orally once daily.

Repeat cycle every 4 weeks.

Other Recommended Regimens

Imatinib7,12-16,b

Days 1-28: Imatinib 600mg orally daily.

Repeat cycle every 4 weeks.

Useful in Certain Circumstances

Omacetaxine26-28
(Progression to accelerated phase only; resistant and/or intolerant to ≥2 TKIs)

Induction

Days 1-14: Omacetaxine 1.25mg/m2 subcutaneously twice daily.

Repeat cycle every 4 weeks until hematologic response, followed by maintenance therapy with:

Days 1-7: Omacetaxine 1.25mg/m2 subcutaneously twice daily.

Repeat cycle every 4 weeks.

Treatment for Blast Phase

Preferred Regimens

Bosutinib2-7

Days 1-28: Bosutinib 500mg orally once daily.

Repeat cycle every 4 weeks.

Dasatinib7-11

Days 1-28: Dasatinib 140mg orally once daily.

Repeat cycle every 4 weeks.

Imatinib7,12-16

Days 1-28: Imatinib 600mg orally daily.

Repeat cycle every 4 weeks.

Nilotinib7,17-21

Days 1-28: Nilotinib 400mg orally twice daily.

Repeat cycle every 4 weeks.

Ponatinib7,29-31
(T315I mutation; other TKIs not indicated)

Days 1-28: Ponatinib 45mg orally once daily.

Repeat cycle every 4 weeks, conditionally followed by (after achievement of BCR-ABL1 (IS) <1%):

Days 1-28: Ponatinib 15mg orally once daily.

Repeat cycle every 4 weeks.

a  CML, chronic myeloid leukemia; TKI, tyrosine kinase inhibitor.

b  Imatinib is not recommended for patients with disease progression on prior TKI therapy.

References

 1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Chromic Myeloid Leukemia V.3.2022. Available at: http://www.nccn.org/professionals/physician_gls/pdf/cml.pdf. Accessed January 30, 2022.

 2. Bosutinib (Bosulif) [package insert]. New York, NY: Pfizer; May 2021.

 3. Cortes JE, Gambacorti-Passerini C, Deininger MW, et al. Bosutinib versus imatinib for newly diagnosed chronic myeloid leukemia: Results from the randomized BFORE trial. J Clin Oncol. 2018;36(3):231-237.

 4. Cortes JE, Khoury HJ, Kantarjian HM, et al. Long-term bosutinib for chronic phase chronic myeloid leukemia after failure of imatinib plus dasatinib and/or nilotinib. Am J Hematol. 2016;91(12):1206-1214.

 5. Gambacorti-Passerini C, Cortes JE, Lipton JH, et al. Safety and efficacy of second-line bosutinib for chronic phase chronic myeloid leukemia over a five-year period: final results of a phase I/II study. Haematologica. 2018;103(8):1298-1307.

 6. García-Gutiérrez V, Milojkovic D, Hernandez-Boluda JC, et al. Safety and efficacy of bosutinib in fourth-line therapy of chronic myeloid leukemia patients. Ann Hematol. 2019;98(2):321-330.

 7. DeFilipp Z, Langston AA, Chen Z, et al. Does Post-transplant maintenance therapy with tyrosine kinase inhibitors improve outcomes of patients with high-risk Philadelphia chromosome-positive leukemia? Clin Lymphoma Myeloma Leuk. 2016;16(8):466-471.e1.

 8. Dasatinib (Sprycel) [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; June 2021.

 9. Cortes JE, Saglio G, Kantarjian HM, et al. Final 5-year study results of DASISION: The Dasatinib Versus Imatinib Study in Treatment-Naïve Chronic Myeloid Leukemia Patients Trial. J Clin Oncol. 2016;34(20):2333-2340.

10. Kantarjian H, Cortes J, Kim DW, et al. Phase 3 study of dasatinib 140 mg once daily versus 70 mg twice daily in patients with chronic myeloid leukemia in accelerated phase resistant or intolerant to imatinib: 15-month median follow-up. Blood. 2009;113(25):6322-6329.

11. Saglio G, Hochhaus A, Goh YT, et al. Dasatinib in imatinib-resistant or imatinib- intolerant chronic myeloid leukemia in blast phase after 2 years of follow-up in a phase 3 study: efficacy and tolerability of 140 milligrams once daily and 70 milligrams twice daily. Cancer. 2010;116(16):3852-3861.

12. Imatinib (Gleevec) [package insert]. East Hanover, NJ: Novartis Pharmaceuticals; August 2020.

13. Hochhaus A, Larson RA, Guilhot F, et al. Long-term outcomes of imatinib treatment for chronic myeloid leukemia. N Engl J Med. 2017;376(10):917-927.

14. Jabbour E, Kantarjian HM, Jones D, et al. Imatinib mesylate dose escalation is associated with durable responses in patients with chronic myeloid leukemia after cytogenetic failure on standard-dose imatinib therapy. Blood. 2009;113(10):2154-2160.

15. Talpaz M, Silver RT, Druker BJ, et al. Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: results of a phase 2 study. Blood. 2002;99(6):1928-1937.

16. Kantarjian HM, Cortes J, O’Brien S, et al. Imatinib mesylate (STI571) therapy for Philadelphia chromosome-positive chronic myelogenous leukemia in blast phase. Blood. 2002;99(10):3547-3553.

17. Nilotinib (Tasigna) [package insert]. East Hanover, NJ: Novartis; September 2021.

18. Hochhaus A, Saglio G, Hughes TP, et al. Long-term benefits and risks of frontline nilotinib vs imatinib for chronic myeloid leukemia in chronic phase: 5-year update of the randomized ENESTnd trial. Leukemia. 2016;30(5):1044-1054.

19. le Coutre PD, Giles FJ, Hochhaus A, et al. Nilotinib in patients with Ph+ chronic myeloid leukemia in accelerated phase following imatinib resistance or intolerance: 24-month follow-up results. Leukemia. 2012;26(6):1189-1194. doi:10.1038/leu.2011.323

20. Giles FJ, Kantarjian HM, le Coutre PD, et al. Nilotinib is effective in imatinib- resistant or -intolerant patients with chronic myeloid leukemia in blastic phase. Leukemia. 2012;26(5):959-962.

21. Yeung DT, Osborn MP, White DL, et al. TIDEL-II: first-line use of imatinib in CML with early switch to nilotinib for failure to achieve time-dependent molecular targets. Blood. 2015;125(6):915-923.

22. Asciminib (Scemblix) [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; October 2021.

23. Rea D, Mauro MJ, Boquimpani C, et al. A phase 3, open-label, randomized study of asciminib, a STAMP inhibitor, vs bosutinib in CML after 2 or more prior TKIs. Blood. 2021;138(21):2013-2041.

24. Hughes TP, Mauro MJ, Cortes JE, et al. Asciminib in chronic myeloidLleukemia after ABL kinase inhibitor failure. N Engl J Med. 2019;381(24):2315-2326.

25. Cortes JE, Hughes TP, Mauro MJ, et al. Asciminib, a first-in-class STAMP inhibitor, provides durable molecular response in patients with chronic myeloid leukemia harboring the T315I mutation: Primary efficacy and safety results from a phase 1 trial. Blood. 2020;136(Suppl 1):47-50.

26. Omacetaxine (Synribo) [package insert]. Parsippany, NJ: Teva Pharmaceuticals USA Inc; May 2021.

27. Cortes JE, Nicolini FE, Wetzler M, et al. Subcutaneous omacetaxine mepesuccinate in patients with chronic-phase chronic myeloid leukemia previously treated with 2 or more tyrosine kinase inhibitors including imatinib. Clin Lymphoma Myeloma Leuk. 2013;13(5):584-591.

28. Khoury HJ, Cortes J, Baccarani M, et al. Omacetaxine mepesuccinate in patients with advanced chronic myeloid leukemia with resistance or intolerance to tyrosine kinase inhibitors. Leuk Lymphoma. 2015;56(1):120-127.

29. Ponatinib (Iclusig) [package insert]. Lexington, MA: Takeda Pharmaceuticals America Inc; July 2021.

30. Cortes JE, Kim DW, Pinilla-Ibarz J, et al. A phase 2 trial of ponatinib in Philadelphia chromosome-positive leukemias. N Engl J Med. 2013;369(19):1783-1796.

31. Cortes JE, Kim DW, Pinilla-Ibarz J, et al. Ponatinib efficacy and safety in Philadelphia chromosome-positive leukemia: final 5-year results of the phase 2 PACE trial. Blood. 2018;132(4):393-404.

(Revised 2/2022; Chronic Myeloid Leukemia Guidelines v3.2022) © 2022 by Haymarket Media, Inc.

Topics:

Chronic Myeloid Leukemia Hematologic Cancers Treatment Regimens