Low-Dose Dasatinib (50 mg Daily) Frontline Therapy in Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia: 5-Year Follow-Up Results

Gener-Ricos, Georgina; Haddad, Fady G.; Sasaki, Koji; Issa, Ghayas C.; Skinner, Jeffrey; Masárová, Lucia; Borthakur, Gautam; Alvarado, Yesid; Jabbour, Elias; Kantarjian, Hagop M.

doi:10.1016/j.clml.2023.05.009

Cited by 10 publications

(4 citation statements)

References 23 publications

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Section: Discussionmentioning

confidence: 98%

“…Previous studies showed the efficacy of lower dose (40 mg/day to 80 mg/day, mostly 50 mg/day) dasatinib therapy [2] , [3] , [4] , [5] , [6] , [7] , [8] , [9] ( Table 2 ). In addition, further lower doses (e.g., 20 mg/day or ≤20 mg/day) induced favorable outcomes [2] , [3] , [4] , [5] , [6] ( Table 2 ). Itamura et al reported that among 21 elderly patients with CML-CP, 91 % of patients administered the mean dasatinib dose of ≤50 mg/day achieved a molecular response of MR3 ( BCR-ABL1 IS < 0.1 %), MR4 ( BCR-ABL1 IS < 0.01 %), and MR4.5 ( BCR-ABL1 IS < 0.0032 %) in 96 %, 77 %, and 62 %, respectively, while 72 % of patients administered the mean dasatinib dose of ≤20 mg/day achieved a molecular response of MR3 and MR4 in 94 % and 74 %, respectively [2] .…”

Section: Discussionmentioning

confidence: 98%

“…Jabbour et al showed that the efficacy of 50 mg/day of dasatinib ( n = 83) was comparable to that of 100 mg/day of dasatinib ( n = 150), while the frequency of pleural effusion was lower in the 50 mg/day cohort than in the 100 mg/day cohort [4] . Gener-Ricos et al and Ahmed et al confirmed that the efficacy of 50 mg/day of dasatinib was feasible [ 5 , 6 ]. However, since even this dose sometimes caused grade 3 to 4 AEs, especially in elderly patients, they required more reduced doses of dasatinib.…”

Section: Discussionmentioning

confidence: 99%

“…We have experienced two cases who treated with intermittent low dose dasatinib therapy, achieving a favorable outcome for a long time. Here, we discuss the feasibility of intermittent low dose dasatinib therapy in elderly patients with CML-CP, comparing the efficacy and safety reported in the previous studies in which the outcome of lower dose TKI therapy are demonstrated [2] , [3] , [4] , [5] , [6] , [7] , [8] , [9] , [10] .…”

Section: Introductionmentioning

confidence: 98%

See 3 more Smart Citations

Long-term follow-up of efficacy and safety in elderly patients with chronic myeloid leukemia treated with intermittent low dose dasatinib therapy

Imamura,

Nakamura,

Hidaka

et al. 2024

Leukemia Research Reports

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

See 2 more Smart Citations

Long-term follow-up of efficacy and safety in elderly patients with chronic myeloid leukemia treated with intermittent low dose dasatinib therapy

Imamura,

Nakamura,

Hidaka

et al. 2024

Leukemia Research Reports

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Chronic myeloid leukemia: 2025 update on diagnosis, therapy, and monitoring

Jabbour,

Kantarjian

2024

American J Hematol

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Disease overviewChronic myeloid leukemia (CML) is a myeloproliferative neoplasm with an annual incidence of two cases/100 000. It accounts for approximately 15% of newly diagnosed cases of leukemia in adults.DiagnosisCML is characterized by a balanced genetic translocation, t(9;22) (q34;q11.2), involving a fusion of the Abelson murine leukemia (ABL1) gene from chromosome 9q34 with the breakpoint cluster region (BCR) gene on chromosome 22q11.2. This rearrangement is known as the Philadelphia chromosome. The molecular consequence of this translocation is the generation of a BCR::ABL1 fusion oncogene, which in turn translates into a BCR::ABL1 oncoprotein.Frontline therapyFour tyrosine kinase inhibitors (TKIs), imatinib, dasatinib, bosutinib, and nilotinib, are approved by the United States Food and Drug Administration (FDA) for first‐line treatment of newly diagnosed CML in the chronic phase (CML‐CP). Clinical trials with second and third‐generation TKIs in frontline CML‐CP therapy reported significantly deeper and faster responses but had no impact on survival prolongation, likely because of their potent efficacy and the availability of effective TKIs salvage therapies for patients who have a cytogenetic relapse with frontline TKI therapy. All four TKIs are equivalent if the aim of therapy is to improve survival. In younger patients with high‐risk disease and in whom the aim of therapy is to induce a treatment‐free remission status, second‐generation TKIs may be favored.Salvage therapyFor CML post‐failure on frontline therapy, second‐line options include second and third‐generation TKIs. Although potent and selective, these TKIs exhibit unique pharmacological profiles and response patterns relative to different patient and disease characteristics, such as patients' comorbidities and financial status, disease stage, and BCR::ABL1 mutational status. Patients who develop the T315I “gatekeeper” mutation display resistance to all currently available TKIs except ponatinib, asciminib, and olverembatinib. Allogeneic stem cell transplantation remains an important therapeutic option for patients with CML‐CP and failure (due to resistance) of at least two TKIs and for all patients in advanced‐phase disease. Older patients who have a cytogenetic relapse post‐failure on all TKIs can maintain long‐term survival if they continue a daily most effective/least toxic TKI, with or without the addition of non‐TKI anti‐CML agents (hydroxyurea, omacetaxine, azacitidine, decitabine, cytarabine, and others).

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Optimal frontline therapy of chronic myeloid leukemia today, and related musings

Kantarjian,

Begna,

Jabbour

et al. 2024

American J Hematol

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Low-Dose Dasatinib (50 mg Daily) Frontline Therapy in Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia: 5-Year Follow-Up Results

Cited by 10 publications

References 23 publications

Long-term follow-up of efficacy and safety in elderly patients with chronic myeloid leukemia treated with intermittent low dose dasatinib therapy

Long-term follow-up of efficacy and safety in elderly patients with chronic myeloid leukemia treated with intermittent low dose dasatinib therapy

Chronic myeloid leukemia: 2025 update on diagnosis, therapy, and monitoring

Optimal frontline therapy of chronic myeloid leukemia today, and related musings

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