Is it time to reconsider molecular response milestones in chronic myeloid leukemia?

Walia, Anushka; Prasad, Vinay

doi:10.1002/ajh.26867

Cited by 5 publications

(2 citation statements)

References 13 publications

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“…However, a lack of data shows that acting upon this outcome improves clinically relevant endpoints like OS. The current practice is switching CML patients to more expensive and toxic therapy when MMR milestones are unmet [26].…”

Section: Discussionmentioning

confidence: 99%

Real-world Imatinib Mesylate Treatment in Patients with Chronic Myeloid Leukemia: The Importance of Molecular Monitoring and the Early Molecular Response

et al. 2023

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Introduction Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder characterized by the Philadelphia (Ph) chromosome. After the introduction of imatinib mesylate (IM) in 2000, the natural history of the disease changed. Data on the treatment of CML with IM are from randomized clinical trials. Establishing whether these results can be reproduced or if caution is needed when extrapolating data to the general population with CML is essential. Objectives To evaluate the molecular response (MR) in patients with chronic-phase CML (CML-CP) not included in clinical studies and correlate them with the responses obtained in clinical trials. Methods Between January 2007 and January 2017, 227 patients newly diagnosed with CML-CP treated with IM as first-line treatment were included. This study is an observational, retrospective, and single-center study. Results At a median follow-up time of 7.3 years, 60.3% of the 227 patients who started IM were still on IM. Early molecular response (EMR) at 3 and 6 months was achieved by 74.2% and 65%, respectively. The median time to a MMR was nine months. The MR4.0 and MR4.5 were 67.2% and 51.1%, respectively. The overall survival (OS), progression-free survival (PFS), and event-free survival (EFS) of the patients who exclusively used IM were 91%, 91%, and 85.1%, respectively. Conclusion The results presented are similar to those described in prospective and randomized trials, demonstrating that the outcomes are reproducible in the real world. EMR at 3 and 6 months reflects better long-term responses, including higher rates of deeper molecular responses. Considering treatment costs, the absence of literature evidence of an impact on overall survival demonstrated by first-line second-generation tyrosine kinase inhibitors (TKIs), and the global OS of 85.8%, imatinib mesylate (IM) is still an excellent therapeutic option.

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Section: Discussionmentioning

confidence: 99%

Real-world Imatinib Mesylate Treatment in Patients with Chronic Myeloid Leukemia: The Importance of Molecular Monitoring and the Early Molecular Response

et al. 2023

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“…7 The latter observation is practically relevant considering the consensus rst-line drug of choice being imatinib, which might not necessarily be the most effective in rapidly inducing MMR/DMR, 8-10 and yet arguably the safest and least expensive, among the currently FDA-approved TKIs for CML, 11 the others being dasatinib, nilotinib, bosutinib, ponatinib, and asciminib. 9,[12][13][14][15][16][17][18][19][20][21] However, a substantial minority of patients with CML-CP are either intolerant or fail to achieve the desired response milestone with imatinib and, therefore, require treatment with an alternative TKI. 22 In this regard, our current preference as second-line drug of choice is dasatinib, based on its proven e cacy, even at a lower dose schedule, 23 and the nature of associated side effects seen with the other TKIs, especially in terms of nilotinib-associated vacular complications, including arterial occlusive events (AOEs).…”

Section: Introductionmentioning

confidence: 99%

Real-world experience with ponatinib therapy in chronic phase chronic myeloid leukemia: impact of depth of response on survival and prior exposure to nilotinib on arterial occlusive events

Al-Kali,

Litzow,

Begna

et al. 2023

Preprint

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We surveyed the performance of ponatinib, as salvage therapy, in a real-world setting of chronic phase chronic myeloid leukemia (CML-CP). Among 55 consecutive patients (median age 49 years) with relapsed/refractory CML-CP, 35 (64%) had failed ≥ 3 tyrosine kinase inhibitors (TKIs), 35 (64%) were pre-treated with nilotinib, and 14 (28%) harbored ABL1T315I. At start of ponatinib (median dose 30 mg/day), 40 patients were already in complete hematologic (CHR), 4 in complete cytogenetic (CCyR), 3 in major molecular (MMR) remission, while 8 had not achieved CHR (NR). Ponatinib improved the depth of response in 13 (33%), 3 (75%), 2 (66%), and 4 (50%) patients with CHR, CCyR, MMR, and NR, respectively (p = 0.02). At a median follow-up of 42 months, 13 (23%) deaths, 5 (9%) blast transformations, and 25 (45%) allogeneic transplants were recorded. Five/10-year post-ponatinib survival was 77%/58% with no significant difference when patients were stratified by allogeneic transplant (p = 0.94), ponatinib-induced deeper response (p = 0.28), or a post-ponatinib ≥ CCyR vs CHR remission state (p = 0.25). ABL1T315I was detrimental to survival (p = 0.04) but did not appear to affect response. Prior exposure to nilotinib was associated with higher risk of arterial occlusive events (AOEs; 11% vs 0%; age-adjusted p = 0.04). Ponatinib starting/maintenance dose (45 vs 15 mg/day) did not influence either treatment response or AOEs. Our observations support the use of a lower starting/maintenance dose for ponatinib in relapsed/refractory CML-CP but a survival advantage for deeper responses was not apparent and treatment might not overcome the detrimental impact of ABL1T315I on survival. The association between prior exposure to nilotinib and a higher risk of post-ponatinib AOEs requires further validation.

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Imatinib remains the best frontline therapy in patients with chronic myeloid leukemia: Critical analysis of the ASC4FIRST trial

Srinivasan,

Olivier,

Haslam

et al. 2024

American J Hematol

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Is it time to reconsider molecular response milestones in chronic myeloid leukemia?

Cited by 5 publications

References 13 publications

Real-world Imatinib Mesylate Treatment in Patients with Chronic Myeloid Leukemia: The Importance of Molecular Monitoring and the Early Molecular Response

Real-world Imatinib Mesylate Treatment in Patients with Chronic Myeloid Leukemia: The Importance of Molecular Monitoring and the Early Molecular Response

Real-world experience with ponatinib therapy in chronic phase chronic myeloid leukemia: impact of depth of response on survival and prior exposure to nilotinib on arterial occlusive events

Imatinib remains the best frontline therapy in patients with chronic myeloid leukemia: Critical analysis of the ASC4FIRST trial

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