How <scp>I</scp> treat newly diagnosed chronic myeloid leukemia in 2015

Gambacorti‐Passerini, Carlo; Piazza, Rocco

doi:10.1002/ajh.23887

Cited by 19 publications

(15 citation statements)

References 62 publications

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“…Imatinib is recognized as one of the best and safest first line treatments for chronic phase CML [5][6][7] and is associated with a normal or near-normal life expectancy among treated patients [8,9], even at diagnosis [10]. Imatinib induces complete cytogenetic response (CCyR) in up to 86% of CML patients, while major molecular responses (MMR) develop in 33-90% of the patients according to treatment duration [10,11].…”

Section: Introductionmentioning

confidence: 99%

Age and dPCR can predict relapse in CML patients who discontinued imatinib: The ISAV study

et al. 2015

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Imatinib is effective for the treatment of chronic myeloid leukemia (CML). However even undetectable BCR-ABL1 by Q-RT-PCR does not equate to eradication of the disease. Digital-PCR (dPCR), able to detect 1 BCR-ABL1 positive cell out of 10 7 , has been recently developed. The ISAV study is a multicentre trial aimed at validating dPCR to predict relapses after imatinib discontinuation in CML patients with undetectable Q-RT-PCR. CML patients under imatinib therapy since more than 2 years and with undetectable PCR for at least 18 months were eligible. Patients were monitored by standard Q-RT-PCR for 36 months. Patients losing molecular remission (two consecutive positive Q-RT-PCR with at least 1 BCR-ABL1/ABL1 value above 0.1%) resumed imatinib. The study enrolled 112 patients, with a median follow-up of 21.6 months. Fifty-two of the 108 evaluable patients (48.1%), relapsed; 73.1% relapsed in the first 9 months but 14 late relapses were observed between 10 and 22 months. Among the 56 not-relapsed patients, 40 (37.0% of total) regained Q-RT-PCR positivity but never lost MMR. dPCR results showed a significant negative predictive value ratio of 1.115 [95% CI: 1.013-1.227]. An inverse relationship between patients age and risk of relapse was evident: 95% of patients <45 years relapsed versus 42% in the class 45 to <65 years and 33% of patients 65 years [P(v 2 ) < 0.0001]. Relapse rates ranged between 100% (<45 years, dPCR1) and 36% (>45 years, dPCR-). Imatinib can be safely discontinued in the setting of continued PCR negativity; age and dPCR results can predict relapse.

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Section: Introductionmentioning

confidence: 99%

Age and dPCR can predict relapse in CML patients who discontinued imatinib: The ISAV study

et al. 2015

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“…These in vitro results have been validated in several clinical studies [12,27] and thus provide a valuable tool for physicians treating CML patients. The different TKIs present non overlapping spectrum of activity: ponatinib is the TKI with the largest coverage and the only one active against the T315I mutation; dasatinib and bosutinib cover well mutations affecting the "p loop" of Abl kinase domain (residues 250-255), at difference from nilotinib, which is also inactive against the F359I/V mutants.…”

Section: Treatment Optionsmentioning

confidence: 76%

“…A number of studies [12,28] show that the impact of TKI therapy (mostly imatinib) on CML control can vary by a factor of >4 depending on the local logistic conditions: organization of care, spaces available, availability of side support personnel (nurses, patient associations. .…”

Section: Logistics Of CML Treatmentmentioning

confidence: 99%

Chronic myeloid leukemia: Second‐line drugs of choice

Gambacorti‐Passerini

Cordani

2015

American J Hematol

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The efficacy of second-line treatment for chronic myeloid leukemia (CML) plays an important role in allowing CML patients to enjoy a normal life expectancy. Four tyrosine kinase inhibitors (TKIs) are presently available: bosutinib, dasatinib, nilotinib, ponatinib. Each one has different safety and activity profiles, which are reviewed here. No controlled studies are available to guide treatment decision, which must be based on the characterization of leukemic cells, especially in cases of resistance to TKI, coupled with the safety profile of each TKI. Patient comorbidities also play an important role in the treatment decision, which can achieve a new durable response in over 50% of treated patients.

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“…The data have been analyzed in multiple comprehensive reviews and incorporated into widely-practiced guidelines. [1][2][3][4][5] Many of these trials have been conducted by pharmaceutical company sponsors, leading to registration by health authorities; others have been designed and conducted by publically funded cooperative clinical trials groups. After imatinib was shown to be more effective and better tolerated than the previous standard therapy of rIFN␣ and low-dose cytarabine in the IRIS trial, imatinib has generally been the standard comparator at the initial dose of 400 mg daily for all of these trials.…”

Section: Randomized Clinical Trialsmentioning

confidence: 99%

Is there a best TKI for chronic phase CML?

Larson

2015

Hematology

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The development of BCR/ABL1 tyrosine kinase inhibitors (TKIs) over the past 20 years has dramatically improved the outcomes for patients with every stage of Philadelphia chromosome-positive (Phϩ) chronic myeloid leukemia (CML). Clinicians now have access to 5 oral, generally well-tolerated, and highly effective TKIs. How should these agents be used for an individual patient to ensure the best possible duration and quality-of-life, to avoid treatment-related complications, and potentially to achieve a cure at an affordable cost? Because CML patients may need to continue TKI therapy indefinitely, the long-term safety of each treatment option must be considered. Evidence-based care requires an understanding of the optimal use of these drugs, their specific early and late toxicities, the prognostic significance of achieving treatment milestones, and the critical importance of molecular monitoring. Efficacy is important, but treatment choice does not depend only on efficacy. Choosing among various treatment options is informed by understanding the distinct benefits and risks of each agent, along with careful consideration of patient-specific factors, such as risk status, age, and comorbidities. Learning Objectives• To compare the efficacy and safety of frontline BCR/ABL1 tyrosine kinase inhibitors in newly diagnosed chronic phase CML • To recognize the utility of risk assessment and molecular monitoring to individualize treatment • To understand the importance of early molecular response assessment with respect to long-term outcomesA 58-year-old man presented with asymptomatic leukocytosis. His past medical history included hypertension, adequately controlled with metoprolol, and diabetes for which he took metformin. His physical exam was notable only for an enlarged spleen palpable 5 cm below the left costal margin. His white blood cell count was 128 000/L with a predominance of neutrophilic cells, 2% blasts, 3% eosinophils, and 2% basophils. His hemoglobin was 13 g/dL and platelet count 640 000/L. Qualitative RT-PCR for BCR/ABL1 on blood was positive for the p210 transcript. Is there a best TKI for this patient with newly diagnosed chronic myeloid leukemia (CML) in chronic phase? The development of tyrosine kinase inhibitors (TKIs) over the past 20 years has dramatically altered the management as well as the outcomes for patients with every stage of Philadelphia chromosome-positive (Phϩ), BCR-ABL1ϩ, CML. Over a relatively short period of time, treatment recommendations have evolved from allogeneic hematopoietic cell transplantation (alloHCT) early in the disease course or recombinant interferon-alfa (rIFN␣), to the availability of 5 oral, generally well-tolerated and highly effective TKIs. Three (imatinib, dasatinib, and nilotinib) are approved for front-line use. Two others (bosutinib and ponatinib) are approved for intolerance or failure of prior TKI therapy. How should these agents be used for an individual patient to ensure the best possible duration and quality-oflife, to avoid treatment-related complications,...

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How I treat newly diagnosed chronic myeloid leukemia in 2015

Cited by 19 publications

References 62 publications

Age and dPCR can predict relapse in CML patients who discontinued imatinib: The ISAV study

Age and dPCR can predict relapse in CML patients who discontinued imatinib: The ISAV study

Chronic myeloid leukemia: Second‐line drugs of choice

Is there a best TKI for chronic phase CML?

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