Multicenter Independent Assessment of Outcomes in Chronic Myeloid Leukemia Patients Treated With Imatinib

Gambacorti‐Passerini, Carlo; Antolini, Laura; Mahon, F. X.; Guilhot, Joëlle; Deininger, Michael W.; Fava, Carmen; Nagler, Arnon; Casa, Chiara Maria Della; Morra, Enrica; Abruzzese, Elisabetta; D'Emilio, Anna; Stagno, Fabio; Coutre, Philipp le; Hurtado-Monroy, Rafael; Santini, Valeria; Martino, Bruno; Pane, Fabrizio; Piccin, Andrea; Giraldo, Pilar; Assouline, Sarit; Durosinmi, M. A.; Leeksma, O. C.; Pogliani, Enrico Maria; Puttini, Miriam; Jang, Eun Chul; Reiffers, J.; Valsecchi, Maria Grazia; Kim, Dong Wook

doi:10.1093/jnci/djr060

Cited by 376 publications

(258 citation statements)

References 21 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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“…Although the drug is the same and the clinical conditions too, failure to address an apparently trivial symptom can result, over time, in a lack of compliance, with serious consequences. Therefore attention to the organization of the CML clinic, the availability of a critical mass of patients and the realization that these aspects are at lease at important as the choice of TKI are of fundamental importance for an optimal clinical outcome [8,28].…”

Section: Logistics Of CML Treatmentmentioning

confidence: 99%

“…TKIassociated cutaneous reactions are typically self-limiting, and rashes may be managed with antihistamines or topical steroids, with oral steroids reserved for more severe cases [37]. Imatinib can also cause cutaneous edema, because of increased permeability of small vessels, due to its potent PDGFR inhibitory activity, and can result over extended periods of time in fragile skin [8].…”

Section: Th Anniversary Issuementioning

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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“…In fact, life expectancy of patients with CML-CP who have maintained a complete cytogenetic response on imatinib for 2 years is identical to that of an aged-matched control. 2 Unfortunately, recurrence of active leukemia is common if treatment is discontinued, even in patients whose disease has decreased to very low or undetectable levels as assessed by reverse transcription-PCR. This situation is commonly referred to as disease persistence and is different from resistance, which implies loss of response or the failure to attain a meaningful response in the first place.…”

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confidence: 99%

Stem cell persistence in chronic myeloid leukemia

Deininger

2012

Leukemia Suppl

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Tyrosine kinase inhibitors (TKIs) of BCR-ABL have turned chronic myeloid leukemia (CML) from a deadly disease into a chronic ailment. Unfortunately, evidence is accumulating that TKIs are not curative, since CML stem cells are not addicted to BCR-ABL, and persist despite TKI therapy. On closer view this is not surprising, as it reflects fundamental principles of CML pathogenesis. Strategies to eradicate CML stem cells will most likely be based on synthetic lethality though parallel inhibition of BCR-ABL and other critical pathways.

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Multicenter Independent Assessment of Outcomes in Chronic Myeloid Leukemia Patients Treated With Imatinib

Abstract: In this study, CML-related deaths were uncommon in CML patients who were in CCyR 2 years after starting imatinib, and survival was not statistically significantly different from that of the general population.

Cited by 376 publications

References 21 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

Stem cell persistence in chronic myeloid leukemia

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