Imatinib and pegylated human recombinant interferon-α2b in early chronic-phase chronic myeloid leukemia

Baccarani, Michele; Martinelli, Giovanni; Rosti, Gianantonio; Trabacchi, Elena; Testoni, Nicoletta; Bassi, Simona; Amabile, Marilina; Soverini, Simona; Castagnetti, Fausto; Cilloni, Daniela; Izzo, Barbara; Vivo, Antonio De; Messa, Emanuela; Bonifazi, Francesca; Poerio, Angela; Luatti, Simona; Gatto, Emilia; Alberti, Daniele; Fincato, G.; Russo, Domenico; Pane, Fabrizio; Saglio, Giuseppe

doi:10.1182/blood-2004-03-0826

Cited by 90 publications

(47 citation statements)

References 51 publications

(46 reference statements)

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“…Phase 2 studies have been recently conducted with preliminary interesting results. 26,27 Improvement of tolerance and efficacy with pegylated formulation of IFN-␣ is another promising approach. 27 The potential beneficial effect of IFN-␣ or Ara-C combined with imatinib is being evaluated in large phase 3 trials.…”

Section: Discussionmentioning

confidence: 99%

Survival advantage from imatinib compared with the combination interferon-α plus cytarabine in chronic-phase chronic myelogenous leukemia: historical comparison between two phase 3 trials

Roy

Guilhot

Krahnke

et al. 2006

Blood

204

129

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In the multinational IRIS study comparing imatinib with interferon plus cytarabine (IFN/Ara-C) in patients with newly diagnosed chronic-phase chronic myelogenous leukemia (CP CML), imatinib demonstrated significantly higher rates of complete cytogenetic responses (CCyRs) and improved progression-free survival (PFS). However, because of a high early crossover rate to imatinib, survival benefit was not assessable. Here, we report the result of a study comparing long-term outcome of patients included in 2 prospective randomized trials: 551 patients assigned to imatinib in the IRIS trial from 2000 to 2001 and 325 patients who received the combination IFN/Ara-C in the CML91 trial between 1991 and 1996 before imatinib was available. With a follow-up of 42 months for both groups of patients, estimated CCyR, survival free of transformation, and overall survival were significantly higher with imatinib compared with IFN/Ara-C (P < .001, P ‫؍‬ .004, and P < .001, respectively). Improved overall survival was also confirmed within different Sokal prognostic risk groups. Of interest, among all patients who achieved major cytogenetic response or CCyR at 12 months, the survival rate was similar irrespective of their treatment. In con

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Section: Discussionmentioning

confidence: 99%

Survival advantage from imatinib compared with the combination interferon-α plus cytarabine in chronic-phase chronic myelogenous leukemia: historical comparison between two phase 3 trials

Roy

Guilhot

Krahnke

et al. 2006

Blood

204

129

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“…An overview of the included articles is given in Online Supplementary Table S3. 14,15, Only 19 peer review articles were analyzed and reported in the Results section.Eight publications came from Europe, 14,15,18,19,21,24,25,30 5 from the US, 20,23,[31][32][33] 5 from Asia 22,26,28,29,35 and one from Australia.27 Almost half of the included studies were retrospective (9 of 19) and mainly conducted in the US and Asia 38,41,42,45,49,52,53 while half of the European studies were prospective (4 of 8). 14,15,18,24 …”

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confidence: 99%

Measurement of adherence to BCR-ABL inhibitor therapy in chronic myeloid leukemia: current situation and future challenges

et al. 2014

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Correspondence: Lucien.Noens@uzgent.be BCR-ABL inhibitors for treating chronic myeloid leukemia in chronic phase have transformed a previously incurable malignancy into a manageable condition. However, suboptimal medication adherence has been observed with these agents affecting clinical outcomes and healthcare costs. In order to raise awareness of the problem of adherence, and before developing pragmatic strategies to enhance medication adherence, a deep understanding of the best approaches for measuring adherence in chronic myeloid leukemia patients and identifying non-adherence is required. A systematic literature review on the prevalence, measurement methods, consequences and risk factors for non-adherence to BCR-ABL inhibitors and adherence-enhancing interventions was performed and critically appraised. Of the 19 included articles, 9 were retrospective. Average adherence varied from 19% to almost 100% of the proportion of prescribed drug taken, but it was measured through various different methods and within different study groups. Suboptimal adherence was associated with a negative impact on both clinical and economic outcomes. There is a lack of supportive evidence demonstrating a difference in adherence across BCR-ABL inhibitors and even contradictory results between the 2 nd generation inhibitors. Drug-related adverse events and forgetfulness were common reasons for intentional and unintentional non-adherence, respectively, but further research is required to identify additional reasons behind non-adherence or patients at risk of non-adherence. Non-adherence in chronic myeloid leukemia patients treated with BCR-ABL inhibitors is common and associated with critical outcomes. However, this review highlights important existing gaps, reveals inconsistent definitions, and a lack of standardized methods for measuring adherence in chronic myeloid leukemia. All require further investigation. ABSTRACT © F e r r a t a S t o r t i F o u n d a t i o nAnalyses statement for systematic reviews. 16 Publication database (EMBASE, PubMed, and Cochrane Library) specific search terms consisted of both single and MeSH terms for the disease, adherence and BCR-ABL inhibitor therapy (Online Supplementary Table S1). The last search was conducted on December 20 th , 2011. Full-text references were provided for the eligible abstracts that were published after completion of the search process and the analyses. In addition, and due to the lack of existing evidence of adherence in CML, clinical and economic conference proceedings were also searched with a time limit of three years. Preliminary inclusion (or exclusion) of a specific study or conference abstract was based on review of the title and abstract by 2 independent reviewers against pre-specified criteria (Table 1). Final inclusion of the study was based on an in-depth review of the full manuscript. Multiple variables were extracted from the articles to answer study objectives (Online Supplementary Table S2). The analysis was descriptive only. Since abstracts in conference pr...

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“…Seventy-six patients were treated with the combination of imatinib 400 mg/daily and PegIFNα, at doses ranging from 50μg to 150 μg weekly, 16 while 419 patients were treated with imatinib 400 mg/daily alone. Patients' characteristics are detailed in Table 1.…”

Section: Resultsmentioning

confidence: 99%

“…[16][17][18][19] All patients gave written informed consent to the studies which were approved by the Ethics Committee of each participating institution and conducted according to the principles of the Helsinki declaration. Briefly, cytogenetic analysis was performed by standard chromosome banding analysis of marrow metaphases and cytogenetic response was rated according to the European LeukemiaNet guidelines.…”

Section: Design and Methodsmentioning

confidence: 99%

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The response to imatinib and interferon- is more rapid than the response to imatinib alone: a retrospective analysis of 495 Philadelphia-positive chronic myeloid leukemia patients in early chronic phase

Palandri¹,

Castagnetti²,

Iacobucci³

et al. 2010

Haematologica

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Before the introduction of imatinib, interferon α-based regimens were the gold standard for treatment of early chronic phase chronic myeloid leukemia patients. The combination of IFN-α with imatinib is currently being investigated in at least two large clinical trials, the German CML Study IV and the French SPIRIT trial. We reviewed the cytogenetic and molecular responses of 76 early chronic phase chronic myeloid leukemia patients who were treated with imatinib and interferon-α and of 419 early chronic phase chronic myeloid leukemia patients treated with imatinib alone front-line. The complete cytogenetic response rate was higher in the IM+IFN-α group than in the imatinib group at six months (60% vs. 42%; P=0.003), but not at 48 months (88% vs. 88%). The durability of the complete cytogenetic response was similar in the two groups with 94% and 91% of complete cytogenetic responders in continuous complete cytogenetic response at 48 months (P=0.56). The major molecular response rate was higher in the IM+IFN-α group at six months (58% vs. 34%; P=0.0001) and 12 months (67% vs. 47%; P=0.001) but not later on (65% vs. 57% at 48 months; P=0.25). Overall and progression free survival were comparable in the two groups; a significant trend to a better event free survival was observed in patients treated with PegIFNα (91% vs. 78%; P=0.02). These data suggest that the response to the combination treatment is more rapid. It is not yet known how much a rapid reduction will influence the longer-term overall and progression free survival, and the cure rate.Key words: imatinib, interferon α, molecular response, chronic myeloid leukemia. IntroductionBefore 2000, interferon α (IFN-α) based regimens were the gold standard for treatment of early chronic phase chronic myeloid leukemia (ECP-CML) patients. The complete cytogenetic response (CCgR) ranged between 10% and 30%, and complete responders survived longer than ten years.1 After the introduction of the BCR-ABL tyrosine kinase inhibitor imatinib mesylate (IM; Glivec; Gleevec, Novartis Pharma, NJ, USA), 2 imatinib became the established first-line treatment of CML where it achieved a complete cytogenetic response in about 80% of the patients. 3,4 Despite many studies, the mechanism of action of IFN-α in CML is still poorly understood, 5-13 but it is believed that IFN-α enhances the antileukemic immune response and may target Philadelphia-positive stem cells. Currently, the role of IFN-α in combination with imatinib is being investigated in large clinical trials, like the German CML Study IV 14 and the French SPIRIT trial. 15 In an interim analysis of the French study, it has been reported that patients treated with imatinib and IFN-α had better cytogenetic responses at six months and better molecular responses at 18 months than those patients treated front-line with imatinib 400 mg alone.Years ago, the GIMEMA CML Working Party performed an exploratory study of a combination of imatinib and IFN-α front-line and reported that the compliance to the combination was poor. 16,17 The re...

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Imatinib and pegylated human recombinant interferon-α2b in early chronic-phase chronic myeloid leukemia

Cited by 90 publications

References 51 publications

Survival advantage from imatinib compared with the combination interferon-α plus cytarabine in chronic-phase chronic myelogenous leukemia: historical comparison between two phase 3 trials

Survival advantage from imatinib compared with the combination interferon-α plus cytarabine in chronic-phase chronic myelogenous leukemia: historical comparison between two phase 3 trials

Measurement of adherence to BCR-ABL inhibitor therapy in chronic myeloid leukemia: current situation and future challenges

The response to imatinib and interferon- is more rapid than the response to imatinib alone: a retrospective analysis of 495 Philadelphia-positive chronic myeloid leukemia patients in early chronic phase

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