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, Lydia; Guilhot, Joëlle; Krahnke, Tillmann; Guerci‐Bresler, Agnès; Druker, Brian J.; Larson, Richard A.; O’Brien, Stephen G.; So, Charlene; Massimini, Giorgio; Guilhot, François

doi:10.1182/blood-2006-02-001495

Cited by 204 publications

(141 citation statements)

References 25 publications

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“…The recent follow-up from the International Randomized Study of Interferon and ST1571 reported an estimated OS at 5 years of 89% for the imatinib cohort. 3 On the basis of these impressive results and those of others, 4,5 which further confirmed the superiority of imatinib to other therapies (for example, a-IFN, cytarabine), long-term tyrosine kinase inhibitor therapy has since become the gold standard for treatment of CML in first chronic phase (CP1).…”

Section: Introductionmentioning

confidence: 61%

Imatinib use either pre- or post-allogeneic hematopoietic cell transplantation (allo-HCT) does not increase cardiac toxicity in chronic myelogenous leukemia patients

Burke

Trotz

Luo

et al. 2009

Bone Marrow Transplant

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Since the introduction of imatinib mesylate, the role of allogeneic hematopoietic cell transplantation (allo-HCT) for CML has essentially been reserved for patients with advanced disease or imatinib resistance. In addition, there have been concerns regarding imatinib associated cardiac toxicity. We investigated the outcome of 61 patients with CML who received a myeloablative allo-HCT at the University of Minnesota between 1999 and 2006. The median age at HCT was 38.4 (range; 6.9-56.9) years. Thirty-seven patients were in first chronic phase and twenty-four patients in a second chronic or accelerated phase at the time of HCT. Twenty-six patients received imatinib therapy before or after HCT, and thirty-five patients either never received imatinib (n ¼ 32) or received it only at the time of relapse after HCT (n ¼ 3). OS and relapse-free survival (RFS) at 2 years was 69 and 55% for the imatinib group, and 57 and 49% for the non-imatinib group (P ¼ 0.57 and 0.95, respectively). There was no difference in the risk of relapse at 2 years between the groups. Symptomatic cardiac toxicity at 1 year was reported in three imatinib group (12%) and two nonimatinib group (6%) patients (P ¼ 0.44). Thus, patients treated with imatinib either before or after myeloablative allo-HCT had no increase in cardiac toxicity.

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Section: Introductionmentioning

confidence: 61%

Imatinib use either pre- or post-allogeneic hematopoietic cell transplantation (allo-HCT) does not increase cardiac toxicity in chronic myelogenous leukemia patients

Burke

Trotz

Luo

et al. 2009

Bone Marrow Transplant

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“…26,27 The survival benefits of imatinib could not be determined in the IRIS study because of the high rate of patient crossover, but they were confirmed by historic comparison studies. 28,29 A retrospective comparison of newly diagnosed patients with CML who received imatinib (n ¼ 279) or IFN (n ¼ 650) at The University of Texas M. D. Anderson Cancer Center (MDACC) demonstrated improved response and survival for imatinib-treated patients. 28 CCyR rates were 87% for imatinib-treated patients versus 28% for IFNtreated patients (P < .001).…”

Section: Imatinib Nilotinib Dasatinibmentioning

confidence: 99%

“…Another retrospective study that examined outcomes from the imatinib arm of the IRIS trial and the IFN/cytarabine arm of the CML91 trial was in complete concordance with the MDACC study. 29 The safety, response, and survival advantages of imatinib over IFN has led to broad acceptance of imatinib as the drug of choice for initial therapy of CML. [21][22][23] Assessing imatinib response and resistance…”

Section: Imatinib Nilotinib Dasatinibmentioning

confidence: 99%

Optimizing therapy for patients with chronic myelogenous leukemia in chronic phase

Kantarjian

Cortés

Rosée

et al. 2010

Cancer

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Identification of BCR‐ABL as the defining leukemogenic event in chronic myelogenous leukemia (CML) revolutionized the treatment of the disease. Imatinib, a potent BCR‐ABL inhibitor, is the standard of care for the first‐line treatment of patients with chronic‐phase CML because of its high long‐term response rates and favorable tolerability profile compared with previous standard therapies. However, resistance to imatinib develops in 2% to 4% of patients annually. For patients with acquired cytogenetic resistance to standard‐dose imatinib (400 mg daily), imatinib dose escalation (600‐800 mg daily) is an excellent first option for managing patients and achieving cytogenetic responses. However, for patients with primary resistance to imatinib, hematologic disease recurrence, or emergent BCR‐ABL kinase domain mutations, imatinib dose escalation may not be sufficient to control the disease. For these patients, the potent second‐generation tyrosine kinase inhibitors dasatinib and nilotinib are available. Both agents provide effective therapeutic options for patients with imatinib resistance or intolerance. For the current overview, the authors reviewed the data supporting the use of both dasatinib and nilotinib in imatinib‐resistant or imatinib‐intolerant patients, and they have highlighted the future of CML therapy. Overall, the article is intended to offer physicians a comprehensive review of the current literature and to provide data supporting various treatment options for patients with CML throughout the course of imatinib therapy and beyond. Cancer 2010. © 2010 American Cancer Society.

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“…Imatinib mesylate (Gleevec, Novartis Basel, Switzerland; STI571), a Kit, Abl and PDGFR inhibitor, induces apoptosis of the Ph 1 CML progenitors by suppressing the ability of BCR/ABL to phosphorylate substrates through competitive inhibition at the BCR/ABL ATP binding site (Druker et al, 1996). The development of the BCR/ABL tyrosine kinase inhibitor imatinib mesylate (Gleevec; formerly STI571) as the treatment of choice for chronic phase CML and its remarkable therapeutic effects suggest that blast crisis transition will be postponed for several years in the majority of CML patients (Deininger et al, 2005a;Roy et al, 2006). However, the persistence of BCR/ABL transcripts in a cohort of patients with complete cytogenetic response (Hughes et al, 2003) and the resistance of the primitive CML stem cell to imatinib treatment (Copland et al, 2006) raises the possibility that treatment with imatinib alone might delay but not prevent disease progression.…”

Section: CML Bcr/abl and Imatinibmentioning

confidence: 99%

ReSETting PP2A tumour suppressor activity in blast crisis and imatinib-resistant chronic myelogenous leukaemia

Perrotti

Neviani

2006

Br J Cancer

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The deregulated kinase activity of p210-BCR/ABL oncoproteins, hallmark of chronic myelogenous leukaemia (CML), induces and sustains the leukaemic phenotype, and contributes to disease progression. Imatinib mesylate, a BCR/ABL kinase inhibitor, is effective in most of chronic phase CML patients. However, a significant percentage of CML patients develop resistance to imatinib and/or still progresses to blast crisis, a disease stage that is often refractory to imatinib therapy. Furthermore, there is compelling evidence indicating that the CML leukaemia stem cell is also resistant to imatinib. Thus, there is still a need for new drugs that, if combined with imatinib, will decrease the rate of relapse, fully overcome imatinib resistance and prevent blastic transformation of CML. We recently reported that the activity of the tumour suppressor protein phosphatase 2A (PP2A) is markedly inhibited in blast crisis CML patient cells and that molecular or pharmacologic re-activation of PP2A phosphatase led to growth suppression, enhanced apoptosis, impaired clonogenic potential and decreased in vivo leukaemogenesis of imatinib-sensitive and -resistant (T315I included) CML-BC patient cells and/or BCR/ABL þ myeloid progenitor cell lines. Thus, the combination of PP2A phosphatase-activating and BCR/ABL kinase-inhibiting drugs may represent a powerful therapeutic strategy for blast crisis CML patients.

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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

Cited by 204 publications

References 25 publications

Imatinib use either pre- or post-allogeneic hematopoietic cell transplantation (allo-HCT) does not increase cardiac toxicity in chronic myelogenous leukemia patients

Imatinib use either pre- or post-allogeneic hematopoietic cell transplantation (allo-HCT) does not increase cardiac toxicity in chronic myelogenous leukemia patients

Optimizing therapy for patients with chronic myelogenous leukemia in chronic phase

ReSETting PP2A tumour suppressor activity in blast crisis and imatinib-resistant chronic myelogenous leukaemia

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