In reply to 'Cardiotoxicity of the cancer therapeutic agent imatinib mesylate'

Hatfield, Alan K.; Owen, Samantha; Pilot, Paul Richard

doi:10.1038/nm0107-13a

Cited by 88 publications

(32 citation statements)

References 3 publications

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“…The Novartis clinical database of registration trials consisting of 2327 patients has been examined for cardiac AEs. 25 Only 12 cases (0.5%) of CHF were identified. When related to imatinib exposure over the time period (5595 patient years), the incidence of CHF was 0.2%, consistent with the findings in other large series.…”

Section: Iris 6-year Follow-upmentioning

confidence: 99%

Six-year follow-up of patients receiving imatinib for the first-line treatment of chronic myeloid leukemia

et al. 2009

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Imatinib mesylate is considered standard of care for firstline treatment of chronic phase chronic myeloid leukemia (CML-CP). In the phase III, randomized, open-label International Randomized Study of Interferon vs STI571 (IRIS) trial, previously untreated CML-CP patients were randomized to imatinib (n ¼ 553) or interferon-a (IFN) plus cytarabine (n ¼ 553). This 6-year update focuses on patients randomized to receive imatinib as first-line therapy for newly diagnosed CML-CP. During the sixth year of study treatment, there were no reports of disease progression to accelerated phase (AP) or blast crisis (BC). The toxicity profile was unchanged. The cumulative best complete cytogenetic response (CCyR) rate was 82%; 63% of all patients randomized to receive imatinib and still on study treatment showed CCyR at last assessment. The estimated event-free survival at 6 years was 83%, and the estimated rate of freedom from progression to AP and BC was 93%. The estimated overall survival was 88%--or 95% when only CMLrelated deaths were considered. This 6-year update of IRIS underscores the efficacy and safety of imatinib as first-line therapy for patients with CML.

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Section: Iris 6-year Follow-upmentioning

confidence: 99%

Six-year follow-up of patients receiving imatinib for the first-line treatment of chronic myeloid leukemia

et al. 2009

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“…[11][12][13] In each of these reports, cardiac failure and left ventricular dysfunction, which was possibly or probably related to imatinib therapy, were either not identified 11 or were found to occur rarely (0.04%/year) as in the International Randomized Study of Interferon and ST1571 trial. 12 Atallah et al 13 recently reviewed over 1200 CML patients treated with imatinib and reported the presence of CHF in 22 of the 1276 (1.7%) patients. These 22 patients had a median age of 68 (range; 50-83) years with eighteen (82%) having an earlier diagnosed cardiovascular illness leaving the authors to conclude that although the potential of cardiac related toxicity does exist while on imatinib, it is a rare event mainly seen in elderly patients with a pre-existing cardiac condition.…”

Section: Discussionmentioning

confidence: 99%

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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“…In fact, a retrospective analysis of six imatinib monotherapy trials, comprising 2327 patients with 5595 years of patient exposure (median exposure duration, 2.4 years), revealed a congestive heart failure incidence of 0.2%. 30 Furthermore, retrospective analysis of the International Randomized Study of Interferon and STI571 (IRIS) in Chronic Myeloid Leukemia trial, which compared IFN þ cytarabine (Ara-C) with imatinib in 1106 newly diagnosed patients with CML in chronic phase (CP), found that the incident cases of cardiac failure and left ventricular dysfunction possibly or probably related to study medication exposure was 0.04% per year (1 case in 2309 years of patient exposure) for patients receiving imatinib vs 0.75% per year (4 cases in 536 years of patient exposure) in patients receiving IFN þ Ara-C. 30 More recently, a retrospective analysis of 219 patients with gastrointestinal stromal tumors or other sarcomas receiving imatinib therapy showed rare occurrence of congestive heart failure, observed in only one elderly patient with known prior cardiac disease. 31 Taken together, it appears that imatinib has little clinical impact on cardiac function.…”

Section: Tablementioning

confidence: 99%

Class effects of tyrosine kinase inhibitors in the treatment of chronic myeloid leukemia

2009

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Tyrosine kinase inhibitors have revolutionized the treatment of chronic myeloid leukemia (CML), offering patients several targeted therapeutic options that provide the possibility of sustained remissions and prolonged survival. With the availability of imatinib, nilotinib and dasatinib, physicians must weigh the efficacy and safety profile of each agent when choosing the best therapeutic option for individual patients. Each agent targets tyrosine kinases within the cell uniquely to cause the desired antiproliferative effect. In addition to inhibiting the BCR-ABL kinase, imatinib and nilotinib target the same array of other tyrosine kinases, including c-KIT and plateletderived growth factor receptor (PDGFR), albeit with differing potencies. While targeting BCR-ABL with the highest potency among approved agents in CML, dasatinib also targets a broad array of off-target kinases, including SRC family members, PDGFR and EPHB4. The differences in kinase inhibition profiles among these agents in vitro probably account for the differing clinical safety profiles of these agents. This paper reviews the various kinases inhibited by imatinib, nilotinib and dasatinib, and describes the potential impact of kinase inhibition on the efficacy and safety of each agent.

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In reply to 'Cardiotoxicity of the cancer therapeutic agent imatinib mesylate'

Cited by 88 publications

References 3 publications

Six-year follow-up of patients receiving imatinib for the first-line treatment of chronic myeloid leukemia

Six-year follow-up of patients receiving imatinib for the first-line treatment of chronic myeloid leukemia

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

Class effects of tyrosine kinase inhibitors in the treatment of chronic myeloid leukemia

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