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

Abstract

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.

Optimizing therapy for patients with chronic myelogenous leukemia in chronic phase

“…From Year 1 to Year 6, the annual event rate (loss of CHR, loss of MCyR, progression to accelerated phase/blast crisis [AP/BC], or death) on imatinib decreased over time (3.3%, 7.5%, 4.8%, 1.7%, 0.8%, and 0.4% for Years 1-6, respectively). 23 There was a downward trend in the risk of disease progression on imatinib, with a 0.4% event rate (including loss of response) and a 0% rate of transformation to AP/BC between Years 5 and 6. Approximately 83% of patients were event-free, and 93% were free of progression to AP or BC at 6 years on imatinib treatment.…”

“…23 No new serious AEs were identified between Years 5 and Year 6. Furthermore, first-line treatment with imatinib did not affect later Figure 3.…”

“…After 6 years of imatinib therapy, long-term response rates remained high. 23,24 Of the 456 patients who achieved a CCyR on imatinib therapy, 325 patients (71%) were still on study treatment and maintained a CCyR at 6 years. From Year 1 to Year 6, the annual event rate (loss of CHR, loss of MCyR, progression to accelerated phase/blast crisis [AP/BC], or death) on imatinib decreased over time (3.3%, 7.5%, 4.8%, 1.7%, 0.8%, and 0.4% for Years 1-6, respectively).…”

Antibody-based detection of protein phosphorylation status to track the efficacy of novel therapies using nanogram protein quantities from stem cells and cell lines

“…Tyrosine kinase inhibitor (TKI) therapy using imatinib mesylate (IM) has been shown to inhibit PTK activity in CML [15][16][17][18] . The use of TKIs has improved clinical outcomes markedly for the majority of patients with chronic phase (CP) CML who achieve sustained cytogenetic and molecular response 19,20 . Nonetheless second and third generation TKIs have been developed in response to BCR-ABL mutations inferring resistance to treatment (for review see O'Hare 21 ).…”

Towards novel paradigms for cancer therapy

“…BCR-ABL displays constitutive kinase activity, which results in the deregulated activation of signaling cascades that promote cell proliferation and survival (Shtivelman et al, 1985;. The first compound that successfully inhibited the aberrant BCR-ABL kinase activity and displayed clinical efficacy was imatinib mesylate (Druker, 2001), which has considerably increased the survival rate of CML patients (88% for 6 years) and decreased the need of hematopoietic stem cell transplantation (Hochhaus et al, 2009). At present, two other inhibitors have been approved and can be used to treat patients refractory to imatinib Cortes et al, 2007;le Coutre et al, 2008).…”