my personal edition > chronic myeloid leukemia (cml) > news


  E-Mail this DGDispatch to a colleague

DGDispatch

Suboptimal Response of Imatinib 400 mg in Chronic Myeloid Leukaemia Indicates Need for Early Intervention: Presented at EHA

By Chris Berrie

BERLIN -- June 9, 2009 -- In agreement with the European LeukaemiaNet (ELN) recommendations, suboptimal response with imatinib 400 mg treatment within 12 months for patients with early chronic-phase (ECP) chronic myeloid leukaemia (CML) indicates the need for early intervention to reduce higher rates of negative events that can occur beyond 12 months of treatment, according to researchers at the 14th Congress of the European Hematology Association (EHA).

This combined analysis of 2 trials of the Italian Group for Adult Haematologic Diseases (GIMEMA) CML Working Party was presented by Fausto Castagnetti, MD, Department of Haematology and Oncological Sciences, L. and A. Serągnoli S. Orsola Malpighi Hospital, University of Bologna, Bologna, Italy, here on June 6.

The recently defined ELN recommendations are designed to aid identification of patients with CML who are responding poorly to imatinib 400 mg. Indeed, as Dr. Castagnetti said, "We know that imatinib obtains around 70% of complete cytogenetic response, but we also know that some patients do not achieve this."

With recent evidence of significantly poorer progression-free survival (PFS) and lower probability of complete cytogenetic response (CCgR) in these patients, the analysis was designed to determine the outcome of suboptimal responders in a nationwide multicentre setting.

The first trial analysed was a phase 3 study of imatinib 400 mg versus 800 mg in high-Sokal-risk ECP CML (CML/022) and the second was an observational trial of imatinib 400 mg in ECP CML (CML/023). The trials included 423 patients.

Response monitoring was based on conventional cytogenetic examination every 6 months, with quantitative molecular evaluations after 3, 6, and 12 months and every 6 months thereafter.

Major molecular response (MMR) was classified as a BCR-ABL/ABL ratio <0.1%, with suboptimal response and failure classified according to ELN recommendations. Death was included as failure, and optimal response was classified as nonsuboptimal and nonfailure.

Although optimal responses at 3, 6, 12, and 18 months were high at 96.5%, 81.1%, 79.4%, and 61.7%, suboptimal responses according to ELN criteria were 1.7%, 4.7%, 7.6%, and 10.2%.

At 3 months, although suboptimal responders had a slightly but significantly lower probability of subsequent CCgR than optimal responders (71% vs 93%, respectively; P = .04), no significant differences were seen for event-free survival (EFS), failure-free survival (FFS), PFS, or overall survival (OS).

Suboptimal responders were well discriminated from optimal responders, with significantly lower probability of CCgR by 6 and 12 months (55% vs 98% and 85% vs 98%, respectively; P < .0001), MMR (63% vs 98% and 81% vs 96%; P < .0001), EFS (33% vs 79% and 42% vs 85%; P < .0001), and FFS (51% vs 85% and 49% vs 92%; P < .0001), with no significant differences for PFS and OS.

At 18 months, the lower probability of subsequent MMR remained, although EFS, FFS, PFS, and OS were comparable with those of the optimal responders.

Noting that further studies are needed to confirm the data, Dr. Castagnetti said, "At 6 and 12 months, suboptimal responders have poorer outcome than optimal responders in terms of complete cytogenetic and major molecular response and have a higher probability to have an event and to fail treatment."

"In our opinion, it is important to understand, during the first year of treatment, if a patient has optimal response," he concluded.

[Presentation title: Suboptimal Response to Imatinib 400 mg Daily in Chronic Myeloid Leukemia in Early Chronic Phase: A GIMEMA CML WP Analysis of 423 Consecutive Patients. Abstract 0628]

E-Mail this DGDispatch to a colleague

To print, use this version