Five Year Follow-Up Results of a Phase II Trial in Patients with Late Chronic Phase (L-CP) Chronic Myeloid Leukemia (CML) Treated with Imatinib Who Are Refractory/Intolerant of Interferon-α.

Abstract

Abstract Background Imatinib is effective in L-CP CML patients (Pts), but response duration is unknown. From 12/1999 to 05/2000, the Novartis study STI571A110 recruited 454 Pts with confirmed diagnosis of CP CML. Pts were hematologically (n=133) or cytogenetically resistant/refractory (n=160) or intolerant (n=161) to IFN. Median time since diagnosis was 34 months (m). Pts were evaluated for best major and complete cytogenetic response (MCyR and CCyR), time to progression to accelerated phase (AP) or blast crisis (BC), and overall survival (OS). This abstract includes data up to 56 m after the first patient and more than 48 m after last patient started treatment. Results: Median drug exposure as of 31-Jul-04 was 50 m. The initial daily dose was 400 mg. Dose increases after a median of 14 m were reported in 227 (50%) Pts. The table below summarizes discontinuation reasons, best responses observed and the estimated long-term outcomes at 48 m. n=454 (%) [95% Conf intervals] Still on Treatment 269 (59.3) Discontinued 185 (40.7) Progression/deaths from any cause 105 (23.1) AEs/toxicities 32 (7.0) BMT 5 (1.1) Withdrew consent/Lost/Admin. problems 43 (9.5) Pts achieving MCyR (includes CCyR) 301 (66.3) Pts achieving CCyR 248 (54.6) % Pts free of progression to AP/BC at 48 m (74.6) [70.4–78.9] OS at 48 m (82.4) [78.9–86.0] Median time to CCyR was 8.3 m [8.3–8.6 m]; 45 of the 248 Pts achieved CCyR after dose increase. The yearly risk of progression to AP/BC did not increase when considering all patients (7.8%, 6.0%, 7.2% and 7.1% within year 1,2,3,4 respectively). The corresponding risk rates for patients in MCyR at 3 m were 2.7%, 0.7%, 2.2%, 2.4%. Using the 3-m (and 12 m) landmark (n=446 or 421), Pts with CCyR, PCyR and minor CyR had an estimated OS at 48 m of 94(94)%, 93(94) %, 86(92) %, whereas Pts with only minimal CyR or no CyR had estimated 4-year OS of 85(78) % and 77(71) %, respectively. Among Pts who achieved MCyR and arrived to 48m of follow-up, 79% [74–84] maintain it; this value compares with 86% [80–92] for Pts with MCyR within 3 m. The following figure shows the duration of MCyR according to the time when MCyR was reached. Pts who had MCyR by the 3rd m did significantly better than the other groups (p= 0.02). However a MCyR obtained at a late time point (>12 m) has a duration similar to the entire cohort. Half of the Pts who lost MCyR did not progress to AP while on study. Conclusion: Imatinib treatment for L-CP CML Pts failing IFN therapy is effective and produces durable cytogenetic responses and survival, with more than 80% Pts alive at 48 m and no evident increase in progression rate over time. Even Pts who failed to achieve any CyR reached OS of 71%. Obtaining a MCyR at 3–12 m resulted in >90% OS. Duration of MCyR was longer in Pts who responded within 3m, than in the other groups. The results will be updated for the meeting including 60-m data up to 31-July-05. Figure Figure