What is the efficacy of imatinib for the treatment of Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (ALL)?

Updated: Jul 17, 2018
  • Author: Karen Seiter, MD; Chief Editor: Emmanuel C Besa, MD  more...
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Answer

In the German Multicenter ALL (GMALL) trial—a randomized study of imatinib versus standard induction therapy for patients older than 55 years with Ph+ ALL—the overall complete remission (CR) rate was 96.3% in patients assigned to imatinib and 50% in patients allocated to standard chemotherapy. [41] Severe adverse events were significantly more frequent during standard induction chemotherapy (90% vs 39%). The estimated overall survival of all patients was 42% at 24 months, with no significant difference between the 2 cohorts. [41]

The Ph+ arm of the UKALLXII/ECOG2993 study for adult ALL enrolled 266 patients between 1993 and 2003 (pre-imatinib cohort) [42] . In 2003, imatinib was introduced as a single-agent course following induction (N = 86, late imatinib). In 2005, imatinib was added to the second phase of induction (N = 89, early imatinib). The CR rate was 92% in the imatinib cohort vs 82% in the preimatinib cohort (P = .004). At 4 years, the overall survival of all patients in the imatinib cohort was 38% vs 22% in the preimatinib cohort (P = 0.003).

The CALGB 10001 trial studied whether the addition of imatinib to chemotherapy could improve the outcome of autologous transplantation in Ph+ ALL such that the results could be comparable to allogeneic transplantation. [43]  In this study of 58 patients, overall survival (median 6.0 years vs not reached) and disease-free survival (median 3.5 vs 4.1 years) were similar between those who underwent autologous and those who underwent allogeneic stem cell transplantation. The authors concluded that autologous stem cell transplantation represented an alternative to allogeneic stem cell transplantation in patients without sibling donors.

Several other studies have demonstrated improved outcomes with the addition of imatinib to chemotherapy. [44, 45, 46]


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