UKALLXII/ECOG2993: addition of imatinib to a standard treatment regimen enhances long-term outcomes in Philadelphia positive acute lymphoblastic leukemia

Abstract

The Philadelphia chromosome positive arm of the UKALLXII/ECOG2993 study for adult acute lymphoblastic leukemia (ALL) enrolled 266 patients between 1993 and 2003 (pre-imatinib cohort). 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 complete remission (CR) rate was 92% in the imatinib cohort vs 82% in the preimatinib cohort (P = .004). At 4 years, the overall survival (OS) of all patients in the imatinib cohort was 38% vs 22% in the preimatinib cohort (P = .003). The magnitude of the difference between the preimatinib and imatinib cohorts in event-free survival (EFS), OS, and relapse-free survival (RFS) seen in univariate analysis was even greater in the multivariate analysis. In the preimatinib cohort, 31% of those starting treatment achieved hematopoietic stem cell transplant (alloHSCT) compared with 46% in the imatinib cohort. A Cox multivariate analysis taking alloHSCT into account showed a modest additional benefit to imatinib (hazard ratio for EFS = 0.64, 95% confidence interval 0.44-0.93, P = .02), but no significant benefit for OS and RFS. Adding imatinib to standard therapy improves CR rate and long-term OS for adults with ALL. A proportion of the OS benefit derives from the fact that imatinib facilitates alloHSCT. This trial was registered at clinicaltrials.gov as NCT00002514.

Figures

Figure 1

A flowchart of all patients entered into the Ph+ arm of UKALLXII/E2993.

Figure 2

Kaplan Meier plot of 10-year OS of all patients with Ph+ ALL by cohort. (A) Preimatinib vs imatinib. (B) Preimatinib vs late imatinib vs early imatinib.

Figure 3

A flowchart of postremission treatment. (A) Treatment received in the imatinib cohort. (B) Treatment received in the preimatinib cohort.

Figure 4

Kaplan Meier plot of 4-year OS in the imatinib cohort. Represents receipt of protocol myeloablative sibling/MUD alloHSCT, nonprotocol RIC alloHSCT, or no alloHSCT in patients who achieved CR on protocol and survived to day 84 (12 weeks), the earliest possible time of alloHSCT per protocol.

Figure 5

Kaplan Meier plot of 4-year OS in all patients with Ph+ ALL who did not receive alloHSCT, by preimatinib vs imatinib cohort.