Failure to achieve a complete hematologic response at the time of a major cytogenetic response with second-generation tyrosine kinase inhibitors is associated with a poor prognosis among patients with chronic myeloid leukemia in accelerated or blast phase

Abstract

Second-generation tyrosine kinase inhibitors are effective in Philadelphia chromosome-positive (Ph(+)) acute lymphoblastic leukemia (ALL) and chronic myeloid leukemia (CML). Occasionally, patients with Ph(+) ALL, or accelerated phase (AP) or blast phase (BP) CML achieve a major cytogenetic response (MCyR) but not a complete hematologic response (CHR). We analyzed 126 patients with CML in AP or BP, or with Ph(+) ALL treated with dasatinib or nilotinib after imatinib failure. Twenty patients received sequential treatment with both dasatinib and nilotinib for a total of 146 instances. CHR and MCyR rates were 54% and 37%, respectively in AP, 17% and 39% in BP, and 33% and 50% in Ph+ ALL. Failure to achieve a CHR at the time of achievement of a MCyR was associated with an inferior outcome, similar to that of patients without a MCyR (2-year survival rate, 37% and 35%, respectively). In contrast, patients with MCyR and concomitant CHR had a 77% 2-year survival rate. Twelve of 29 patients with MCyR without concomitant CHR later achieved a CHR; the 2-year survival rate for these patients was 55% compared with 22% for those who never achieved a CHR. These results suggest that achievement of a MCyR without concomitant CHR is associated with poor outcome.

Figure 1

Overall survival by 3 groups. (A) Total population, (B) patients treated with dasatinib, and (C) patients treated with nilotinib. MCyR+CHRc indicates a MCyR plus a concomitant CHR; MCyR+no conc. CHR indicates a MCyR with no concomitant CHR. Censored cases are shown with vertical tick marks. P values were calculated by the log-rank test for heterogeneity.

Figure 2

Overall survival by 5 groups. MCyR+CHRc indicates a MCyR plus a concomitant CHR; MCyR+CHR nc indicates a MCyR with no concomitant CHR. Censored cases are shown with vertical tick marks. P values were calculated by the log-rank test for heterogeneity.