Although significantly fewer patients with ACAs had a complete cytogenetic response (CCyR) at 6 months, the percentage of patients who had a major molecular response (MMR) at 12 months — as well as the cumulative response rates — did not differ significantly. Failure-free survival, event-free survival, progression-free survival (PFS), and overall survival (OS) did not differ either. The authors concluded that “the presence of [ACAs] per se does not signal worse prognosis, at least in the chronic phase,” and that the highest risk ACAs are rarely present at diagnosis.
Yet the German CML Study IV, which specifically evaluated ACAs present at diagnosis, suggested that major route ACAs were associated with a worse prognosis than t(9;22), t(v;22), –Y, or other minor-route ACAs.
Patients with major route ACAs took longer to achieve CCyR and MMR and had shorter OS/PFS lengths. The 5-year OS rate among patients with major route ACAs was 53% vs 96% with minor-route ACAs, 91% with –Y, 87% with t(v;22), and 92% with t(9;22).
In clinical practice, foregoing cytogenetic evaluation at diagnosis would be controversial, partly because the new data are not consistent with those of the German CML IV study. Dr Mauro noted that “the German CML IV study, with a dataset twice as large and longer follow-up concludes something different — that major route ACAs seen at diagnosis have an impact on prognosis in CML.”
Other differences between Dr Alhuraiji’s study and the German CML IV study include the use of chemoimmunotherapy in the German study and the TKIs used: imatinib-based therapy was used in the German CML IV study while the other used various TKIs and doses, including 2 approaches without a front-line indication — 800 mg imatinib and ponatinib.
The fact that the study used “therapy choices not yet indicated (ponatinib) or not generally used (imatinib 800 mg) makes it controversial to apply the findings to general practice,” Dr Mauro added. “Practicing clinicians caring for patients with CML should consider these additional data in the overall weight they place on this point — additional chromosome anomalies at time of CML diagnosis — as the ‘jury may still be out’ on this issue.”
- NCCN clinical practice guidelines: chronic myeloid leukemia, version 2.2018. National Comprehensive Cancer Network website. Updated October 19, 2017. Accessed November 6, 2017.
- Fabarius A, Leitner A, Hochhaus A, et al. Impact of additional cytogenetic aberrations at diagnosis on prognosis of CML: long-term observation of 1151 patients from the randomized CML Study IV. Blood. 2011;118:6760-8.
- Wang W, Cortes JE, Tang G, et al. Risk stratification of chromosomal abnormalities in chronic myelogenous leukemia in the era of tyrosine kinase inhibitors. Blood. 2016;127:2742-50.
- Fabarius A, Kalmanti L, Dietz CT, et al. Impact of unbalanced minor route versus major route karyotypes at diagnosis on prognosis of CML. Ann Hematol. 2015;94:2015-24.
- Alhuraiji A, Kantarjian H, Boddu P, e tal. Prognostic significance of additional chromosomal abnormalities the time of diagnosis in patients with chronic myeloid leukemia treated with frontline tyrosine kinase inhibitors. Am J Hematol. 2017 Oct 13. doi: 10.1002/ajh.24943 [Epub ahead of print]