Early TKI Responses Predict CML Survival, Especially With Dasatinib

Two studies presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting, held earlier this month in Chicago, show that early deep responses with tyrosine kinase inhibitors (TKIs) yield lasting positive outcomes in chronic myeloid leukemia (CML) patients, and that dasatinib offers a better chance at such responses over imatinib.

Previous work has already suggested that early cytogenetic and molecular responses can lead to good outcomes in CML. “Landmark analyses are limited for CML patients treated with multiple prior TKIs, and the association between deep, early responses and long-term outcomes is not well established,” wrote authors of one of the studies (abstract 7053) led by Martin C. Müller, MD, of the Universitätsmedizin Mannheim in Germany, in a poster presentation.

That study evaluated the impact of early response to ponatinib in heavily pretreated patients participating in the ongoing PACE trial. It included 267 patients, most of whom (61%) had been treated with at least three prior TKIs; most patients (61%) had developed resistance to dasatinib or nilotinib.

Among 97 patients who achieved a major cytogenetic response (MCyR) at 3 months, 82% were progression-free at 3 years; only 47% of those who did not achieve that landmark were progression-free at 3 years (P < .0001). This was similar for complete cytogenetic response (CCyR; P = .0002). The same was true for overall survival (OS), with a 90% rate among those who achieved MCyR and a 74% rate in those who did not (P = .0025), again similar for CCyR (P = .029).

The same results were seen for landmark responses at 6 and 12 months. Furthermore, lower BCR-ABL1 transcript levels at each of those time points was also associated with both progression-free survival (PFS) and OS at 3 years. The lowest levels (≤ 0.1%) at 3 months were associated with 97% PFS and OS rates at 3 years.

In the other study (abstract 7055), authors led by Neil P. Shah, MD, PhD, of the University of California, San Francisco School of Medicine, examined the impact of the EURO risk score on achievement of BCR-ABL1 ≤ 10% and ≤ 1% at 3 and 6 months, and on long-term outcomes, in the DASISION trial. The analysis included 235 patients treated with dasatinib and 239 treated with imatinib.

The study found that more dasatinib patients than imatinib patients achieved the lower transcript levels, and that most were able to achieve at least ≤ 10% at 3 months regardless of EURO score. Of those with a low EURO score, 91% of dasatinib and 73% of imatinib patients achieved the BCR-ABL1 milestone; for intermediate scores, 80% and 66% achieved it, and for high scores, 83% and 44% achieved it.

Patients who did achieve the lower transcript levels had better survival at 5 years. For low-risk patients, the OS rate was 97% for dasatinib patients with a transcript level ≤ 10%, compared with 86% for those with levels above 10%. For imatinib, these rates were 97% and 100%, though the latter represented only 22 patients. In intermediate- and high-risk patients, the OS rate was 95% with lower transcript levels and dasatinib treatment, and 87% with levels above 10%. In imatinib patients, these rates were 96% and 86%, respectively.

The authors concluded that dasatinib should be used in newly diagnosed patients with CML in all EURO risk score groups due to the ability to produce deep and early responses.