Dasatinib, Nilotinib Safe and Effective in CML Patients With Renal, Liver Dysfunction

March 12, 2016
Dave Levitan

Patients with chronic phase CML and pre-existing mild to moderate liver and/or renal dysfunction can be safely treated with frontline nilotinib or dasatinib, according to a new study.

Patients with chronic phase chronic myeloid leukemia (CML) and pre-existing mild to moderate liver and/or renal dysfunction can be safely treated with frontline nilotinib or dasatinib, according to a new study. Response rates were similar to CML patients without any organ dysfunction.

“Although both drugs are generally well tolerated, both can cause various hematologic and nonhematologic adverse events” that can be related to kidney and liver function, wrote study authors led by Jorge Cortes, MD, of the University of Texas MD Anderson Cancer Center in Houston. The major randomized trials of nilotinib and dasatinib, ENESTnd and DASISION, both required adequate renal and liver function, but patients often present at diagnosis of CML with some degree of dysfunction.

To test whether these agents are safe and effective in such patients, the researchers analyzed results from 215 consecutive patients (108 nilotinib, 107 dasatinib patients) with or without mild to moderate renal and/or liver dysfunction enrolled in phase II clinical trials at one center between 2005 and 2012. The results were published in the March issue of Clinical Lymphoma, Myeloma, & Leukemia.

At baseline, 6 dasatinib-treated patients (6%) had mild renal dysfunction and 13 (12%) had mild liver dysfunction, while 8 nilotinib patients (7%) had mild renal dysfunction, 1 (1%) had moderate renal dysfunction, and 9 (8%) had mild liver dysfunction. The median follow-up period was 49 months.

Over that period, no differences were seen with regard to response rates. In the full cohort, 93% of patients with no organ dysfunction had a complete cytogenetic response, compared with 91% of those with liver dysfunction (P = .670) and 87% of those with renal dysfunction (P = .324).

A total of 86% of normal-function patients achieved a major molecular response, compared with 86% of those with liver dysfunction (P = 1.000) and 80% of those with renal dysfunction (P = .472). And finally, 69% of those with normal organ function achieved an MR4.5 response, compared with 64% of liver dysfunction patients (P = .617) and 60% of renal dysfunction patients (P = .565).

Failure-free, event-free, and treatment-failure survival rates at 4 years were similar between those with and without organ dysfunction in both nilotinib and dasatinib groups. Those with renal dysfunction did have significantly worse 4-year overall survival compared with normal organ function patients (94% normal vs 90% renal dysfunction; P = .012).

Adverse events were generally similar, but those with renal dysfunction treated with either drug were more likely to have transient reversible acute kidney injury. Nilotinib-treated patients with renal dysfunction were also more likely to have bleeding.

The study was limited by the small number of patients with organ dysfunction included, as well as its retrospective design. Still, the authors concluded that “most patients with mild liver dysfunction or mild or moderate renal dysfunction can be safely treated with dasatinib or nilotinib.” Further research is still needed in patients with more significant organ dysfunction.