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CML molecular response sustainable after nilotinib cessation


Leukemia, February 2017; advance online publication

: Just over half of chronic phase chronic myeloid leukemia (CML-CP) patients with a sustained deep molecular response on frontline nilotinib are able to maintain that response for a prolonged period after stopping therapy, results from the ENESTfreedom study show.

The researchers describe this proportion as “clinically significant” and say that, when considered alongside the results from the ENESTnd trial, which showed higher rates of deep responses and sustained deep responses with nilotinib versus imatinib, “more patients may become eligible to stop treatment and sustain remission following frontline nilotinib therapy than following imatinib therapy.”

The single-arm, phase II ENESTfreedom trial included 215 patients with Philadelphia chromosome-positive CML-CP who achieved molecular response (MR)4.5 (BCR-ABL1IS ≤0.0032%) on first-line nilotinib and continued treatment for at least 2 years and a median of 43.5 months.

Of these, 190 patients sustained their MR4.5 during a mandatory 1-year nilotinib consolidation phase and were therefore eligible to stop nilotinib treatment and enter a treatment-free remission (TFR) phase.

At 48 weeks after stopping nilotinib, 98 (51.6%) patients continued to have at least a major molecular response (MMR; BCR-ABL1IS ≤0.1%), while 86 restarted nilotinib after loss of MMR, typically within 6 months of stopping nilotinib.

This highlights “the importance of frequent monitoring of patients who stop [tyrosine kinase inhibitor] therapy to ensure timely retreatment,” say Andreas Hochhaus (Universitä̈tsklinikum Jena, Germany) and co-authors of the study.

Indeed, 98.8% and 88.4% regained MMR and MR4.5, respectively, after reinitiating treatment.

The researchers report in Leukemia that no patient progressed to accelerated phase or blast crisis.

The any-grade adverse event rates among patients who entered TFR were 83.2% during the 1-year consolidation phase (grade 3–4; 13.7%) and 65.8% during the first 48 weeks of the TFR phase (grade 3–4; 11.1%).

A predefined analysis of musculoskeletal pain-related events showed that 24.7% of patients reported musculoskeletal pain, myalgia, pain in an extremity, arthralgia, bone pain, or spinal pain during the first 48 weeks of the TFR phase compared with 16.3% during the consolidation phase, which the researchers say is “consistent with prior reports of imatinib-treated patients.”

Hochhaus et al conclude: “Additional follow-up and analyses of TFR data in ENESTfreedom and other TFR studies will be needed to further evaluate the patient disease and treatment characteristics prior to stopping treatment that may be associated with maintaining TFR, as well as the long-term durability of TFR.”

By Laura Cowen, medwireNews reporter

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