NCCN greenlights nilotinib for imatinib-resistant CML patients

May 2, 2008

The NCCN has added nilotinib to its practice guideline for CML for use after any imatinib failure point in the chronic phase of disease.

The National Comprehensive Cancer Network has added nilotinib (Tasigna) to its practice guideline for the management of chronic myelogenous leukemia. NCCN CML panel members recommend that the tyrosine kinase inhibitor be considered after any imatinib (Gleevec) failure point in the chronic phase of disease. The NCCN panel also suggested that the drug be considered during accelerated phase or post-hematopoietic stem cell transplantation (HSCT), but emphasized that it should not be used during blast crisis.

Tasigna was approved by the FDA in October 2007 for the treatment of chronic-phase and accelerated-phase Ph+ CML in adult patients resistant to or intolerant of prior treatment that included imatinib.

Nilotinib is active against 32 of the 33 BCR-ABL mutations that are most commonly associated with imatinib resistance, according to Novartis, manufacturer of Tasigna and Gleevec.

The updated NCCN guideline (http://www.nccn.org/professionals/physician_gls/PDF/cml.pdf) includes the following recommendations:

• For CML patients after 3-month evaluation, nilotinib is advised for hematologic relapse but not for hematologic remission. After the 6-month evaluation, it may be used for patients with no cytogenetic response or cytogenetic relapse.

• For CML patients after 12-month evaluation, nilotinib is suggested for patients with no cytogenetic response or cytogenetic relapse; at 18 months, for patients with a partial, minor, or no cytogenetic response or cytogenetic relapse.

• For CML patients after HSCT, nilotinib is added as a treatment option for patients who are not in remission, or who are in relapse with graft-vs-host disease (GVHD), or in relapse with no GVHD and no complete cytogenetic response or PCR-positive after a complete cytogenetic response.

• For CML patients with disease progression on imatinib therapy, nilotinib is added as a treatment recommendation for patients in accelerated phase.

Based on multiple studies

The NCCN guideline was crafted based on multiple studies that assessed nilotinib in CML, including a major dose-escalation trial (N Engl J Med 354:2542-2551, 2006). In the second phase of that study, nilotinib 400 mg was administered orally twice daily to 280 patients with Ph+ CML in chronic phase after imatinib failure or intolerance. Patients had at least 6 months of follow-up.

According to the results, the estimated survival at 12 months was 95%, and adverse events were mostly mild to moderate (Blood 110:3540-3546, 2007). [See story above for updated results of the trial with 11-month follow-up.]