FDA Updates Nilotinib Label With Information on Discontinuing Treatment in Certain Patients With Early-Phase CML After Sustained Response

Key Points

Discontinuation in treatment a first in chronic myeloid leukemia

On December 22, the U.S. Food and Drug Administration (FDA) updated the product label for nilotinib (Tasigna) to include information for providers about how to discontinue the drug in certain patients. Nilotinib, first approved by the FDA in 2007, is indicated for the treatment of patients with Philadelphia chromosome–positive chronic myeloid leukemia (CML). With the updated dosing recommendations, patients with early (chronic) phase CML who have been taking nilotinib for 3 years or more—and whose leukemia has responded to treatment according to specific criteria as detected by a test that has received FDA marketing authorization—may be eligible to stop taking nilotinib.

“Patients diagnosed with CML generally face a lifetime of treatment to keep their leukemia from growing or recurring,” said Richard Pazdur, MD, Director of the FDA’s Oncology Center of Excellence and Acting Director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “[This] approval shows that some patients may be able to stop treatment with nilotinib altogether if they are showing a strong response to therapy. While we welcome this progress in patient care, it’s important to note that any discontinuation of treatment still means patients must be regularly monitored for disease recurrence.”

More on CML and Nilotinib

CML is a cancer of the bone marrow and causes the body to overproduce white blood cells. Almost all patients with CML have an abnormality known as the Philadelphia chromosome, which produces a protein called BCR-ABL. The National Cancer Institute at the National Institutes of Health estimates approximately 8,950 patients will be diagnosed with CML this year, and 1,080 will die of the disease.

Nilotinib is a kinase inhibitor that works in CML by blocking BCR-ABL, which promotes abnormal cell growth.

The FDA’s recent action adds information to the product label for patients and health-care providers regarding the conditions under which patients may be eligible to discontinue treatment, and notes that if treatment is stopped patients must be regularly monitored for disease recurrence.

Trial Evidence

The information about discontinuing nilotinib was based on two single-arm trials of patients with Philadelphia chromosome–positive chronic-phase CML. The trials measured how long patients were able to stop taking nilotinib without the leukemia returning (treatment-free remission [TFR]). In both trials, patients had to meet rigorous criteria showing how their cancer had responded to treatment before stopping nilotinib.

In the first trial, among the 190 newly diagnosed patients with CML who stopped nilotinib after taking it for 3 or more years and meeting other specified criteria, 51.6% were still in the TFR phase after approximately 1 year (48 weeks) and 48.9% were still in the TFR phase after approximately 2 years (96 weeks).

In the second trial, among the 126 patients who had stopped nilotinib after taking it for 3 or more years after switching from the cancer drug imatinib (Gleevec), 57.9% were still in the TFR phase after approximately 1 year (48 weeks) and 53.2% were still in the TFR phase after approximately 2 years (96 weeks).

An important part of both trials was regular and frequent monitoring of specific genetic information (RNA) that specifies the BCR-ABL protein level in the blood with a diagnostic test that has received FDA marketing authorization. Monitoring with a test able to detect reductions of specific RNA information with high accuracy and precision is critical to the safe discontinuation of nilotinib, as this monitoring provides the first signs of relapse.

Side Effects

Common side effects in patients who discontinued nilotinib include musculoskeletal symptoms such as body aches, bone pain, and pain in extremities. Some patients experienced prolonged musculoskeletal symptoms.

Common side effects of taking nilotinib include nausea; rash; headache; fatigue; pruritus; vomiting; diarrhea; cough; constipation; arthralgia; nasopharyngitis; pyrexia; night sweats; thrombocytopenia; myelosuppression; neutropenia; and anemia.

Severe side effects of taking nilotinib include myelosuppression; cardiac and arterial vascular occlusive events; pancreatitis and elevated serum lipase; hepatotoxicity; abnormal levels of electrolytes in the blood; tumor lysis syndrome; hemorrhage; drug interactions with CYP3A4 inhibitors; gastrectomy; and fluid retention. Women who are pregnant or breastfeeding should not take nilotinib because it may cause harm to a developing fetus or newborn baby.

Severe side effects typically associated with nilotinib administration occurred less frequently in patients who discontinued nilotinib. However, the long-term outcomes of patients discontinuing versus continuing treatment are unknown at this time.

Labeling and Label Update

The labeling for nilotinib contains a boxed warning to alert health-care professionals and patients about the risk of QT prolongation and sudden death. Nilotinib should not be taken by patients with hypokalemia, hypomagnesemia, or QT prolongation. Sudden deaths have been reported in patients taking nilotinib. The boxed warning also states nilotinib should not be given with drugs known to prolong the QT interval or with strong CYP3A4 inhibitors. Patients should not eat 2 hours prior to or 1 hour after taking nilotinib. 

The FDA granted the approval of the nilotinib label changes to Novartis Pharmaceuticals Corporation.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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