Second-Line TKIs Offer Expanded Treatment Options For Newly Diagnosed Patients With CML

Second generation tyrosine kinase inhibitor (TKI) therapies approved for first-line therapy of chronic myelogenous leukemia (CML) offer newly diagnosed patients an expanded range of treatment options, according to Susan O’Brien, MD, of The University of Texas MD Anderson Cancer Center and chair of the NCCN Guidelines™ for CML. Dr. O’Brien emphasized the considerable advances made in the treatment of CML during her presentation of the updated NCCN Guidelines for CML at the NCCN 16th Annual Conference on March 11, 2011.

The addition of nilotinib (Tasigna®, Novartis Oncology) and dasatinib (SPRYCEL®, Bristol-Myers Squibb) as primary treatment options for patients with CML are the most significant updates to the NCCN Guidelines for CML, noted Dr. O’Brien. The newly approved therapies join the current standard of care, imatinib (Gleevec®, Novartis Oncology) as frontline options for newly diagnosed patients.

“The development of imatinib revolutionized the treatment of CML, providing patients with a safe and effective treatment option associated with an excellent survival benefit,” said Dr. O’Brien.

However, in recent studies, dasatinib and nilotinib were associated with significantly higher response rates and reduction in the 12-month incidence of accelerated or blast phase in patients with CML. Subsequently, the FDA granted approval of dasatinib and nilotinib as a first line therapy for newly diagnosed patients with CML. Both drugs were previously reserved for use in patients with resistance or intolerance to prior therapy, including imatinib.

“For newly diagnosed patients, all three TKI’s recommended in the NCCN Guidelines are viable treatment options,” said Dr. O’Brien. “Selection of appropriate TKI therapy will depend on the stage of the disease, the agent’s side effect profile and its relative effectiveness against BCR-ABL mutations.”

In terms of monitoring response to therapy, Dr. O’Brien noted that complete cytogenetic response (CyCR) remains the gold standard, although patients who rapidly achieve a major molecular response (MMR) also have a low rate of relapse.

“Research has shown that patients who achieve a complete cytogenetic response live longer, whereas a molecular response has not been shown to improve survival. Patients who do not achieve a complete molecular response should not be considered to have failed treatment,” clarified Dr. O’Brien.

There are clinical trials currently underway to determine if complete molecular response offers hope for treatment discontinuation or may be helpful in predicting future risk of progression or relapse.

In addition to the newly approved therapies, there are also several agents in clinical trials with promising activity.

Dr. O’Brien touched upon two TKIs, including ponatinib (ARIAD Pharmaceuticals), which has demonstrated efficacy in treating patients with the treatment-resistant T3151 mutation, and bosutinib (Pfizer), which has shown efficacy as a first-, second-, and third-line treatment.

“Availability of more potent TKIs has widened the treatment options and, given the new agents in the pipeline, the outlook for patients with CML continues to look promising,” said Dr. O’Brien.

The NCCN Guidelines are developed and updated through an evidence-based process with explicit review of the scientific evidence integrated with expert judgment by multidisciplinary panels of expert physicians from NCCN Member Institutions.

Source: National Comprehensive Cancer Network

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