Appeal type: Medical Necessity
Decision: Upheld Decision of Health Plan

Nature of Statutory Criteria/Case Summary: An enrollee has requested the medication Iclusig (ponatinib) HCl tablet 15 mg for treatment of the enrollees B-cell acute lymphocytic leukemia (BCR-ABL), Philadelphia chromosome-positive. Findings: The physician reviwer found that the submitted documentation fails to demonstrate the medical necessity for the requested medication in this clinical setting. The decision to change therapy from Dasatinib to Iclusig (ponatinib) was based on the treating providers assessment that Dasatinib was a treatment failure (resistance). However, according to the records, this patient was actually responding well to Dasatinib and did not exhibit signs of resistance. The medical record noted that the BCR-ABL had gradually decreased from a 5.2 log to 0.09 log. When the BCR-ABL gradually decreases, this is an indicator that the patient is responding and may be on the right track. Thus, the record noting the gradual decrease is considered a good response and does not constitute resistance or treatment failure.  In an article by Baccarani and colleagues they state the following, Resistance to tyrosine kinase inhibitors (TKIs) has many facets. The causes of resistance include low patient compliance, low plasma or intracellular drug concentration, BCR-ABL1 mutations, and clonal chromosome abnormalities in Ph+ cells, but in at least 50% of patients the causes are currently unknown. Primary resistance occurs when a predefined response level is not achieved within a pre-specified period of time. Not achieving a complete hematologic response (CHR) within 3 months, not achieving a partial cytogenetic response and/or a BCR-ABL1 transcripts level 10% (international standard) within 6 months, and not achieving a complete cytogenetic response (CCyR) and/or a BCR-ABL1 transcripts level <1% within 12 months, define primary resistance. Secondary resistance is defined by a loss of CHR, or CCyR, or major molecular response. Moreover, in a study by Shamroe and Comeau, the authors concluded that Iclusig (ponatinib) is a potent tyrosine kinase inhibitors (TKI) that can overcome several resistance mechanisms in previously treated patients with chronic myelogenous leukemia and Ph+ ALL, as in this patient. This same study recommends that Iclusig (ponatinib) should be reserved for patients who have failed first-line therapy, have the T315I mutation, or have progressed. The submitted documentation does not show that this patient had failed first-line therapy or that he progressed. Instead, the records show this patient was responding well to Dasatinib, was tolerant to the drug and did not need a switch to another TKI. The patient was gradually showing continuous log reductions in his BCR-ABL level over time an indication that he was responding. All told, the requested Iclusig (ponatinib) HCl tablet 15 mg is not medically necessary for the treatment of this patient.Final Result: The reviewer determined that the requested medication is not medically necessary for treatment of the patients medical condition. Therefore, the Health Plans denial should be upheld.Credentials/Qualifications: The reviewer is board certified in internal medicine and is actively practicing. The reviewer is an expert in the treatment of the enrollees medical condition and knowledgeable about the proposed treatment through recent or current actual clinical experience treating those with the same or a similar medical condition.