Chronic myeloid leukemia (CML) is a hematological malignancy that represents up to 20% of all leukemias in adults.1 The abnormal fusion of the BCR and ABL1 gene on chromosomes 22 and 9, respectively, is associated with CML. The BCR-ABL1 fusion protein leads to uncontrolled proliferation of granulocytes, which is the underlying pathophysiological process in CML.2 There are a multitude of treatment options for CML including tyrosine kinase inhibitors (TKIs; ie, dasatinib, nilotinib, imatinib) and older agents such as hydroxyurea, busulfan, and interferon alfa.

As more treatment options became available in CML, along with increasing research into the disease state, there are some clinical data to support a potential for increased risk of additional solid organ malignancies in patients with CML. This risk has yet to be fully elucidated and the underlying mechanism requires further clarification as to whether it could be a direct result of the medications used to treat CML or the disease itself.

TKIs are relatively well-tolerated medications with the most common adverse events including nausea, vomiting, diarrhea, edema, skin reactions, and muscle cramps.3 After several patients with CML who were treated with imatinib developed a second malignancy, Roy et al decided to retrospectively review the 189 patients that they had treated with imatinib to see if they could identify any potential risk factors or etiologies.  In doing so,  they identified 6 (3.1%) patients who developed a second malignancy while being treated with imatinib, all of whom had received prior interferon-based regimens.  The time to develop a second malignancy varied greatly from 33 to 110 months from CML diagnosis and from 8 to 36 months after starting imatinib therapy. The second malignancy was found in the prostate (3), bladder (1), colon (1) and squamous cell carcinoma of an unknown primary site (1).

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These results prompted Novartis, the company who was manufacturing imatinib, to review their database to further identify any patients who developed a second primary malignancy while being treated with imatinib.4 The authors reported 110 malignancies reported from Novartis-sponsored clinical trials of imatinib up to May 2005. When using this information to calculate standardized incidence ratios (SIRs), they found an SIR of 0.87 (95% CI 0.69-1.08) for all cancers in their database which they noted as similar to what is expected in the general population.