Advances in therapy of patients with chronic myelogenous leukemia

Abstract

Clinical trials suggest that patients treated up-front with second generation tyrosine kinase inhibitors (TKI) have increased chances for achieving rapid and deep molecular responses to therapy; this being a key criterion for discontinuation studies, thus reducing the risk of progression to accelerated phase or blast crisis as compared to imatinib. To date however, outcomes for all second generation TKIs are no different in overall survival than to imatinib. On the other hand administering ponatinib, a third generation TKI, demonstrates improved outcomes in patients resistant to other TKI therapies including those with the T315I ABL mutation, however this drug should be used with caution due to its toxicity profile and the risks of blood clots and occluded arteries and veins. Prospective trials suggest that TKI therapy may be safely and successfully discontinued leading to durable treatment-free remission (TFR) in a proportion of CML patients with deep and sustained molecular responses. Yet to be determined from ongoing studies, are the optimal durations of initial TKI therapy and deep molecular responses before TKI cessation, together with those biomarkers identifying patients with the highest chances of achieving prolonged TFR. Novel prognostic factors were found to be major-route, ‘additional cytogenic aberrations’ detected at diagnosis, reduced BCR/ABL1 transcript levels to < 10% at 3 months and to < 1% at 6 months along with the BCR/ABL1 transcript level halving time. Data analysis from cross linking patients from the Swedish CML register with the Swedish Cancer Register indicates that CML patients have a 50% increased risk of developing a second malignancy compared to a normal control population.