Dear Editor,
I have read with great interest the paper by Saydam et al. [Citation1], reporting results of a company sponsored multicenter study from Turkey which evaluated the efficacy and safety of nilotinib 300 mg twice daily among 112 patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP). The cumulative rates of complete cytogenetic (CCyR) and major molecular responses (MMR) by 12 months were 89% and 66%, respectively, and the rate of deep molecular response (DMR) was 22% [Citation1]. Fifteen patients quit tyrosine kinase inhibitor (TKI) treatment mainly due to adverse events, and one patient progressed to advanced disease and two patients died due to myocardial infarction.
Although the authors once again (but for the first time among Turkish patients) demonstrated that frontline treatment with nilotinib was effective and tolerable in patients with CML-CP, there are some points which need to be clarified.
The authors stated that they included patients who were diagnosed within 6 months prior to study entry, and no treatments were allowed other than anagrelide, hydroxyurea, and short-term imatinib. However, the authors did not give any details regarding these prior treatment modalities and the time from diagnosis to nilotinib initiation and their impact on response rates.
Moreover as stated by the authors, in the 300 mg twice daily arm of Evaluating Nilotinib Efficacy and Safety in Clinical Trials-Newly Diagnosed Patients (ENESTnd) study [Citation2], the rates of MMR and CCyR by 12 months were inferior compared with those of the present study; this was attributed to the higher proportion of patients with low Sokal risk scores in this study [Citation1] when compared with ENESTnd [Citation2]. I was wondering whether the defined response rates in the present study differ between different Sokal risk groups or not.
It is known that second-generation TKIs (2GTKIs) induce faster and deeper responses than imatinib [Citation3], and Saydam and colleagues [Citation1] clearly showed that most of the patients (80%) achieved BCR-ABL1IS ≤ 10% at 3 months. Where CCyR, MMR, and DMR rates at given time points different between patients with BCR-ABL1IS ≤ 10% and > 10% at 3 months in this study?
Although not indicated in the methods section, was nilotinib dose escalation (300 mg →; 400 mg) allowed in patients with treatment failure and did these patients benefit from this treatment modification?
2GTKIs are more potent than imatinib, and nilotinib can be a reasonable option in the treatment of patients with CML-CP in the upfront setting. As being the first study conducted among Turkish patients with CML-CP receiving frontline nilotinib, this study is very valuable and it displays comparable results as shown in the previous studies regarding efficacy and safety of nilotinib.
Declaration of interest
AE Eskazan had received honoraria from Novartis and Bristol-Myers Squibb. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
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References
- Saydam G, Haznedaroglu IC, Kaynar L, et al. Outcomes with frontline nilotinib treatment in Turkish patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase. Expert Opin Pharmacother. 2016;17(14):1851–1858.
- Saglio G, Kim DW, Issaragrisil S, et al. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med. 2010;362(24):2251–2259.
- Baccarani M, Deininger MW, Rosti G, et al. European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. Blood. 2013;122(6):872–884.