Kronik Faz KML Hastalarında Bosutinib Kullanımı: Tek Merkez Deneyimi

Öz

Kronik Myeloid Lösemide (KML), etyolojisinde sorumlu tirozin kinaz aktivitesi gösteren bcr-abl füzyon geninin keşfinden sonra, bu aktiviteyi inhibe eden ilaçların keşfiyle, daha uzun sağkalım sürelerine ulaşılabilmiştir. Bu ilaçlarla tedaviye zamanla direnç gelişmesi, ikinci ve üçüncü kuşak ajanların geliştirilmesinin önünü açmıştır. Bu çalışmamızda, merkezimizde ikinci kuşak tirozin kinaz inhibitörü (TKİ) – bosutinib - tedavisi alan hastaların, klinik, laboratuvar, moleküler yanıt, yan etki profili ve mortalite üzerindeki etkilerini değerlendirmeyi amaçladık. KML nedeniyle bosutinib tedavisi başlanan 17 hasta çalışmaya dahil edildi. Hastaların tedaviye kaçıncı sırada başlandığı, klinik, laboratuvar ve moleküler yanıt durumları retrospektif olarak elektronik hasta kayıtlarından tarandı. Elde edilen veriler hastaların ilaç başlanma sırasına göre karşılaştırıldı. İkinci (n=2), üçüncü (n=7) ve dördüncü (n=8) sırada bosutinib başlanan hastaların yaş, cinsiyet, komorbidite sayısı, bosutinib tedavi süresi açısından anlamlı bir fark gözlenmezken KML tanı yaşları arasında anlamlı bir farklılık mevcuttu. Moleküler yanıt ve yan etki profili açısından değerlendirildiğinde, ilacın başlanma sırası ile anlamlı bir farklılık yoktu. Hastaların genel sağkalımı 43,38 ± 4,98 ay (%95 GA: 33,62 – 53,16 ay) olarak gözlemlendi. Bosutinib tedavisinin her yaş grubunda, ilacın her başlanma sırasında kullanımının, stabil moleküler yanıt sağlaması açısından güvenli olduğu gözlemlendi. Yan etki profili açısından kullanımını sınırlayacak bir profile sahip olmaması nedeniyle KML tedavisinde tercih edilebilir bir molekül olarak düşünülmelidir.

Anahtar Kelimeler

• KML
• Bosutinib
• yan etki
• komorbidite

Use of Bosutinib in Patients With Chronic Phase Cml: A Single Center Experience

Öz

After the discovery of the bcr-abl fusion gene, which shows the tyrosine kinase activity responsible for its etiology in Chronic Myeloid Leukemia (CML), longer survival times have been achieved with the discovery of drugs that inhibit this activity. The development of resistance to treatment with these drugs over time paved the way for the development of second and third generation agents. In this study, we aimed to evaluate the effects of patients receiving second generation tyrosine kinase inhibitor (TKI) - bosutinib - treatment on clinical, laboratory, molecular response, side effect profile and mortality in our center. Seventeen patients who were started on bosutinib therapy for CML were included in the study. The order in which the treatment was initiated, the clinical, laboratory and molecular response status of the patients were retrospectively scanned from electronic patient records. The data obtained were compared according to the order of initiation of the drugs of the patients. While no significant difference was observed among the second-line (n=2), third-line (n=7) and fourth-line (n=8) bosutinib treated patients in terms of age, gender, number of comorbidities, and duration of bosutinib treatment, there was a significant difference between the ages of CML diagnosis. There was no significant difference with the order of initiation of the drug and molecular response and side effect profile. The overall survival of the patients was 43.38 ± 4.98 months (95% CI: 33.62 – 53.16 months). It was observed that the use of bosutinib treatment was safe in all age groups at each initiation order and provide a stable molecular response. Since it does not have a side-effect profile that would limit its use, it should be considered as a preferred molecule in CML treatment.

Anahtar Kelimeler

• CML
• Bosutinib
• side-effect
• comorbidity

Kaynakça

1. Hochhaus A, Baccarani M, Silver RT, Schiffer C, Apperley JF, Cervantes F, et al. European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia. Leukemia. 2020;34(4):966-84
2. Chereda B, Melo JV. Natural course and biology of CML. Ann Hematol. 2015;94 Suppl 2:S107-21
3. Pettit K, Rezazadeh A, Atallah EL, Radich J. Management of Myeloproliferative Neoplasms in the Molecular Era: From Research to Practice. American Society of Clinical Oncology Educational Book. 2022(42):1-19
4. Kota V, Brümmendorf TH, Gambacorti-Passerini C, Lipton JH, Kim D-W, An F, et al. Efficacy and safety following bosutinib dose reduction in patients with Philadelphia chromosome‒positive leukemias. Leukemia Research. 2021;111
5. Cortes JE, Gambacorti-Passerini C, Deininger MW, Mauro MJ, Chuah C, Kim DW, et al. Bosutinib Versus Imatinib for Newly Diagnosed Chronic Myeloid Leukemia: Results From the Randomized BFORE Trial. J Clin Oncol. 2018;36(3):231-7
6. Gambacorti‐Passerini C, Cortes JE, Lipton JH, Dmoszynska A, Wong RS, Rossiev V, et al. Safety of bosutinib versus imatinib in the phase 3 BELA trial in newly diagnosed chronic phase chronic myeloid leukemia. American Journal of Hematology. 2014;89(10):947-53
7. Baccarani M. Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood. 2006;108(6):1809-20
8. Brümmendorf TH, Cortes JE, Khoury HJ, Kantarjian HM, Kim DW, Schafhausen P, et al. Factors influencing long‐term efficacy and tolerability of bosutinib in chronic phase chronic myeloid leukaemia resistant or intolerant to imatinib. British Journal of Haematology. 2015;172(1):97-110

9. Claudiani S, Janssen JJWM, Byrne J, Smith G, Blijlevens N, Raghavan M, et al. A retrospective observational research study to describe the real‐world use of bosutinib in patients with chronic myeloid leukemia in the United Kingdom and the Netherlands. European Journal of Haematology. 2022;109(1):90-9
10. Khoury HJ, Gambacorti-Passerini C, Brümmendorf TH. Practical management of toxicities associated with bosutinib in patients with Philadelphia chromosome-positive chronic myeloid leukemia. Annals of Oncology. 2018;29(3):578-87