Mehmet BANKİR, Funda PEPEDİL TANRİKULU, Didar YANARDAĞ AÇIK

Kronik lenfositik lösemide tedavi yaklaşımları: Gerçek yaşam verisi

Amaç: Son yıllarda kronik lenfositik lösemili hastaların yönetiminde pek çok yeni ajan yer almaya başlamıştır. CD20’ye karşı geliştirilen antikorlara; ibrutinib, idelalisib ve venetoclax gibi farklı hedeflere yönelik yeni moleküllerin de eklenmesi ile tedavi algoritmaları hızla değişmiştir. Bu çalışmada, koronavirüs pandemisi öncesi merkezimizdeki kronik lenfositik lösemi tedavi yaklaşımlarının tespit edilmesi amaçlanmıştır. Yöntem: Merkezimizde 01 Ekim 2018 ile 31 Aralık 2019 tarihleri arasında kronik lenfositik lösemi tanısı ile takip edilmiş olan hastalar retrospektif olarak incelenmiştir. Takip ve tedavi verisine ulaşılabilen, 18 yaş ve üzerindeki tüm hastalar çalışmaya dahil edilmiştir. Tanısı kesinleşmemiş olgular, takibi merkezimiz dışında yapılanlar, takip ve tedavi verisine ulaşılamayan olgular ve tedavisi çalışma aralığından önce başlanmış olan hastalar çalışma dışı bırakılmıştır. Tüm datalar hastanemizde hasta takibi için kullanılmakta olan elektronik veri tabanından alınmıştır. Bulgular: Toplam 138 (85 erkek, 53 kadın) hasta çalışmaya dahil edilmiştir. Olguların yaş ortalaması 65 (35-88)’dir. Tedavi almış olan 28 olgu için ileri analizler yapılmıştır. Hastaların %64’ünde birinci basamak tedavi uygulanırken, %32’sinin relaps/refrakter kronik lenfositik lösemi nedeni ile tedavi almakta olduğu görülmüştür. Birinci basamakta en sık uygulanan protokoller bendamustin, rituximab (%39) ve fludarabin, siklofosfamid, rituximab (%33)’ dır. Relaps/refrakter hastalık için tedavi uygulanan hastalarda ise ibrutinib (%78) ve venetoclax (%22) kullanıldığı görülmüştür. Sonuç: Kronik lenfositik lösemili hastalarda birinci basamakta öncelikle rituximab içeren bir kemoimmunoterapi protokolünün tercih edildiği, relaps/refrakter hastaların tamamında ise hedefe yönelik yeni moleküllerin uygulandığı görülmüştür. Mevcut klinik pratiğimiz güncel kılavuzlara paralel olup, yeni moleküllerin geri ödeme koşullarının uygun olduğu tüm hastalarda tercih edilmiş olması, ilerleyen yıllarda kronik lenfositik lösemi tedavi protokollerimizde hedefe yönelik moleküllerin kemoterapinin yerini alacağını düşündürmektedir.

Anahtar Kelimeler:

Kronik lenfositik lösemi, tedavi, ilaçlar

Treatment approaches in chronic lymphocytic leukemia: Real life data

Aim: Many new agents have started to take place in the management of patients with chronic lymphocytic leukemia in recent years. Following the antibodies developed against CD20 and the new targeting molecules such as ibrutinib, idelalisib and venetoclax, treatment algorithms have changed rapidly. In this study, it was aimed to determine chronic lymphocytic leukemia treatment approaches in our center before the coronavirus pandemic. Method: Patients who were followed up with a diagnosis of chronic lymphocytic leukemia between October 01, 2018 and December 31, 2019 were analyzed retrospectively in our center. All adult patients aged 18 years and over, whose follow-up and treatment data were available, were included in the study. Patients, whose diagnosis was not confirmed, treatment was initiated before the study interval and who were followed at an external center, were excluded. All data were gathered from the electronic database used for patient follow-up in our hospital. Results: A total of 138 (85 men, 53 women) patients were included in the study. The mean age of the cases was 65 (35-88) years. Further analyzes were made for 28 cases who received treatment. Among these patients, 64% received first-line treatment, while 32% were treated for relapse/refractory disease. The most common protocols used in the first line were bendamustine, rituximab (39%) and fludarabine, cyclophosphamide, rituximab (33%). Considering relapsed /refractory disease ibrutinib (%78) and venetoclax (22%) were the drugs used. Conclusion: It was observed that a chemoimmunotherapy protocol containing rituximab was primarily preferred in the first line treatment of chronic lymphocytic leukemia and targeted new molecules were applied in all relapsed/refractory patients. Our algorithms were in line with the current guidelines. As the new molecules were preferred in all patients with suitable reimbursement conditions, we think that targeted molecules will replace chemotherapy in further time.

Keywords:

Chronic lymphocytic leukemia, treatment, drugs,

PDF

___

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394-424.
Hallek M, Cheson BD, Catovsky D, et al. iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL. Blood. 2018;131(25):2745-2760.
Rai KR, Sawitsky A, Cronkite EP, Chanana AD, Levy RN, Pasternack BS. Clinical staging of chronic lymphocytic leukemia. Blood. 1975;46(2):219-234.
Binet JL, Auquier A, Dighiero G, et al. A new prognostic classification of chronic lymphocytic leukemia derived from a multivariate survival analysis. Cancer. 1981;48(1):198-206.
Döhner H, Stilgenbauer S, Benner A, et al. Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med. 2000;343(26):1910-1916.
Byrd JC, Furman RR, Coutre SE, et al. Ibrutinib Treatment for First-Line and Relapsed/Refractory Chronic Lymphocytic Leukemia: Final Analysis of the Pivotal Phase Ib/II PCYC-1102 Study. Clin Cancer Res. 2020;26(15):3918-3927.
Burger JA, O'Brien S. Evolution of CLL treatment - from chemoimmunotherapy to targeted and individualized therapy. Nat Rev Clin Oncol. 2018;15(8):510-527.
Scarfò L, Ferreri AJ, Ghia P. Chronic lymphocytic leukaemia. Crit Rev Oncol Hematol. 2016; 104:169-182.
Hallek M, Fischer K, Fingerle-Rowson G, et al. German Chronic Lymphocytic Leukaemia Study Group. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet. 2010;376(9747):1164-1174.
Eichhorst B, Fink AM, Bahlo J, et al. German CLL Study Group (GCLLSG). First-line chemoimmunotherapy with bendamustine and rituximab versus fludarabine, cyclophosphamide, and rituximab in patients with advanced chronic lymphocytic leukaemia (CLL10): an international, open-label, randomised, phase 3, non-inferiority trial. Lancet Oncol. 2016;17(7):928-942.
Wierda WG, Byrd JC, Abramson JS, et al. Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Version 4.2020, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2020;18(2):185-217.
Harkins RA, Patel SP, Flowers CR. Cost-effectiveness of New Targeted Agents in the Treatment of Chronic Lymphocytic Leukemia. Cancer J. 2019;25(6):418-427.
Shanafelt TD, Wang XV, Kay NE, et al. Ibrutinib-Rituximab or Chemoimmunotherapy for Chronic Lymphocytic Leukemia. N Engl J Med. 2019;381(5):432-443.
Burger JA, Barr PM, Robak T, et al. Long-term efficacy and safety of first-line ibrutinib treatment for patients with CLL/SLL: 5 years of follow-up from the phase 3 RESONATE-2 study. Leukemia. 2020;34(3):787-798.
Byrd JC, Furman RR, Coutre SE, et al. Ibrutinib Treatment for First-Line and Relapsed/Refractory Chronic Lymphocytic Leukemia: Final Analysis of the Pivotal Phase Ib/II PCYC-1102 Study. Clin Cancer Res. 2020;26(15):3918-3927.
Ghia P, Pluta A, Wach M, et al. ASCEND: Phase III, Randomized Trial of Acalabrutinib Versus Idelalisib Plus Rituximab or Bendamustine Plus Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia. J Clin Oncol. 2020;38(25):2849-2861.
Sharman JP, Egyed M, Jurczak W, et al. Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzmab for treatment-naive chronic lymphocytic leukaemia (ELEVATE TN): a randomised, controlled, phase 3 trial. Lancet. 2020;395(10232):1278-1291.
Tam CS, Trotman J, Opat S, et al. Phase 1 study of the selective BTK inhibitor zanubrutinib in B-cell malignancies and safety and efficacy evaluation in CLL. Blood. 2019;134(11):851-859.
Roberts AW, Davids MS, Pagel JM, et al. Targeting BCL2 with Venetoclax in Relapsed Chronic Lymphocytic Leukemia. N Engl J Med. 2016;374(4):311-322.
Seymour JF, Kipps TJ, Eichhorst B, et al. Venetoclax-Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia. N Engl J Med. 2018;378(12):1107-1120.
Jones JA, Mato AR, Wierda WG, et al. Venetoclax for chronic lymphocytic leukaemia progressing after ibrutinib: an interim analysis of a multicentre, open-label, phase 2 trial. Lancet Oncol. 2018;19(1):65-75.
Hallek M. Chronic lymphocytic leukemia: 2020 update on diagnosis, risk stratification and treatment. Am J Hematol. 2019;94(11):1266-1287.