Efficacy and Safety of Ibrutinib Therapy in Patients with Chronic Lymphocytic Leukemia: Retrospective Analysis of Real-Life DataAnıl Tombak1, Funda Pepedil Tanrıkulu2, Salih Sertaç Durusoy3, Hüseyin Derya Dinçyürek4, Emin Kaya5, Elif Gülsüm Ümit6, İrfan Yavaşoğlu7, Özgür Mehtap8, Burak Deveci9, Mehmet Ali Özcan10, Hatice Terzi11, Müfide Okay12, Nilgün Sayınalp12, Mehmet Yılmaz3, Vahap Okan3, Alperen Kızıklı3, Ömer Özcan13, Güven Çetin13, Sinan Demircioğlu14, İsmet Aydoğdu15, Güray Saydam16, Eren Arslan Davulcu16, Gül İlhan17, Mehmet Ali Uçar18, Gülsüm Özet18, Seval Akpınar19, Burhan Turgut19, İlhami Berber5, Erdal Kurtoğlu20, Mehmet Sönmez21, Derya Selim Batur21, Rahşan Yıldırım22, Vildan Özkocaman23, Ahmet Kürşad Güneş24, Birsen Sahip25, Şehmus Ertop25, Olga Meltem Akay26, Abdülkadir Baştürk27, Mehmet Hilmi Doğu28, Aydan Akdeniz1, Ali Ünal29, Ahmet Seyhanlı30, Emel Gürkan4, Demet Çekdemir31, Burhan Ferhanoğlu321Mersin University Faculty of Medicine, Department of Internal Medicine, Division of Hematology, Mersin, Turkey
2Başkent University Adana Application and Research Center, Adana, Turkey
3Gaziantep University Faculty of Medicine, Department of Hematology, Gaziantep, Turkey
4Çukurova University Faculty of Medicine, Department of Hematology, Adana, Turkey
5İnönü University Turgut Özal Medical Center, Department of Hematology, Malatya, Turkey
6Trakya University Faculty of Medicine, Department of Hematology, Edirne, Turkey
7Adnan Menderes Univercity Faculty of Medicine, Department of Hematology, Aydın, Turkey
8Kocaeli University Faculty of Medicine,Department of Hematology, Kocaeli, Turkey
9Medstar Antalya Hospital, Clinic of Hematology, Antalya, Turkey
10Dokuz Eylül University Faculty of Medicine, Department of Hematology, İzmir, Turkey
11Cumhuriyet University Faculty of Medicine, Department of Hematology, Sivas, Turkey
12Hacettepe University Faculty of Medicine, Department of Internal Medicine, Division of Hematology, Ankara, Turkey
13Bezmialem Vakıf University Faculty of Medicine, Department of Hematology, İstanbul, Turkey
14Necmettin Erbakan University Meram Faculty of Medicine, Department of Hematology, Konya, Turkey
15Celal Bayar University Faculty of Medicine, Department of Hematology, Manisa, Turkey
16Ege University Hospital, Clinic of Internal Medicine, Division of Hematology İzmir, Turkey
17Mustafa Kemal University Faculty of Medicine, Department of Internal Medicine, Hatay, Turkey
18Ankara Numune Training and Research Hospital, Clinic of Hematology, Ankara, Turkey
19Namık Kemal University Faculty of Medicine, Department of Hematology, Tekirdağ, Turkey
20Antalya Training and Research Hospital, Clinic of Hematology, Antalya, Turkey
21Karadeniz Technical University Faculty of Medicine, Department of Hematology, Trabzon, Turkey
22Ataturk University Faculty of Medicine, Department of Hematology, Erzurum, Turkey
23Uludağ University Faculty of Medicine, Division of Hematology, Bursa, Turkey
24Şanlıurfa Mehmet Akif İnan Training and Research Hospital, Clinic of Hematology, Şanlıurfa, Turkey
25Zonguldak Bülent Ecevit University Faculty of Medicine, Department of Hematology, Zonguldak, Turkey
26Koç University Faculty of Medicine, Department of Hematology, İstanbul, Turkey
27Konya Training and Research Hospital, Clinic of Internal Medicine, Konya, Turkey
28İstanbul Training and Research Hospital, Clinic of Hematology, İstanbul, Turkey
29Erciyes University Faculty of Medicine, Department of Internal Medicine, Kayseri, Turkey
30Ege University Faculty of Medicine, Department of Hematology, İzmir, Turkey
31Anadolu Medical Center, Bone Marrow Transplantation Center, Department of Hematology, Kocaeli, Turkey
32İstanbul University-Cerrahpaşa Cerrahpaşa Faculty of Medicine, Department of Internal Medicine Section of Haematology, İstanbul, Turkey
Objective: This study aimed to retrospectively evaluate the efficacy, safety, and survival outcome of single-agent ibrutinib therapy in chronic lymphocytic leukemia patients.
Materials and Methods: A total of 136 patients (mean age ± standard deviation: 64.6±10.3 years, 66.9% males) who had received at least one dose of ibrutinib were included in this retrospective multicenter, noninterventional hospital-registry study conducted at 33 centers across Turkey. Data on patient demographics, baseline characteristics, laboratory findings, and leukemia-cell cytogenetics were retrieved. Treatment response, survival outcome including overall survival (OS) and progression-free survival (PFS), and safety data were analyzed.
Results: Overall, 36.7% of patients were categorized as Eastern Cooperative Oncology Group (ECOG) class 2-3, while 44.9% were in Rai stage 4. Fluorescence in situ hybridization revealed the presence of del(17p) in 39.8% of the patients. Patients received a median of 2.0 (range: 0-7) lines of pre-ibrutinib therapy. Median duration of therapy was 8.8 months (range: 0.4-58.0 months). The 1-year PFS and OS rates were 82.2% and 84.6%, respectively, while median PFS time was 30.0 (standard error, 95% confidence interval: 5.1, 20.0-40.0) months and median OS time was 37.9 (3.2, 31.5-44.2) months. Treatment response (complete or partial response), PFS time, and OS time were better with 0-2 lines versus 3-7 lines of prior therapy (p<0.001, p=0.001, and p<0.001, respectively), with ECOG class 0-1 versus class 2-3 (p=0.006, p=0.011, and p=0.001, respectively), and with Rai stage 0-2 versus 3-4 (p=0.002, p=0.001, and p=0.002, respectively). No significant difference was noted in treatment response rates or survival outcome with respect to the presence of comorbidity, bulky disease, or del(17p). While 176 adverse events (AEs) were reported in 74 (54.4%) patients, 46 of those 176 AEs were grade 3-4, including pneumonia (n=12), neutropenia (n=11), anemia (n=5), thrombocytopenia (n=5), and fever (n=5).
Conclusion: This real-life analysis confirms the favorable efficacy and safety profile of long-term ibrutinib treatment while emphasizing the potential adverse impacts of poorer ECOG performance status, heavy treatment prior to ibrutinib, and advanced Rai stage on patient compliance, treatment response, and survival outcomes.
Keywords: lymphocytic leukemia, Ibrutinib, Bruton’s tyrosine kinase inhibitor
Kronik Lenfositik Lösemili Hastalarda İbrutinib Tedavisinin Etkililiği ve Güvenilirliği: Gerçek Hayat Verilerinin Retrospektif AnaliziAnıl Tombak1, Funda Pepedil Tanrıkulu2, Salih Sertaç Durusoy3, Hüseyin Derya Dinçyürek4, Emin Kaya5, Elif Gülsüm Ümit6, İrfan Yavaşoğlu7, Özgür Mehtap8, Burak Deveci9, Mehmet Ali Özcan10, Hatice Terzi11, Müfide Okay12, Nilgün Sayınalp12, Mehmet Yılmaz3, Vahap Okan3, Alperen Kızıklı3, Ömer Özcan13, Güven Çetin13, Sinan Demircioğlu14, İsmet Aydoğdu15, Güray Saydam16, Eren Arslan Davulcu16, Gül İlhan17, Mehmet Ali Uçar18, Gülsüm Özet18, Seval Akpınar19, Burhan Turgut19, İlhami Berber5, Erdal Kurtoğlu20, Mehmet Sönmez21, Derya Selim Batur21, Rahşan Yıldırım22, Vildan Özkocaman23, Ahmet Kürşad Güneş24, Birsen Sahip25, Şehmus Ertop25, Olga Meltem Akay26, Abdülkadir Baştürk27, Mehmet Hilmi Doğu28, Aydan Akdeniz1, Ali Ünal29, Ahmet Seyhanlı30, Emel Gürkan4, Demet Çekdemir31, Burhan Ferhanoğlu321Mersin University Faculty of Medicine, Department of Internal Medicine, Division of Hematology, Mersin, Turkey
2Başkent University Adana Application and Research Center, Adana, Turkey
3Gaziantep University Faculty of Medicine, Department of Hematology, Gaziantep, Turkey
4Çukurova University Faculty of Medicine, Department of Hematology, Adana, Turkey
5İnönü University Turgut Özal Medical Center, Department of Hematology, Malatya, Turkey
6Trakya University Faculty of Medicine, Department of Hematology, Edirne, Turkey
7Adnan Menderes Univercity Faculty of Medicine, Department of Hematology, Aydın, Turkey
8Kocaeli University Faculty of Medicine,Department of Hematology, Kocaeli, Turkey
9Medstar Antalya Hospital, Clinic of Hematology, Antalya, Turkey
10Dokuz Eylül University Faculty of Medicine, Department of Hematology, İzmir, Turkey
11Cumhuriyet University Faculty of Medicine, Department of Hematology, Sivas, Turkey
12Hacettepe University Faculty of Medicine, Department of Internal Medicine, Division of Hematology, Ankara, Turkey
13Bezmialem Vakıf University Faculty of Medicine, Department of Hematology, İstanbul, Turkey
14Necmettin Erbakan University Meram Faculty of Medicine, Department of Hematology, Konya, Turkey
15Celal Bayar University Faculty of Medicine, Department of Hematology, Manisa, Turkey
16Ege University Hospital, Clinic of Internal Medicine, Division of Hematology İzmir, Turkey
17Mustafa Kemal University Faculty of Medicine, Department of Internal Medicine, Hatay, Turkey
18Ankara Numune Training and Research Hospital, Clinic of Hematology, Ankara, Turkey
19Namık Kemal University Faculty of Medicine, Department of Hematology, Tekirdağ, Turkey
20Antalya Training and Research Hospital, Clinic of Hematology, Antalya, Turkey
21Karadeniz Technical University Faculty of Medicine, Department of Hematology, Trabzon, Turkey
22Ataturk University Faculty of Medicine, Department of Hematology, Erzurum, Turkey
23Uludağ University Faculty of Medicine, Division of Hematology, Bursa, Turkey
24Şanlıurfa Mehmet Akif İnan Training and Research Hospital, Clinic of Hematology, Şanlıurfa, Turkey
25Zonguldak Bülent Ecevit University Faculty of Medicine, Department of Hematology, Zonguldak, Turkey
26Koç University Faculty of Medicine, Department of Hematology, İstanbul, Turkey
27Konya Training and Research Hospital, Clinic of Internal Medicine, Konya, Turkey
28İstanbul Training and Research Hospital, Clinic of Hematology, İstanbul, Turkey
29Erciyes University Faculty of Medicine, Department of Internal Medicine, Kayseri, Turkey
30Ege University Faculty of Medicine, Department of Hematology, İzmir, Turkey
31Anadolu Medical Center, Bone Marrow Transplantation Center, Department of Hematology, Kocaeli, Turkey
32İstanbul University-Cerrahpaşa Cerrahpaşa Faculty of Medicine, Department of Internal Medicine Section of Haematology, İstanbul, Turkey
Amaç: Kronik lenfositik lösemi hastalarında tek ajan ibrutinib tedavisinin etkinliğini, güvenliğini ve sağkalım sonuçlarını geriye dönük olarak değerlendirmek.
Gereç ve Yöntem: Otuz üç merkezde yapılan bu retrospektif, çok merkezli, girişimsel olmayan hastane kayıt çalışmasına en az bir doz ibrutinib uygulanan 136 hasta (ortalama ± standart sapma yaş 64,6 10,3, % 66,9’u erkek) dahil edildi. Hastaların demografik verileri, bazal karakteristikleri, laboratuvar bulguları, lösemi hücre sitogenetiği ile ilgili veriler kaydedildi. Tedavi yanıtı, genel sağkalım (OS), progresyonsuz sağkalım (PFS) ve güvenlik verileri analiz edildi.
Bulgular: Hastaların %36,7’sinde ECOG 2-3, % 44,9’u Rai evre 4 idi. FISH ile hastaların %39,8’inde del(17p) varlığını gösterdi. Hastalar medyan 2 (0 ila 7 arasında) sıra pre-ibrutinib tedavisi aldı. Medyan tedavi süresi 8,8 aydı (0,4-58 ay). Bir yıllık PFS ve OS oranları sırasıyla %82,2 ve %84,6, medyan (SE, %95 güven aralığı) PFS süresi 30 (5,1, 20-40) ay ve OS süresi 37,9 (3,2, 31,5-44,2) aydı. Tedavi yanıtı (CR veya PR), PFS ve OS süreleri; ibrutinib öncesi 3-7 basamak tedaviye karşı 0-2 basamak tedavi alanlarda (p<0,001, p=0,001 ve p<0,001, sırayla), ECOG 2-3’e göre ECOG 0-2 olanlarda (p=0,006, p=0,011 ve p=0,001, sırasıyla), Rai evre 0-2 olanlarda Rai evre 3-4 olanlara göre (p=0,002, p=0,001 and p=0,002, sırasıyla) daha iyiydi. Komorbidite, hacimli hastalık veya del(17p) varlığına göre tedaviye yanıt oranlarında veya sağkalım sonuçlarında önemli bir fark kaydedilmedi. 74 hastada (%54,4) 176 advers olay (AE) saptandı; 176 AE’nin 46’sı derece 3-4 idi. Bunlar; pnömoni (n=12), nötropeni (n=11), anemi (n=5), trombositopeni (n=5) ve ateş (n=5) idi.
Sonuç: Bu gerçek hayat analizi, uzun vadeli ibrutinib tedavisinin olumlu etkililiğini ve güvenlik profilini doğrularken, kötü ECOG performans durumunun, ibrutinib’den önce ağır şekilde tedavi verilmiş olmasının ve ileri evre hastalığın, hasta uyumu, tedavi yanıtı ve sağkalım üzerindeki potansiyel olumsuz etkilerini ortaya koymuştur.
Anahtar Kelimeler: Kronik lenfosittik lösemi, İbrutinib, Bruton tirozin, kinaz inhibitörü
Anıl Tombak, Funda Pepedil Tanrıkulu, Salih Sertaç Durusoy, Hüseyin Derya Dinçyürek, Emin Kaya, Elif Gülsüm Ümit, İrfan Yavaşoğlu, Özgür Mehtap, Burak Deveci, Mehmet Ali Özcan, Hatice Terzi, Müfide Okay, Nilgün Sayınalp, Mehmet Yılmaz, Vahap Okan, Alperen Kızıklı, Ömer Özcan, Güven Çetin, Sinan Demircioğlu, İsmet Aydoğdu, Güray Saydam, Eren Arslan Davulcu, Gül İlhan, Mehmet Ali Uçar, Gülsüm Özet, Seval Akpınar, Burhan Turgut, İlhami Berber, Erdal Kurtoğlu, Mehmet Sönmez, Derya Selim Batur, Rahşan Yıldırım, Vildan Özkocaman, Ahmet Kürşad Güneş, Birsen Sahip, Şehmus Ertop, Olga Meltem Akay, Abdülkadir Baştürk, Mehmet Hilmi Doğu, Aydan Akdeniz, Ali Ünal, Ahmet Seyhanlı, Emel Gürkan, Demet Çekdemir, Burhan Ferhanoğlu. Efficacy and Safety of Ibrutinib Therapy in Patients with Chronic Lymphocytic Leukemia: Retrospective Analysis of Real-Life Data. Turk J Hematol. 2021; 38(4): 273-285
Corresponding Author: Anıl Tombak |
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