Original Article

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Blood Res 2020; 55(4):

Published online December 31, 2020

https://doi.org/10.5045/br.2020.2020158

© The Korean Society of Hematology

Safety and efficacy analysis of ibrutinib in 32 patients with CLL and various B-cell lymphomas: real-world data from a single-center study in Turkey

Mesut Göçer, Erdal Kurtoğlu

Department of Hematology, Antalya Training and Research Hospital, Antalya, Turkey

Correspondence to : Mesut Göçer, M.D.
Department of Hematology, Antalya Training and Research Hospital, Antalya 07055, Turkey
E-mail: gocermesut@gmail.com

Received: July 3, 2020; Revised: August 13, 2020; Accepted: October 8, 2020

Abstract

Background
Ibrutinib is an oral irreversible Bruton’s tyrosine kinase inhibitor. Here, we demonstrate the efficacy and safety of ibrutinib using real-life data from patients with marginal zone lymphoma (MZL), diffuse large B-cell lymphoma (DLBCL), Waldenström macroglobulinemia (WM), and follicular lymphoma (FL), especially in chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL).
Methods
This is a retrospective, observational, non-interventional, and single-center study on 32 patients who received ibrutinib treatment between January 2017 and March 2020 regardless of their diagnosis.
Results
Of the 32 patients, 11 had CLL and 21 had other B-cell lymphomas. Patients with CLL were prescribed ibrutinib for a median of 4 months (range, 2-18). In this group, diarrhea was observed in 3 (27.3%), pneumonia in 3 (27.3%), and thrombocytopenia and/or neutropenia in 2 (18.2%) patients. The overall response rate (ORR) was 85.6 % [28.5 % complete response (CR) and 57.1 % partial response (PR)] in the final response assessment during treatment with ibrutinib. Among other types of B-cell lymphoma, seven (33.4%) of the 21 patients were diagnosed with MCL, 5 (23.8%) with DLBCL, 4 (19.0%) with MZL, 3 (14.3%) with WM, and 2 (9.5%) with FL, upon follow-up. The median treatment duration was 4 months (range, 1-28) in this group. The most common adverse event was diarrhea: 8 (38.1%) patients. The ORR was 66.6% (20.0% CR and 46.6% PR) in the final response assessment during the treatment.
Conclusion
Ibrutinib is a good treatment option for CLL and other B-cell lymphomas, with an acceptable side effect profile, and high and promising CR/PR response rates. Ibrutinib treatment at an early stage decreases the burden of cytotoxic therapy in fragile patients, thereby, increasing their quality of life.

Keywords Ibrutinib, Bruton’s tyrosine kinase, B-cell lymphoma, Chronic lymphocytic leukemia

Article

Original Article

Blood Res 2020; 55(4): 206-212

Published online December 31, 2020 https://doi.org/10.5045/br.2020.2020158

Copyright © The Korean Society of Hematology.

Safety and efficacy analysis of ibrutinib in 32 patients with CLL and various B-cell lymphomas: real-world data from a single-center study in Turkey

Mesut Göçer, Erdal Kurtoğlu

Department of Hematology, Antalya Training and Research Hospital, Antalya, Turkey

Correspondence to:Mesut Göçer, M.D.
Department of Hematology, Antalya Training and Research Hospital, Antalya 07055, Turkey
E-mail: gocermesut@gmail.com

Received: July 3, 2020; Revised: August 13, 2020; Accepted: October 8, 2020

Abstract

Background
Ibrutinib is an oral irreversible Bruton’s tyrosine kinase inhibitor. Here, we demonstrate the efficacy and safety of ibrutinib using real-life data from patients with marginal zone lymphoma (MZL), diffuse large B-cell lymphoma (DLBCL), Waldenström macroglobulinemia (WM), and follicular lymphoma (FL), especially in chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL).
Methods
This is a retrospective, observational, non-interventional, and single-center study on 32 patients who received ibrutinib treatment between January 2017 and March 2020 regardless of their diagnosis.
Results
Of the 32 patients, 11 had CLL and 21 had other B-cell lymphomas. Patients with CLL were prescribed ibrutinib for a median of 4 months (range, 2-18). In this group, diarrhea was observed in 3 (27.3%), pneumonia in 3 (27.3%), and thrombocytopenia and/or neutropenia in 2 (18.2%) patients. The overall response rate (ORR) was 85.6 % [28.5 % complete response (CR) and 57.1 % partial response (PR)] in the final response assessment during treatment with ibrutinib. Among other types of B-cell lymphoma, seven (33.4%) of the 21 patients were diagnosed with MCL, 5 (23.8%) with DLBCL, 4 (19.0%) with MZL, 3 (14.3%) with WM, and 2 (9.5%) with FL, upon follow-up. The median treatment duration was 4 months (range, 1-28) in this group. The most common adverse event was diarrhea: 8 (38.1%) patients. The ORR was 66.6% (20.0% CR and 46.6% PR) in the final response assessment during the treatment.
Conclusion
Ibrutinib is a good treatment option for CLL and other B-cell lymphomas, with an acceptable side effect profile, and high and promising CR/PR response rates. Ibrutinib treatment at an early stage decreases the burden of cytotoxic therapy in fragile patients, thereby, increasing their quality of life.

Keywords: Ibrutinib, Bruton’s tyrosine kinase, B-cell lymphoma, Chronic lymphocytic leukemia

Fig 1.

Figure 1.Relationship between treatment duration and lymphocyte count.
Blood Research 2020; 55: 206-212https://doi.org/10.5045/br.2020.2020158

Fig 2.

Figure 2.Kaplan-Meier survival curves of overall survival based on del17p mutation in patients with CLL.
Blood Research 2020; 55: 206-212https://doi.org/10.5045/br.2020.2020158

Fig 3.

Figure 3.Kaplan-Meier survival curves of overall survival in patients with NHL.
Blood Research 2020; 55: 206-212https://doi.org/10.5045/br.2020.2020158

Table 1 . Demographic and clinical features of the patients with CLL..

Demographic and baseline clinical featuresN=11 (%)
Gender, female/male (%)4/7 (36.4/63.4)
Age, median (range)65 (51–80)
ECOG performance score≥3 1 (9.1)
Bulky lesion, N (%) 2 (18.2)
Rai stage≥3, N (%) 7 (63.6)
Del17p, N (%) 4 (36.4)
N of previous treatments
0–1 5 (45.5)
2–3 4 (36.4)
>3 2 (18.1)
Previous treatment regimens
R-FC 7 (63.6)
R-CVP 4 (36.4)
R-bendamustin 3 (27.3)
Chlorambucil 2 (18.2)
Other 4 (36.4)
Treatment duration with ibrutinib (mo, median) 4 (2–18)
Side effects of grade≥3 during treatment with ibrutinib 4 (36.4)
Treatment-emergent lymphocytosis, N (%) 0 (0.0)
Hb≤11 (g/dL), N (%) 6 (54.5)
Platelet≤100×109/L, N (%) 7 (63.6)
WBC (103/mL), mean (range)47,236 (1,300–182,900)
Absolute lymphocyte count (103/mL), mean (range)38,200 (300–166,200)

Table 2 . Incidence of adverse events (AEs) in patients with CLL and NHL..

CLLNHL
Hematologic AEsGrade 3–4, N (%)Any grade, N (%)Grade 3–4, N (%)Any grade, N (%)
Anemia0 (0)1 (9.1)0 (0)0 (0)
Thrombocytopenia0 (0)2 (18.1)1 (4.8)2 (9.5)
Neutropenia0 (0)2 (18.1)1 (4.8)1 (4.8)
Lymphocytosis0 (0)2 (18.1)0 (0)2 (9.5)
Non-hematologic AEs
Diarrhea1 (9.1)3 (27.3)2 (9.5)8 (38.1)
Pneumonia3 (27.3)3 (27.3)1 (4.8)5 (23.8)
Hemorrhage0 (0)1 (9.1)0 (0)0 (0)
Atrial fibrillation0 (0)0 (0)0 (0)0 (0)

Table 3 . Demographic and clinical features of patients with NHL..

Demographic and baseline clinical featuresN=21 (%)
Gender, female/male, N (%)9/12 (42.9/57.1)
Age, median (range) 69 (53–84)
Types of NHL
Mantle cell lymphoma, N (%) 7 (33.4)
Diffuse large B-cell lymphoma, N (%) 5 (23.8)
Marginal zone lymphoma, N (%) 4 (19.0)
Waldenström macroglobulinemia, N (%) 3 (14.3)
Follicular lymphoma, N (%) 2 (9.5)
High prognosis score, N (%) 14 (66.7)
ECOG performance score≥3, N (%) 8 (38.1)
Bulky lesion, N (%) 4 (19.0)
Ann Arbor stage≥3, N (%) 20 (95.2)
Presence of B symptoms, N (%) 10 (47.6)
N of previous treatments
1 9 (42.9)
2 9 (42.9)
3 3 (14.2)
Previous treatment regimens
R-CHOP/CHOP 20 (95.2)
R-bortezomib/bortezomib 5 (23.8)
R-CVP/CVP 3 (14.2)
Diğer 7 (33.4)
Treatment duration with ibrutinib, median (range) 4 (1–28)
Patient requiring dose reduction, N (%) 3 (14.3)
Side effect of grade≥3 during treatment with ibrutinib 5 (23.8)
Treatment-emergent lymphocytosis, N (%) 2 (9.5)
Hb (g/dL), median (range)11.8 (7.6–14.6)
Platelet (103/mL), median (range)165,000 (16,000–492,000)
WBC (103/mL), median (range)8,400 (3,200–157,800)
LDH U/L, median (range)257 (105–437)
Creatinine clearance (mL/min/1.73 m2), median (range) 64 (26–120)

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