Ibrutinib in the Treatment of Refractory Chronic Lymphocytic Leukemia
Background & Aims. This paper presents the results of the observational study of ibrutinib in patients with chronic lymphocytic leukemia (CLL), conducted in SP Botkin Municipal Clinical Hospital. The main objective was the analysis of complications of ibrutinib and identification of factors, inf...
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| Language: | Russian |
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Practical Medicine Publishing House
2017-07-01
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| Series: | Клиническая онкогематология |
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| Online Access: | http://bloodjournal.ru/wp-content/uploads/2017/09/1.pdf |
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| author | EA Nikitin EA Dmitrieva MA Panteleev EI Emelina VL Ivanova YuB Kochkareva EG Arshanskaya IE Lazarev EE Markova LA Mukha NG Novitskaya MM Pankrashkina VV Glazunova AV Shubina SA Chernysh NK Khuazheva EV Naumova SA Lugovskaya ME Pochtar’ TN Obukhova OYu Vinogradova GE Gendlin VV Ptushkin |
| author_facet | EA Nikitin EA Dmitrieva MA Panteleev EI Emelina VL Ivanova YuB Kochkareva EG Arshanskaya IE Lazarev EE Markova LA Mukha NG Novitskaya MM Pankrashkina VV Glazunova AV Shubina SA Chernysh NK Khuazheva EV Naumova SA Lugovskaya ME Pochtar’ TN Obukhova OYu Vinogradova GE Gendlin VV Ptushkin |
| author_sort | EA Nikitin |
| collection | DOAJ |
| description | Background & Aims. This paper presents the results of the observational study of ibrutinib in patients with chronic lymphocytic leukemia (CLL), conducted in SP Botkin Municipal Clinical Hospital. The main objective was the analysis of complications of ibrutinib and identification of factors, influencing the dosage regimen; the secondary objective was the estimation of the total response to treatment, event-free and overall survival.
Materials & Methods. The study included 96 patients with CLL with indications for ibrutinib therapy. The median age was 64,9 years (range 32–91 years), the study population consisted of 69 (72 %) men and 27 (28 %) women. The condition of 25 (26 %) patients according to the ECOG scale was of > 3 points. The disease of stage C were diagnosed in 36 (37 %) patients . Deletion of 17p/TP53 mutations were detected in 29 (33 %) of 87 patients. Seventy patients had refractory CLL. The median of the number of the lines of the previous therapy was 3 (range 1–9). Adverse events were assessed in accordance with the CTCAE criteria, version 4.0; the bleeding severity was evaluated using ITP-specific bleeding score; hematological complications were classified according to the recommendations of IWCLL-2008.
Results. Ibrutinib was administered at a dosage of 420 mg per day daily until progression or intolerable toxicity. The median duration of ibrutinib therapy was 10.3 months. Ibrutinib was shown to have moderate toxicity, mostly of grade I or II. The bleeding was the most frequent complication. Of the hematological complications, thrombocytopenia was the most common (35 %); neutropenia < 1 × 109/L was observed in 4 patients. GIT complications were identified in 51 (53 %) patients. Atrial fibrillation was registered in 5 patients, who initially had sinus rhythm. The total of 144 infections were diagnosed in 64 (66 %) patients. Severe infections (> grade III) developed in 26 % of patients. The treatment response was assessed in 92 patients. The overall response to treatment was 89 %. Complete remission, partial remission and partial remission with lymphocytosis were achieved in 4 (4 %), 57 (62 %), and 21 (23 %) patients, respectively. The event-free survival and overall survival by the month 10 was 90 % and 91 %, respectively. For this observation period, ECOG status and the number of the lines of therapy prior to ibrutinib had the prognostic value.
Conclusion. Ibrutinib was shown to have high efficiency in relapsed/refractory forms of CLL. The nature of the ibrutinib toxicity is fundamentally different from that of the conventional chemotherapy. The frequency of ibrutinib therapy complications and patients’ non-compliance depends on the intensity of the previous treatment of CLL. Despite a short observation period, it can be concluded that ibrutinib had the greatest impact on the patient’s quality of life when administered for the first relapse. The low toxicity of ibrutinib is likely to allow the combination with other antitumor agents. |
| format | Article |
| id | doaj-art-b4cc495026834e6db9fdda699d68490c |
| institution | Kabale University |
| issn | 1997-6933 2500-2139 |
| language | Russian |
| publishDate | 2017-07-01 |
| publisher | Practical Medicine Publishing House |
| record_format | Article |
| series | Клиническая онкогематология |
| spelling | doaj-art-b4cc495026834e6db9fdda699d68490c2025-08-20T03:39:21ZrusPractical Medicine Publishing HouseКлиническая онкогематология1997-69332500-21392017-07-0110327128110.21320/2500-2139-2017-10-3-271-81Ibrutinib in the Treatment of Refractory Chronic Lymphocytic LeukemiaEA Nikitin0EA Dmitrieva1MA Panteleev2EI Emelina3VL Ivanova4YuB Kochkareva5EG Arshanskaya6IE Lazarev7EE Markova8LA Mukha9NG Novitskaya10MM Pankrashkina11VV Glazunova12AV Shubina13SA Chernysh14NK Khuazheva15EV Naumova16SA Lugovskaya17ME Pochtar’18TN Obukhova19OYu Vinogradova20GE Gendlin21VV Ptushkin22SP Botkin Municipal Clinical Hospital, 5 2-i Botkinskii pr-d, Moscow, Russian Federation, 125284SP Botkin Municipal Clinical Hospital, 5 2-i Botkinskii pr-d, Moscow, Russian Federation, 125284Dmitrii Rogachev Federal Scientific Clinical Centre of Pediatric Hematology, Oncology and Immunology, 1 Samory Mashela str., Moscow, Russian Federation, 117198NI Pirogov Russian National Research Medical University, 1 Ostrovityanova str., Moscow, Russian Federation, 117997SP Botkin Municipal Clinical Hospital, 5 2-i Botkinskii pr-d, Moscow, Russian Federation, 125284SP Botkin Municipal Clinical Hospital, 5 2-i Botkinskii pr-d, Moscow, Russian Federation, 125284SP Botkin Municipal Clinical Hospital, 5 2-i Botkinskii pr-d, Moscow, Russian Federation, 125284SP Botkin Municipal Clinical Hospital, 5 2-i Botkinskii pr-d, Moscow, Russian Federation, 125284SP Botkin Municipal Clinical Hospital, 5 2-i Botkinskii pr-d, Moscow, Russian Federation, 125284SP Botkin Municipal Clinical Hospital, 5 2-i Botkinskii pr-d, Moscow, Russian Federation, 125284SP Botkin Municipal Clinical Hospital, 5 2-i Botkinskii pr-d, Moscow, Russian Federation, 125284SP Botkin Municipal Clinical Hospital, 5 2-i Botkinskii pr-d, Moscow, Russian Federation, 125284SP Botkin Municipal Clinical Hospital, 5 2-i Botkinskii pr-d, Moscow, Russian Federation, 125284SP Botkin Municipal Clinical Hospital, 5 2-i Botkinskii pr-d, Moscow, Russian Federation, 125284SP Botkin Municipal Clinical Hospital, 5 2-i Botkinskii pr-d, Moscow, Russian Federation, 125284SP Botkin Municipal Clinical Hospital, 5 2-i Botkinskii pr-d, Moscow, Russian Federation, 125284Department of Clinical Laboratory Diagnostics, Russian Medical Academy of Postgraduate Education, 7 bld. 2 2-i Botkinskii pr-d, Moscow, Russian Federation, 125284Department of Clinical Laboratory Diagnostics, Russian Medical Academy of Postgraduate Education, 7 bld. 2 2-i Botkinskii pr-d, Moscow, Russian Federation, 125284Department of Clinical Laboratory Diagnostics, Russian Medical Academy of Postgraduate Education, 7 bld. 2 2-i Botkinskii pr-d, Moscow, Russian Federation, 125284Hematology Research Center, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167SP Botkin Municipal Clinical Hospital, 5 2-i Botkinskii pr-d, Moscow, Russian Federation, 125284NI Pirogov Russian National Research Medical University, 1 Ostrovityanova str., Moscow, Russian Federation, 117997SP Botkin Municipal Clinical Hospital, 5 2-i Botkinskii pr-d, Moscow, Russian Federation, 125284Background & Aims. This paper presents the results of the observational study of ibrutinib in patients with chronic lymphocytic leukemia (CLL), conducted in SP Botkin Municipal Clinical Hospital. The main objective was the analysis of complications of ibrutinib and identification of factors, influencing the dosage regimen; the secondary objective was the estimation of the total response to treatment, event-free and overall survival. Materials & Methods. The study included 96 patients with CLL with indications for ibrutinib therapy. The median age was 64,9 years (range 32–91 years), the study population consisted of 69 (72 %) men and 27 (28 %) women. The condition of 25 (26 %) patients according to the ECOG scale was of > 3 points. The disease of stage C were diagnosed in 36 (37 %) patients . Deletion of 17p/TP53 mutations were detected in 29 (33 %) of 87 patients. Seventy patients had refractory CLL. The median of the number of the lines of the previous therapy was 3 (range 1–9). Adverse events were assessed in accordance with the CTCAE criteria, version 4.0; the bleeding severity was evaluated using ITP-specific bleeding score; hematological complications were classified according to the recommendations of IWCLL-2008. Results. Ibrutinib was administered at a dosage of 420 mg per day daily until progression or intolerable toxicity. The median duration of ibrutinib therapy was 10.3 months. Ibrutinib was shown to have moderate toxicity, mostly of grade I or II. The bleeding was the most frequent complication. Of the hematological complications, thrombocytopenia was the most common (35 %); neutropenia < 1 × 109/L was observed in 4 patients. GIT complications were identified in 51 (53 %) patients. Atrial fibrillation was registered in 5 patients, who initially had sinus rhythm. The total of 144 infections were diagnosed in 64 (66 %) patients. Severe infections (> grade III) developed in 26 % of patients. The treatment response was assessed in 92 patients. The overall response to treatment was 89 %. Complete remission, partial remission and partial remission with lymphocytosis were achieved in 4 (4 %), 57 (62 %), and 21 (23 %) patients, respectively. The event-free survival and overall survival by the month 10 was 90 % and 91 %, respectively. For this observation period, ECOG status and the number of the lines of therapy prior to ibrutinib had the prognostic value. Conclusion. Ibrutinib was shown to have high efficiency in relapsed/refractory forms of CLL. The nature of the ibrutinib toxicity is fundamentally different from that of the conventional chemotherapy. The frequency of ibrutinib therapy complications and patients’ non-compliance depends on the intensity of the previous treatment of CLL. Despite a short observation period, it can be concluded that ibrutinib had the greatest impact on the patient’s quality of life when administered for the first relapse. The low toxicity of ibrutinib is likely to allow the combination with other antitumor agents.http://bloodjournal.ru/wp-content/uploads/2017/09/1.pdfchronic lymphocytic leukemiadel 17pTP53refractory CLLibrutinibbleedingatrial fibrillation |
| spellingShingle | EA Nikitin EA Dmitrieva MA Panteleev EI Emelina VL Ivanova YuB Kochkareva EG Arshanskaya IE Lazarev EE Markova LA Mukha NG Novitskaya MM Pankrashkina VV Glazunova AV Shubina SA Chernysh NK Khuazheva EV Naumova SA Lugovskaya ME Pochtar’ TN Obukhova OYu Vinogradova GE Gendlin VV Ptushkin Ibrutinib in the Treatment of Refractory Chronic Lymphocytic Leukemia Клиническая онкогематология chronic lymphocytic leukemia del 17p TP53 refractory CLL ibrutinib bleeding atrial fibrillation |
| title | Ibrutinib in the Treatment of Refractory Chronic Lymphocytic Leukemia |
| title_full | Ibrutinib in the Treatment of Refractory Chronic Lymphocytic Leukemia |
| title_fullStr | Ibrutinib in the Treatment of Refractory Chronic Lymphocytic Leukemia |
| title_full_unstemmed | Ibrutinib in the Treatment of Refractory Chronic Lymphocytic Leukemia |
| title_short | Ibrutinib in the Treatment of Refractory Chronic Lymphocytic Leukemia |
| title_sort | ibrutinib in the treatment of refractory chronic lymphocytic leukemia |
| topic | chronic lymphocytic leukemia del 17p TP53 refractory CLL ibrutinib bleeding atrial fibrillation |
| url | http://bloodjournal.ru/wp-content/uploads/2017/09/1.pdf |
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