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Toxicity and Outcomes of Ibrutinib in Chronic Lymphatic Leukemia-Real-World Results from the Study of 215 Patients in Argentina

Received: 30 December 2022     Accepted: 16 February 2023     Published: 17 May 2023
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Abstract

Different pivotal works allowed the approval of ibrutinib as a CLL treatment, both in the first line and in relapsed/refractory patients, the adverse effects differ from conventional chemotherapy, the discontinuation rate was 10%, but in different real-life studies, showed a higher number of complications and medication suspension rates of 40 to 50%. To know the reality of the use of ibrutinib in CLL in our environment, we designed this work with the objectives of evaluating the safety profile of the drug with the description of the adverse effects, their incidence, and their severity. The clinical efficacy will also be studied with the determination of the response achieved, calculation of overall survival (OS) and progression-free survival. Also as an additional objective, the discontinuation rate and its causes will be obtained. A total of 215 patients in 26 centers throughout the country were retrospectively analyzed. 189 patients (88%) had a global response, and the majority 58% achieved a partial response. The 5-year overall survival was 60%, with no difference between patients with different numbers of previous lines. The progression-free survival of the entire group was 5.06 years. 44.7% of the population, presented at least 1 adverse effect. The most frequent ones were: bleeding, thrombocytopenia, pneumonia and diarrhea. Others presented: anemia, neutropenia, infections, AF, HTA, arthralgia, rash, opportunistic infections. Most adverse events were mild to moderate in grade and generally occurred within the first 6 months. The main cause of treatment suspension was the appearance of adverse effects, 37 patients had to suspend it, 27 due to adverse effects (72.97%). In our work, we found that ibrutinib, as a single agent, has outstanding activity in CLL, with a significant percentage of overall responses, even in patients with several lines of prior treatment. Most of the adverse effects were of a mild to moderate degree. The cardiovascular effects of TKI, HBP, and AF, are in percentages similar to those reported in other studies. If we analyze the percentage of treatment discontinuation, which is 17%, mostly due to adverse effects, this finding is similar to pivotal studies. In conclusion, our real-life study confirms the important activity of ibrutinib in patients with CLL, in the first line and relapses, highlighting the low percentage of treatment discontinuation in our environment. We believe our work reflects the real life and daily care of patients with CLL, under treatment with ibrutinib in our environment.

Published in International Journal of Clinical and Experimental Medical Sciences (Volume 9, Issue 3)
DOI 10.11648/j.ijcems.20230903.11
Page(s) 42-48
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2023. Published by Science Publishing Group

Keywords

Ibrutinib, Toxicities, Real Word

References
[1] Winquivst M, Asklid A, Andersson P, Karlsson K, Karlsson C, Lauri B, et al. Real-world results of ibrutinib in patients with relapsed or refractory chronic lymphocytic leukemia: data from 95 consecutive patients treated in a compassionate use program. A study from the Swedish Chronic Lymphocytic Leukemia Group. Haematologica 2016 101 (12); 1573- 1580.
[2] Mato A, Nabhan C, Thompson M, Lamanna N, Brander D, Hill B, et al. Toxicities and outcomes of 616 ibrutinib- treated patients in the United States: a real-world analysis. Haematologica 2018 103 (5) 874-879.
[3] Barr P, Robak T, Owen C, Tedeschi, A, Bairey O, Bartlett N, et al. Sustained efficacy and detailed clinical follow-up of first-line ibrutinib treatment in older patients with chronic lymphocytic leukemia: extended phase 3 results from RESONATE-2. Haematologica 2018 103 (9) 1502-1510.
[4] O’Brien S, Furman R, Coutre S, Flinn I, Burger J, Blum K, et al. Single-agent ibrutinib in treatment-naive and relapsed/refractory chronic lymphocytic leukemia: a 5-year experience. Blood 2018 131 (17) 1910- 1919.
[5] Lipsky A, Farooqui M, Tian X, Martyr S, Cullinane A, Nghiem K, et al. Incidence and risk factors of bleeding-related adverse events in patients with chronic lymphocytic leukemia treated with ibrutinib. Haematologica 2015 100 (12) 1571- 1578.
[6] Coutre S, Byrd J, Hillmen P, Barrientos J, Barr P, Devereux S, et al. Long-term safety of single-agent ibrutinib in patients with chronic lymphocytic leukemia in 3 pivotal studies. Blood advances 2019 3 (12) 1799- 1807.
[7] Woyach J, Ruppert A, Heerema N, Zhao W, Booth A, Ding W, et al. Ibrutinib Regimens versus Chemoinmunotherapy in Older Patients Untreated CLL. N ENGL J MED 2018 1- 12.
[8] Chen L, Bose P, Cruz N, Jiang Y, Wu Q, Thompson P, et al. A pilot study of lower doses of ibrutinib in patients with chronic lymphocytic leukemia. Blood 2018 132 (21) 2249-2259.
[9] Lad D, Malhotra P, Khadwal A, Prakash G, Jain A, Varma S, et al. Reduced Dose Ibrutinib Due to Financial Toxicity in CLL. Indian J Hematol Blood Transfus 2019 35 (2) 260-264.
[10] Hilal T, Banacloche J, Leis J. Chronic lymphocytic leukemia and infection risk in the era of targeted therapies: Linking mechanisms with infections. Blood Reviews 2018 32 387-399.
[11] Rogers K, Mousa L, Zhao Q, Bhat S, Byrd J, Boghdadly Z, et al. Incidence of opportunistic infections during ibrutinib treatment for B-cell malignancies. Leukemia 2019 LETTER.
[12] Williams A, Baran A, Meacham P, Feldman M, Valencia H, Newsom-Stewart C, et al. Analysis of the risk of infection in patients with chronic lymphocytic leukemia in the era of novel therapies. Leukemia & Lymphoma 2017.
[13] Jain P, Keating M, Wierda W, Sivina M, Thompson P, Ferrajoli A, et al. Long-term Follow-up of Treatment with Ibrutinib and Rituximab in Patients with High-Risk Chronic Lymphocytic Leukemia. Clin Cancer Res 2017 23 (9) 2154-2158.
[14] Weerdt I, Koopmans S, Kater A, van Gelder M. Incidence and management of toxicity associated with ibrutinib and idelalisib: a practical approach. Haematologica 2017 102 (10) 1629-1639.
[15] Falchi L, Baron J, Orlikowski C, Ferrajoli A. BCR Signaling Inhibitors: an Overview of Toxicities Associated with Ibrutinib and Idelalisib in Patients with Chronic Lymphocytic Leukemia. Mediterr J Hematol Infect Dis 2016 8 1-12.
[16] Tobinai K, Ogura M, Ishizawa K, Suzuki T, Munakata W, Uchida T, et al. Safety and tolerability of ibrutinib monotherapy in Japanese patients with relapsed/refractory B cell malignancies. Int J Hematol 2016 103 86-94.
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    Horacio Fernández Grecco, Pablo Valdemoros, Maria Jose Mela Osorio, Miguel Pavlovsky, Carolina Pavlovsky, et al. (2023). Toxicity and Outcomes of Ibrutinib in Chronic Lymphatic Leukemia-Real-World Results from the Study of 215 Patients in Argentina. International Journal of Clinical and Experimental Medical Sciences, 9(3), 42-48. https://doi.org/10.11648/j.ijcems.20230903.11

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    ACS Style

    Horacio Fernández Grecco; Pablo Valdemoros; Maria Jose Mela Osorio; Miguel Pavlovsky; Carolina Pavlovsky, et al. Toxicity and Outcomes of Ibrutinib in Chronic Lymphatic Leukemia-Real-World Results from the Study of 215 Patients in Argentina. Int. J. Clin. Exp. Med. Sci. 2023, 9(3), 42-48. doi: 10.11648/j.ijcems.20230903.11

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    AMA Style

    Horacio Fernández Grecco, Pablo Valdemoros, Maria Jose Mela Osorio, Miguel Pavlovsky, Carolina Pavlovsky, et al. Toxicity and Outcomes of Ibrutinib in Chronic Lymphatic Leukemia-Real-World Results from the Study of 215 Patients in Argentina. Int J Clin Exp Med Sci. 2023;9(3):42-48. doi: 10.11648/j.ijcems.20230903.11

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  • @article{10.11648/j.ijcems.20230903.11,
      author = {Horacio Fernández Grecco and Pablo Valdemoros and Maria Jose Mela Osorio and Miguel Pavlovsky and Carolina Pavlovsky and Astrid Pavlovsky and Juan Dupont and Dardo Riveros and Juan Altuve and Gonzalo Ferini and Victoria Otero and Fernando Warley and Fernando Bezares and Alicia Enrico and Laura Kornblihtt and Silvana Cugliari and Augusto Miroli and Manuel Bonder and Alicia Bistman and Julio Pose and Marta Zerga and Maria Cabrejo and Jorge Jerez and Maria Cardenas and Patricio Pereyra and Juan Maradei and Ana Portalez and Fernanda Tosin and Virginia Gilli and Rodrigo Vallejo and Noelia Masachessi and Eriberto Roveri and Susana Mari and Magali Colucci and Basilio Pertiné and Noemi Pintos},
      title = {Toxicity and Outcomes of Ibrutinib in Chronic Lymphatic Leukemia-Real-World Results from the Study of 215 Patients in Argentina},
      journal = {International Journal of Clinical and Experimental Medical Sciences},
      volume = {9},
      number = {3},
      pages = {42-48},
      doi = {10.11648/j.ijcems.20230903.11},
      url = {https://doi.org/10.11648/j.ijcems.20230903.11},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijcems.20230903.11},
      abstract = {Different pivotal works allowed the approval of ibrutinib as a CLL treatment, both in the first line and in relapsed/refractory patients, the adverse effects differ from conventional chemotherapy, the discontinuation rate was 10%, but in different real-life studies, showed a higher number of complications and medication suspension rates of 40 to 50%. To know the reality of the use of ibrutinib in CLL in our environment, we designed this work with the objectives of evaluating the safety profile of the drug with the description of the adverse effects, their incidence, and their severity. The clinical efficacy will also be studied with the determination of the response achieved, calculation of overall survival (OS) and progression-free survival. Also as an additional objective, the discontinuation rate and its causes will be obtained. A total of 215 patients in 26 centers throughout the country were retrospectively analyzed. 189 patients (88%) had a global response, and the majority 58% achieved a partial response. The 5-year overall survival was 60%, with no difference between patients with different numbers of previous lines. The progression-free survival of the entire group was 5.06 years. 44.7% of the population, presented at least 1 adverse effect. The most frequent ones were: bleeding, thrombocytopenia, pneumonia and diarrhea. Others presented: anemia, neutropenia, infections, AF, HTA, arthralgia, rash, opportunistic infections. Most adverse events were mild to moderate in grade and generally occurred within the first 6 months. The main cause of treatment suspension was the appearance of adverse effects, 37 patients had to suspend it, 27 due to adverse effects (72.97%). In our work, we found that ibrutinib, as a single agent, has outstanding activity in CLL, with a significant percentage of overall responses, even in patients with several lines of prior treatment. Most of the adverse effects were of a mild to moderate degree. The cardiovascular effects of TKI, HBP, and AF, are in percentages similar to those reported in other studies. If we analyze the percentage of treatment discontinuation, which is 17%, mostly due to adverse effects, this finding is similar to pivotal studies. In conclusion, our real-life study confirms the important activity of ibrutinib in patients with CLL, in the first line and relapses, highlighting the low percentage of treatment discontinuation in our environment. We believe our work reflects the real life and daily care of patients with CLL, under treatment with ibrutinib in our environment.},
     year = {2023}
    }
    

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  • TY  - JOUR
    T1  - Toxicity and Outcomes of Ibrutinib in Chronic Lymphatic Leukemia-Real-World Results from the Study of 215 Patients in Argentina
    AU  - Horacio Fernández Grecco
    AU  - Pablo Valdemoros
    AU  - Maria Jose Mela Osorio
    AU  - Miguel Pavlovsky
    AU  - Carolina Pavlovsky
    AU  - Astrid Pavlovsky
    AU  - Juan Dupont
    AU  - Dardo Riveros
    AU  - Juan Altuve
    AU  - Gonzalo Ferini
    AU  - Victoria Otero
    AU  - Fernando Warley
    AU  - Fernando Bezares
    AU  - Alicia Enrico
    AU  - Laura Kornblihtt
    AU  - Silvana Cugliari
    AU  - Augusto Miroli
    AU  - Manuel Bonder
    AU  - Alicia Bistman
    AU  - Julio Pose
    AU  - Marta Zerga
    AU  - Maria Cabrejo
    AU  - Jorge Jerez
    AU  - Maria Cardenas
    AU  - Patricio Pereyra
    AU  - Juan Maradei
    AU  - Ana Portalez
    AU  - Fernanda Tosin
    AU  - Virginia Gilli
    AU  - Rodrigo Vallejo
    AU  - Noelia Masachessi
    AU  - Eriberto Roveri
    AU  - Susana Mari
    AU  - Magali Colucci
    AU  - Basilio Pertiné
    AU  - Noemi Pintos
    Y1  - 2023/05/17
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    DO  - 10.11648/j.ijcems.20230903.11
    T2  - International Journal of Clinical and Experimental Medical Sciences
    JF  - International Journal of Clinical and Experimental Medical Sciences
    JO  - International Journal of Clinical and Experimental Medical Sciences
    SP  - 42
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    PB  - Science Publishing Group
    SN  - 2469-8032
    UR  - https://doi.org/10.11648/j.ijcems.20230903.11
    AB  - Different pivotal works allowed the approval of ibrutinib as a CLL treatment, both in the first line and in relapsed/refractory patients, the adverse effects differ from conventional chemotherapy, the discontinuation rate was 10%, but in different real-life studies, showed a higher number of complications and medication suspension rates of 40 to 50%. To know the reality of the use of ibrutinib in CLL in our environment, we designed this work with the objectives of evaluating the safety profile of the drug with the description of the adverse effects, their incidence, and their severity. The clinical efficacy will also be studied with the determination of the response achieved, calculation of overall survival (OS) and progression-free survival. Also as an additional objective, the discontinuation rate and its causes will be obtained. A total of 215 patients in 26 centers throughout the country were retrospectively analyzed. 189 patients (88%) had a global response, and the majority 58% achieved a partial response. The 5-year overall survival was 60%, with no difference between patients with different numbers of previous lines. The progression-free survival of the entire group was 5.06 years. 44.7% of the population, presented at least 1 adverse effect. The most frequent ones were: bleeding, thrombocytopenia, pneumonia and diarrhea. Others presented: anemia, neutropenia, infections, AF, HTA, arthralgia, rash, opportunistic infections. Most adverse events were mild to moderate in grade and generally occurred within the first 6 months. The main cause of treatment suspension was the appearance of adverse effects, 37 patients had to suspend it, 27 due to adverse effects (72.97%). In our work, we found that ibrutinib, as a single agent, has outstanding activity in CLL, with a significant percentage of overall responses, even in patients with several lines of prior treatment. Most of the adverse effects were of a mild to moderate degree. The cardiovascular effects of TKI, HBP, and AF, are in percentages similar to those reported in other studies. If we analyze the percentage of treatment discontinuation, which is 17%, mostly due to adverse effects, this finding is similar to pivotal studies. In conclusion, our real-life study confirms the important activity of ibrutinib in patients with CLL, in the first line and relapses, highlighting the low percentage of treatment discontinuation in our environment. We believe our work reflects the real life and daily care of patients with CLL, under treatment with ibrutinib in our environment.
    VL  - 9
    IS  - 3
    ER  - 

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Author Information
  • Department of Hematology, Sanatorio Julio Mendez, Buenos Aires, Argentina

  • Department of Hematology, Sanatorio Julio Mendez, Buenos Aires, Argentina

  • Department of Hematology, Fundaleu, Buenos Aires, Argentina

  • Department of Hematology, Fundaleu, Buenos Aires, Argentina

  • Department of Hematology, Fundaleu, Buenos Aires, Argentina

  • Department of Hematology, Fundaleu, Buenos Aires, Argentina

  • Department of Hematology, Centro de Educacion Medica e Investigacion Clinica, Buenos Aires, Argentina

  • Department of Hematology, Centro de Educacion Medica e Investigacion Clinica, Buenos Aires, Argentina

  • Department of Hematology, Centro de Educacion Medica e Investigacion Clinica, Buenos Aires, Argentina

  • Department of Hematology, Hospital Italiano, Buenos Aires, Argentina

  • Department of Hematology, Hospital Italiano, Buenos Aires, Argentina

  • Department of Hematology, Hospital Italiano, Buenos Aires, Argentina

  • Department of Hematology, Hospital Alvarez, Buenos Aires, Argentina

  • Department of Hematology, Hospital Italiano La Plata, Buenos Aires, Argentina

  • Department of Hematology, Hospital de Clinicas Jose de San Martin Universidad de Buenos Aires, Buenos Aires, Argentina

  • Department of Hematology, Instituto Roffo Universidad de Buenos Aires, Argentina

  • Department of Hematology, Hospital Churruca, Buenos Aires, Argentina

  • Department of Hematology, Sanatorio Trinidad Mitre, Buenos Aires, Argentina

  • Department of Hematology, Hospital Ramos Mejia, Buenos Aires, Argentina

  • Department of Hematology, Sanatorio Otamendi, Buenos Aires, Argentina

  • Department of Hematology, Hospital Aleman, Buenos Aires, Argentina

  • Department of Hematology, Sanatorio Julio Mendez, Buenos Aires, Argentina

  • Department of Hematology, Sanatorio Julio Mendez, Buenos Aires, Argentina

  • Department of Hematology, Hospital Italiano San Justo, Buenos Aires, Argentina

  • Department of Hematology, Hospital Posadas, Buenos Aires, Argentina

  • Department of Hematology, Hospital Emilio Ferreyra, Bahia Blanca, Argentina

  • Department of Hematology, Hospital Centeno, La Pampa, Argentina

  • Department of Hematology, Hospital El Cruce, Buenos Aires, Argentina

  • Department of Hematology, Hospital Entre Rios, Entre Rios, Argentina

  • Department of Hematology, Hospital Bernardo Houssay, Buenos Aires, Argentina

  • Department of Hematology, Centro Oncologico San Luis, San Luis, Argentina

  • Department of Hematology, Sanatorio Norte Rosario, Santa Fe, Argentina

  • Department of Hematology, Hospital Blas Dubary, Buenos Aires, Argentina

  • Department of Hematology, Instituto Conciencia, Neuquen, Argentina

  • Department of Hematology, Instituto Medico de Alta Complejidad, Salta, Argentina

  • Department of Hematology, Sanatorio Julio Mendez, Buenos Aires, Argentina

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