Targeted therapies in CLL/SLL and the cumulative incidence of infection: A systematic review and meta-analysis
Background: Patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) are prone to infections.Aims: Provide a pooled estimate of the cumulative incidence for infections that fulfilled the criteria associated with severe infectious adverse events for grade 3 or higher (includi...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.989830/full |
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| author | Stephanos Vassilopoulos Stephanos Vassilopoulos Fadi Shehadeh Fadi Shehadeh Fadi Shehadeh Markos Kalligeros Markos Kalligeros Quynh-Lam Tran Quynh-Lam Tran Fred Schiffman Fred Schiffman Eleftherios Mylonakis Eleftherios Mylonakis |
| author_facet | Stephanos Vassilopoulos Stephanos Vassilopoulos Fadi Shehadeh Fadi Shehadeh Fadi Shehadeh Markos Kalligeros Markos Kalligeros Quynh-Lam Tran Quynh-Lam Tran Fred Schiffman Fred Schiffman Eleftherios Mylonakis Eleftherios Mylonakis |
| author_sort | Stephanos Vassilopoulos |
| collection | DOAJ |
| description | Background: Patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) are prone to infections.Aims: Provide a pooled estimate of the cumulative incidence for infections that fulfilled the criteria associated with severe infectious adverse events for grade 3 or higher (including pneumonia, febrile neutropenia and sepsis) in patients who receive targeted therapies.Methods: We searched PubMed and EMBASE for randomized controlled trials (RCT) that included patients with CLL/SLL who received targeted therapies and performed a random-effects meta-analysis to estimate the cumulative incidence of infections.Results: Of 2,914 studies screened, we retrieved 31 which evaluated 11,660 patients. The pooled cumulative incidence of infections for patients who received treatment regimens based on a BTK inhibitors was 19.86%. For patients who received treatment based on rituximab and second generation anti-CD20 monoclonal antibodies, the pooled cumulative incidence of infections was 19.85 and 13.46%, respectively. Regarding PI3K inhibitor-based regimens the cumulative incidence of severe infections was 30.89%. BCL-2 inhibitors had a cumulative incidence of infections of 17.49% while lenalidomide and alemtuzumab had an incidence of 13.33 and 45.09%, respectively. The cumulative incidence of pneumonia ranged from 3.01 to 8.45% while febrile neutropenia ranged from 2.68 to 10.80%. Regarding sepsis, the cumulative incidence ranged from 0.9 to 4.48%.Conclusion: Patients with CLL/SLL who receive targeted therapies may develop severe infections at significant rates that, in addition to disease stage and other complications, depend on the mechanism of action of the used drug. Surveillance for infections and development of effective prophylactic strategies are critical for patients with CLL/SLL who receive targeted therapies.Systematic Review Registration: [https://systematicreview.gov/], identifier [registration number] |
| first_indexed | 2024-04-11T21:05:29Z |
| format | Article |
| id | doaj.art-01e0f042be60441d94d55e9d53a9e874 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-11T21:05:29Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-01e0f042be60441d94d55e9d53a9e8742022-12-22T04:03:21ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-09-011310.3389/fphar.2022.989830989830Targeted therapies in CLL/SLL and the cumulative incidence of infection: A systematic review and meta-analysisStephanos Vassilopoulos0Stephanos Vassilopoulos1Fadi Shehadeh2Fadi Shehadeh3Fadi Shehadeh4Markos Kalligeros5Markos Kalligeros6Quynh-Lam Tran7Quynh-Lam Tran8Fred Schiffman9Fred Schiffman10Eleftherios Mylonakis11Eleftherios Mylonakis12Infectious Diseases Division, Rhode Island Hospital, Providence, RI, United StatesWarren Alpert Medical School of Brown University, Providence, RI, United StatesInfectious Diseases Division, Rhode Island Hospital, Providence, RI, United StatesWarren Alpert Medical School of Brown University, Providence, RI, United StatesSchool of Electrical and Computer Engineering, National Technical University of Athens, Athens, GreeceInfectious Diseases Division, Rhode Island Hospital, Providence, RI, United StatesWarren Alpert Medical School of Brown University, Providence, RI, United StatesInfectious Diseases Division, Rhode Island Hospital, Providence, RI, United StatesWarren Alpert Medical School of Brown University, Providence, RI, United StatesWarren Alpert Medical School of Brown University, Providence, RI, United StatesDivision of Hematology-Oncology, Rhode Island Hospital and The Miriam Hospital, Providence, RI, United StatesInfectious Diseases Division, Rhode Island Hospital, Providence, RI, United StatesWarren Alpert Medical School of Brown University, Providence, RI, United StatesBackground: Patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) are prone to infections.Aims: Provide a pooled estimate of the cumulative incidence for infections that fulfilled the criteria associated with severe infectious adverse events for grade 3 or higher (including pneumonia, febrile neutropenia and sepsis) in patients who receive targeted therapies.Methods: We searched PubMed and EMBASE for randomized controlled trials (RCT) that included patients with CLL/SLL who received targeted therapies and performed a random-effects meta-analysis to estimate the cumulative incidence of infections.Results: Of 2,914 studies screened, we retrieved 31 which evaluated 11,660 patients. The pooled cumulative incidence of infections for patients who received treatment regimens based on a BTK inhibitors was 19.86%. For patients who received treatment based on rituximab and second generation anti-CD20 monoclonal antibodies, the pooled cumulative incidence of infections was 19.85 and 13.46%, respectively. Regarding PI3K inhibitor-based regimens the cumulative incidence of severe infections was 30.89%. BCL-2 inhibitors had a cumulative incidence of infections of 17.49% while lenalidomide and alemtuzumab had an incidence of 13.33 and 45.09%, respectively. The cumulative incidence of pneumonia ranged from 3.01 to 8.45% while febrile neutropenia ranged from 2.68 to 10.80%. Regarding sepsis, the cumulative incidence ranged from 0.9 to 4.48%.Conclusion: Patients with CLL/SLL who receive targeted therapies may develop severe infections at significant rates that, in addition to disease stage and other complications, depend on the mechanism of action of the used drug. Surveillance for infections and development of effective prophylactic strategies are critical for patients with CLL/SLL who receive targeted therapies.Systematic Review Registration: [https://systematicreview.gov/], identifier [registration number]https://www.frontiersin.org/articles/10.3389/fphar.2022.989830/fullchronic lymphocytic leukemia (CLL)infectionstargeted therapiesibrutinibidelalisibmonoclonal antibodies |
| spellingShingle | Stephanos Vassilopoulos Stephanos Vassilopoulos Fadi Shehadeh Fadi Shehadeh Fadi Shehadeh Markos Kalligeros Markos Kalligeros Quynh-Lam Tran Quynh-Lam Tran Fred Schiffman Fred Schiffman Eleftherios Mylonakis Eleftherios Mylonakis Targeted therapies in CLL/SLL and the cumulative incidence of infection: A systematic review and meta-analysis Frontiers in Pharmacology chronic lymphocytic leukemia (CLL) infections targeted therapies ibrutinib idelalisib monoclonal antibodies |
| title | Targeted therapies in CLL/SLL and the cumulative incidence of infection: A systematic review and meta-analysis |
| title_full | Targeted therapies in CLL/SLL and the cumulative incidence of infection: A systematic review and meta-analysis |
| title_fullStr | Targeted therapies in CLL/SLL and the cumulative incidence of infection: A systematic review and meta-analysis |
| title_full_unstemmed | Targeted therapies in CLL/SLL and the cumulative incidence of infection: A systematic review and meta-analysis |
| title_short | Targeted therapies in CLL/SLL and the cumulative incidence of infection: A systematic review and meta-analysis |
| title_sort | targeted therapies in cll sll and the cumulative incidence of infection a systematic review and meta analysis |
| topic | chronic lymphocytic leukemia (CLL) infections targeted therapies ibrutinib idelalisib monoclonal antibodies |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.989830/full |
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