The average relative dose intensity of R‐CHOP is an independent factor determining favorable overall survival in diffuse large B‐cell lymphoma patients

Abstract The prognosis of diffuse large B‐cell lymphoma (DLBCL) patients depends on lymphoma‐ and patient‐related risk factors and is best estimated by the international prognostic index (IPI). The aim of the study was to determine whether the average relative dose intensity (ARDI) of an anthracycli...

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Main Authors: Monika Długosz‐Danecka, Sebastian Szmit, Tomasz Ogórka, Aleksander B. Skotnicki, Wojciech Jurczak
Format: Article
Language:English
Published: Wiley 2019-03-01
Series:Cancer Medicine
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Online Access:https://doi.org/10.1002/cam4.2008
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author Monika Długosz‐Danecka
Sebastian Szmit
Tomasz Ogórka
Aleksander B. Skotnicki
Wojciech Jurczak
author_facet Monika Długosz‐Danecka
Sebastian Szmit
Tomasz Ogórka
Aleksander B. Skotnicki
Wojciech Jurczak
author_sort Monika Długosz‐Danecka
collection DOAJ
description Abstract The prognosis of diffuse large B‐cell lymphoma (DLBCL) patients depends on lymphoma‐ and patient‐related risk factors and is best estimated by the international prognostic index (IPI). The aim of the study was to determine whether the average relative dose intensity (ARDI) of an anthracycline‐containing regimen could predict DLBCL outcome independently from the IPI. We analyzed 223 white Caucasian DLBCL patients who completed at least four cycles of first‐line immunochemotherapy with rituximab, doxorubicin, cyclophosphamide, vincristine, and prednisone (R‐CHOP). The ARDI was calculated by specially developed software in each individual patient, simultaneously with the chemotherapy prescription, which instantly revealed all causes of its decrease. The relevance of the ARDI for progression‐free/overall survival (PFS/OS) was evaluated. Prolonged intervals between cycles of immunochemotherapy—the most common cause of decreased ARDI (49.3%, 110/223)—were due to neutropenia (absolute neutrophil count <1.0 × 109/L) and infections. Reductions in cytostatic doses were observed in 19.7% (44/223) of patients, mainly as the consequence of cardiotoxicity (23/223, 10.3%). The OS varied significantly when the ARDI was >90% (P < 0.00001). Multivariate analysis confirmed that an ARDI>90% was an IPI‐independent predictor of prolonged PFS (HR = 0.31; 95%CI: 0.20‐0.47; P < 0.00001) and OS (HR = 0.32; 95%CI: 0.21‐0.48; P < 0.00001). With an analytic tool allowing real‐time ARDI assessment, it was possible to maintain an ARDI above 90% in 161 of 223 patients (72%). DLBCL patients with an ARDI >90% have significantly better outcome regardless of the IPI; therefore, our official recommendation is an adequate dose density through efficient neutropenia prophylaxis and cardiac protection.
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spelling doaj-art-c1078c640dda4cdda9855a1b90ecddca2025-01-31T08:47:43ZengWileyCancer Medicine2045-76342019-03-01831103110910.1002/cam4.2008The average relative dose intensity of R‐CHOP is an independent factor determining favorable overall survival in diffuse large B‐cell lymphoma patientsMonika Długosz‐Danecka0Sebastian Szmit1Tomasz Ogórka2Aleksander B. Skotnicki3Wojciech Jurczak4Department of Haematology Jagiellonian University KrakowPolandDepartment of Pulmonary Circulation Thromboembolic Diseases and Cardiology Centre of Postgraduate Medical Education European Health Centre Otwock PolandDepartment of Haematology Jagiellonian University KrakowPolandDepartment of Haematology Jagiellonian University KrakowPolandDepartment of Haematology Jagiellonian University KrakowPolandAbstract The prognosis of diffuse large B‐cell lymphoma (DLBCL) patients depends on lymphoma‐ and patient‐related risk factors and is best estimated by the international prognostic index (IPI). The aim of the study was to determine whether the average relative dose intensity (ARDI) of an anthracycline‐containing regimen could predict DLBCL outcome independently from the IPI. We analyzed 223 white Caucasian DLBCL patients who completed at least four cycles of first‐line immunochemotherapy with rituximab, doxorubicin, cyclophosphamide, vincristine, and prednisone (R‐CHOP). The ARDI was calculated by specially developed software in each individual patient, simultaneously with the chemotherapy prescription, which instantly revealed all causes of its decrease. The relevance of the ARDI for progression‐free/overall survival (PFS/OS) was evaluated. Prolonged intervals between cycles of immunochemotherapy—the most common cause of decreased ARDI (49.3%, 110/223)—were due to neutropenia (absolute neutrophil count <1.0 × 109/L) and infections. Reductions in cytostatic doses were observed in 19.7% (44/223) of patients, mainly as the consequence of cardiotoxicity (23/223, 10.3%). The OS varied significantly when the ARDI was >90% (P < 0.00001). Multivariate analysis confirmed that an ARDI>90% was an IPI‐independent predictor of prolonged PFS (HR = 0.31; 95%CI: 0.20‐0.47; P < 0.00001) and OS (HR = 0.32; 95%CI: 0.21‐0.48; P < 0.00001). With an analytic tool allowing real‐time ARDI assessment, it was possible to maintain an ARDI above 90% in 161 of 223 patients (72%). DLBCL patients with an ARDI >90% have significantly better outcome regardless of the IPI; therefore, our official recommendation is an adequate dose density through efficient neutropenia prophylaxis and cardiac protection.https://doi.org/10.1002/cam4.2008average relative dose intensitycardiotoxicitychemotherapydiffuse large B‐cell lymphomaneutropenia
spellingShingle Monika Długosz‐Danecka
Sebastian Szmit
Tomasz Ogórka
Aleksander B. Skotnicki
Wojciech Jurczak
The average relative dose intensity of R‐CHOP is an independent factor determining favorable overall survival in diffuse large B‐cell lymphoma patients
Cancer Medicine
average relative dose intensity
cardiotoxicity
chemotherapy
diffuse large B‐cell lymphoma
neutropenia
title The average relative dose intensity of R‐CHOP is an independent factor determining favorable overall survival in diffuse large B‐cell lymphoma patients
title_full The average relative dose intensity of R‐CHOP is an independent factor determining favorable overall survival in diffuse large B‐cell lymphoma patients
title_fullStr The average relative dose intensity of R‐CHOP is an independent factor determining favorable overall survival in diffuse large B‐cell lymphoma patients
title_full_unstemmed The average relative dose intensity of R‐CHOP is an independent factor determining favorable overall survival in diffuse large B‐cell lymphoma patients
title_short The average relative dose intensity of R‐CHOP is an independent factor determining favorable overall survival in diffuse large B‐cell lymphoma patients
title_sort average relative dose intensity of r chop is an independent factor determining favorable overall survival in diffuse large b cell lymphoma patients
topic average relative dose intensity
cardiotoxicity
chemotherapy
diffuse large B‐cell lymphoma
neutropenia
url https://doi.org/10.1002/cam4.2008
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