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THE AVERAGE RELATIVE DOSE INTENSITY OF R-CHOP IS AN INDEPENDENT PROGNOSTIC FACTOR DETERMINING OVERALL SURVIVAL IN DIFFUSE LARGE B CELL LYMPHOMA PATIENTS.
Author(s): ,
Monika Długosz-Danecka
Affiliations:
Department of Hematology,Jagiellonian University,Krakow,Poland
,
Sebastian Szmit
Affiliations:
Department of Pulmonary Circulation, Thromboembolic Diseases and Cardiology,Centre of Postgraduate Medical Education, European Health Centre,Otwock,Poland
,
Tomasz Ogórka
Affiliations:
Department of Hematology,Jagiellonian University,Krakow,Poland
,
Katarzyna Krawczyk
Affiliations:
Department of Hematology,Jagiellonian University,Krakow,Poland
,
Ewa Łątka
Affiliations:
Department of Hematology,Jagiellonian University,Krakow,Poland
,
Aleksander Skotnicki
Affiliations:
Department of Hematology,Jagiellonian University,Krakow,Poland
Wojciech Jurczak
Affiliations:
Department of Hematology,Jagiellonian University,Krakow,Poland
(Abstract release date: 05/17/18) EHA Library. Dlugosz-Danecka M. 06/14/18; 216126; PB1751
Monika Dlugosz-Danecka
Monika Dlugosz-Danecka
Contributions
Abstract

Abstract: PB1751

Type: Publication Only

Background
Prognosis of diffuse large B cell lymphoma (DLBCL) patients depends on lymphoma and patient-related risk factors, best summarized in IPI (International Prognostic Index). The aim of the study was to determine whether the average relative dose intensity (ARDI) of anthracycline containing regimen could be an IPI-independent prognostic factor.T

Aims
The aim of the analysis was to assess the relationship between the calculated ARDI and PFS and OS in DLBCL patients treated with R-CHOP chemotherapy.

Methods

We analysed 223 white Caucasian DLBCL patients, who completed at least four cycles of first-line R-CHOP immunochemotherapy (Rituximab, Doxorubicin, Cyclophosphamide, Vincristine, Prednisone). ARDI was calculated by specially developed software, in each individual patient, simultaneously with chemotherapy prescription. It allowed to address instantly all revealed causes of decreased ARDI. Importance of ARDI for progression-free/overall survival (PFS/OS) was evaluated. 

Results

ARDI was decreased due to prolonged interval between immunochemotherapy cycles caused by neutropenia and infections (absolute neutrophil count <1,0 x 109/l) in 49.32% (110/223) or reduction of cytostatic doses in 19.73% (44/223) patients mainly as the consequence of cardiotoxicity or neutropenia (85,18% and 14,81% respectively, estimating in the group of patients with reduced doses of cytostatics). Progression free and overall survival (PFS and OS) varied significantly for ARDI >90%, 89-80% and <80% respectively (p<0.00001). Multivariate analysis confirmed that ARDI>90% was an IPI independent predictor of prolonged PFS (Hazard Ratio (HR), Confidence Interval (CI): HR=0.31; 95%CI: 0.20-0.47; p<0.000001) and OS (HR=0.32; 95%CI: 0.21-0.48; p<0.000001). Even with real time ARDI analysis it was possible to maintain it above 90% in 161 of 223 patients (72%).  Further improvement may be possible only after implementing primary neutropenia prophylaxis and primary cardioprotection. 

Table 1. Favorable PFS and OS depending on high ARDI and low IPI (Cox proportional risk model).

Survival

ARDI >90%

low IPI (0 or 1)

multivariate

analysis

PFS

HR=0.31

95%CI: 0.20 - 0.47

p<0.000001

HR=0.43

95%CI: 0.24 - 0.76

p=0.004

OS

HR=0.32

95%CI: 0.21 - 0.48

p<0.000001

HR=0.48

95%CI: 0.27 - 0.85

p=0.01

Conclusion
DLBCL patients with ARDI >90% have significantly better outcome regardless of IPI, therefore we postulate to regard adequate dose density as an official recommendation.

Session topic: 21. Aggressive Non-Hodgkin lymphoma - Clinical

Keyword(s): chemotherapy, Diffuse large B cell lymphoma, Dose intensity, neutropenia

Abstract: PB1751

Type: Publication Only

Background
Prognosis of diffuse large B cell lymphoma (DLBCL) patients depends on lymphoma and patient-related risk factors, best summarized in IPI (International Prognostic Index). The aim of the study was to determine whether the average relative dose intensity (ARDI) of anthracycline containing regimen could be an IPI-independent prognostic factor.T

Aims
The aim of the analysis was to assess the relationship between the calculated ARDI and PFS and OS in DLBCL patients treated with R-CHOP chemotherapy.

Methods

We analysed 223 white Caucasian DLBCL patients, who completed at least four cycles of first-line R-CHOP immunochemotherapy (Rituximab, Doxorubicin, Cyclophosphamide, Vincristine, Prednisone). ARDI was calculated by specially developed software, in each individual patient, simultaneously with chemotherapy prescription. It allowed to address instantly all revealed causes of decreased ARDI. Importance of ARDI for progression-free/overall survival (PFS/OS) was evaluated. 

Results

ARDI was decreased due to prolonged interval between immunochemotherapy cycles caused by neutropenia and infections (absolute neutrophil count <1,0 x 109/l) in 49.32% (110/223) or reduction of cytostatic doses in 19.73% (44/223) patients mainly as the consequence of cardiotoxicity or neutropenia (85,18% and 14,81% respectively, estimating in the group of patients with reduced doses of cytostatics). Progression free and overall survival (PFS and OS) varied significantly for ARDI >90%, 89-80% and <80% respectively (p<0.00001). Multivariate analysis confirmed that ARDI>90% was an IPI independent predictor of prolonged PFS (Hazard Ratio (HR), Confidence Interval (CI): HR=0.31; 95%CI: 0.20-0.47; p<0.000001) and OS (HR=0.32; 95%CI: 0.21-0.48; p<0.000001). Even with real time ARDI analysis it was possible to maintain it above 90% in 161 of 223 patients (72%).  Further improvement may be possible only after implementing primary neutropenia prophylaxis and primary cardioprotection. 

Table 1. Favorable PFS and OS depending on high ARDI and low IPI (Cox proportional risk model).

Survival

ARDI >90%

low IPI (0 or 1)

multivariate

analysis

PFS

HR=0.31

95%CI: 0.20 - 0.47

p<0.000001

HR=0.43

95%CI: 0.24 - 0.76

p=0.004

OS

HR=0.32

95%CI: 0.21 - 0.48

p<0.000001

HR=0.48

95%CI: 0.27 - 0.85

p=0.01

Conclusion
DLBCL patients with ARDI >90% have significantly better outcome regardless of IPI, therefore we postulate to regard adequate dose density as an official recommendation.

Session topic: 21. Aggressive Non-Hodgkin lymphoma - Clinical

Keyword(s): chemotherapy, Diffuse large B cell lymphoma, Dose intensity, neutropenia

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