Title :

Rituximab exposure is influenced by baseline metabolic tumor volume and predicts outcome of DLBCL patients: a Lymphoma Study Association report

Author(s) :

Tout, Mira [Auteur]
Casasnovas, Olivier [Auteur]
Meignan, Michel [Auteur]
Lamy, Thierry [Auteur]
Morschhauser, Franck [Auteur]
Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 [GRITA]
Salles, Gilles [Auteur]
Gyan, Emmanuel [Auteur]
Haioun, Corinne [Auteur]
Mercier, Melanie [Auteur]
Feugier, Pierre [Auteur]
Boussetta, Sami [Auteur]
Paintaud, Gilles [Auteur]
Ternant, David [Auteur]
Cartron, Guillaume [Auteur]

Journal title :

Blood

Abbreviated title :

Blood

Volume number :

129

Pages :

2616-2623

Publication date :

2017

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

High variability in patient outcome after rituximab-based treatment is partly explained by rituximab concentrations, and pharmacokinetic (PK) variability could be influenced by tumor burden. We aimed at quantifying the ...
Show more >High variability in patient outcome after rituximab-based treatment is partly explained by rituximab concentrations, and pharmacokinetic (PK) variability could be influenced by tumor burden. We aimed at quantifying the influence of baseline total metabolic tumor volume (TMTV0) on rituximab PK and of TMTV0 and rituximab exposure on outcome in patients with diffuse large B-cell lymphoma (DLBCL). TMTV0 was measured by 18F-fluorodeoxyglucose-positron emission tomography-computed tomography in 108 previously untreated DLBCL patients who received four 375 mg/m2 rituximab infusions every 2 weeks in combination with chemotherapy in 2 prospective trials. A 2-compartment population model allowed describing rituximab PK and calculating rituximab exposure (area under the concentration-time curve; AUC). The association of TMTV0 and AUC with metabolic response after 4 cycles, as well as progression-free survival (PFS) and overall survival (OS), was assessed using logistic regression and Cox models, respectively. Cutoff values for patient outcome were determined using receiver operating characteristic curve analysis. Exposure to rituximab decreased as TMTV0 increased (R2 = 0.41, P < .0001). A high AUC in cycle 1 (≥9400 mg × h per liter) was associated with better response (odds ratio, 5.56; P = .0006) and longer PFS (hazard ratio [HR], 0.38; P = .011) and OS (HR, 0.17; P = .001). A nomogram for rituximab dose needed to obtain optimal AUC according to TMTV0 was constructed, and the 375 mg/m2 classical dose would be suitable for patients with TMTV0 <281 cm3 In summary, rituximab exposure is influenced by TMTV0 and correlates with response and outcome of DLBCL patients. Dose individualization according to TMTV0 should be evaluated in prospective studies. These studies were registered at www.clinicaltrials.gov as #NCT00498043 and #NCT00841945.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
CHU Lille

Collections :

• Groupe de Recherche sur les formes Injectables et les Technologies Associées (GRITA) - ULR 7365

Research team(s) :

Innovation/évaluation des médicaments injectables

Submission date :

2019-02-26T17:07:14Z