Roger Sun1, Stéphane Champiat2, Laurent Dercle3, Sandrine Aspeslagh2, Eduardo Castanon2, Elaine Johanna Limkin4, Capucine Baldini2, Sophie Postel-Vinay2, Antoine Hollebecque2, Christophe Massard2, Samy Ammari5, Eric Deutsch6, Jean-Charles Soria7, Aurélien Marabelle2, Charles Ferté8. 1. Drug Development Department, Gustave Roussy Cancer Campus, 94800 Villejuif, France; Department of Radiation Oncology, Gustave Roussy Cancer Campus, 94800 Villejuif, France. 2. Drug Development Department, Gustave Roussy Cancer Campus, 94800 Villejuif, France. 3. Department of Nuclear Medicine and Endocrine Oncology, Gustave Roussy Cancer Campus, 94800 Villejuif, France. 4. Department of Radiation Oncology, Gustave Roussy Cancer Campus, 94800 Villejuif, France. 5. Department of Radiology, Gustave Roussy Cancer Campus, 94800 Villejuif, France. 6. Drug Development Department, Gustave Roussy Cancer Campus, 94800 Villejuif, France; Department of Radiation Oncology, Gustave Roussy Cancer Campus, 94800 Villejuif, France; Paris-Sud University, 94270 Le Kremlin-Bicêtre, France. 7. Drug Development Department, Gustave Roussy Cancer Campus, 94800 Villejuif, France; Paris-Sud University, 94270 Le Kremlin-Bicêtre, France. 8. Drug Development Department, Gustave Roussy Cancer Campus, 94800 Villejuif, France; Department of Head and Neck Oncology, Gustave Roussy Cancer Campus, 94800 Villejuif, France. Electronic address: charles.ferte@gustaveroussy.fr.
Abstract
INTRODUCTION: A number of phase I immunotherapy trials for cancer patients incorporate the absolute lymphocyte count (ALC) as an inclusion criteria. This study aims to assess whether ALC is associated with a lack of response to anti-PD-1/PD-L1 in early clinical trials. METHODS: All consecutive patients treated with anti-PD-1/PD-L1 monotherapy in phase I trials in our institution between December 2011 and January 2014 were reviewed. Baseline ALC, neutrophil-to-lymphocyte ratio (NLR), Royal-Marsden Hospital (RMH) prognostic score, objective response rate (ORR) and disease control rate (DCR = SD + PR + CR, stable disease (SD), partial response (PR), complete response (CR)) defined by Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1 were retrieved. RESULTS: Out of a total of 167 patients, 48 (28.7%) and 8 patients (4.8%) had baseline ALCs of <1 G/l and <0.5 G/l, respectively. The RECIST change (%) was not correlated with ALC (G/l) (Spearman's rho = -0.06, P = 0.43). We did not observe any difference in terms of ORR (8.3% versus 15.1%, P = 0.32) or of DCR (58.3% versus 61.3%, P = 0.73) between patients with ALC <1 G/l versus >1 G/l. When using 0.5 G/l as ALC threshold, we did not find any difference either in ORR or in DCR. In a multivariate Cox regression analysis, baseline ALC was not associated with overall survival, whereas the RMH and the number of previous lines of treatment remained independent prognostic factors. CONCLUSIONS: Baseline ALC was not associated with response to anti-PD-1/PD-L1 in cancer patients enrolled in phase I trials. Patients should not be excluded from early phase clinical trials testing immune checkpoints blockers because of ALC.
INTRODUCTION: A number of phase I immunotherapy trials for cancerpatients incorporate the absolute lymphocyte count (ALC) as an inclusion criteria. This study aims to assess whether ALC is associated with a lack of response to anti-PD-1/PD-L1 in early clinical trials. METHODS: All consecutive patients treated with anti-PD-1/PD-L1 monotherapy in phase I trials in our institution between December 2011 and January 2014 were reviewed. Baseline ALC, neutrophil-to-lymphocyte ratio (NLR), Royal-Marsden Hospital (RMH) prognostic score, objective response rate (ORR) and disease control rate (DCR = SD + PR + CR, stable disease (SD), partial response (PR), complete response (CR)) defined by Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1 were retrieved. RESULTS: Out of a total of 167 patients, 48 (28.7%) and 8 patients (4.8%) had baseline ALCs of <1 G/l and <0.5 G/l, respectively. The RECIST change (%) was not correlated with ALC (G/l) (Spearman's rho = -0.06, P = 0.43). We did not observe any difference in terms of ORR (8.3% versus 15.1%, P = 0.32) or of DCR (58.3% versus 61.3%, P = 0.73) between patients with ALC <1 G/l versus >1 G/l. When using 0.5 G/l as ALC threshold, we did not find any difference either in ORR or in DCR. In a multivariate Cox regression analysis, baseline ALC was not associated with overall survival, whereas the RMH and the number of previous lines of treatment remained independent prognostic factors. CONCLUSIONS: Baseline ALC was not associated with response to anti-PD-1/PD-L1 in cancerpatients enrolled in phase I trials. Patients should not be excluded from early phase clinical trials testing immune checkpoints blockers because of ALC.
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