Baseline lymphopenia should not be used as exclusion criteria in early clinical trials investigating immune checkpoint blockers (PD-1/PD-L1 inhibitors). (October 2017)

• Record Type: Journal Article
• Authors: Sun, Roger; Champiat, Stéphane; Dercle, Laurent; Aspeslagh, Sandrine; Castanon, Eduardo; Limkin, Elaine Johanna; Baldini, Capucine; Postel-Vinay, Sophie; Hollebecque, Antoine; Massard, Christophe; Ammari, Samy; Deutsch, Eric; Soria, Jean-Charles; Marabelle, Aurélien; Ferté, Charles
• Is Part Of: European journal of cancer. Volume 84(2017)
• Page Start: 202
• Page End: 211
• Publication Date: 2017-10
• Subjects: Phase 1 trial -- Immunotherapy -- Lymphopenia -- Eligibility criteria; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Cancer; Tumors; Electronic journals; Periodicals; Electronic journals; 616.994
• DOI: 10.1016/j.ejca.2017.07.033
• Languages: English
• ISSNs: 0959-8049

Abstract

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. Highlights: A number of phase I immunotherapy trials exclude patients with low lymphocyte counts. Lymphopenia <1 G/l was not associated with poor outcome in phase I cancer patients. Lymphopenia should not be an exclusion criteria for anti-PD1/PD-L1 phase I trials.