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

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.
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