For most patients with mantle cell lymphoma (MCL), programmed death 1 and its ligand (PD-1/PD-L1) inhibitors do not appear to be appropriate treatment options, according to Farid Kosari.

In patients with MCL, the expression of PD-L1 as a predictive marker and prognostic has not been fully evaluated, the study authors wrote. To address this knowledge gap, Kosari and colleagues conducted a retrospective study, published in BMC Cancer, to examine PD-1/PD-L1 expression in MCL specimens and implications for the use of immune checkpoint inhibitors.

In 79 mostly male patients with MCL (mean age, 60.08±10.78), researchers examined formalin-fixed paraffin-embedded blocks based on patient immunohistochemistry (IHC), using the IHC method to stain patient samples for PD-1 and PD-L1. Positive PD-1/PD-L1 expression was defined as moderate to strong or membranous or membranous/cytoplasmic in at least 5% of tumors and/or 20% of associated immune cells. The nuclear protein Ki67 and variant was utilized to assess tumor aggressiveness.

One-Quarter of Patients Had Aggressive Tumors

In the total cohort, Kosari and colleagues observed that the incidence of aggressive tumors was 25%. In 15.0% and 3.8% of tumor cells, positive PD-1 and PD-L1 expressions, respectively, were identified. In 0% and 8.9% of background cells, PD-1 and PD-L1, respectively, were positive. No meaningful differences were seen in terms of study parameters between positive and negative groups for both PD-1 and PD-L1 proteins.

PD-1 tumor cell percentage was negatively associated with age (r = -0.254; P =0.046). The study team noted that the negative effect of age on the efficacy of checkpoint inhibitor therapy may also explain the heightened cancer risk with age due to immune senescence, which should be examined in future research.

“… The percentage of PD1-positive tumor cells in [patients with] MCL decreased with age,” the study authors wrote. They noted that these findings are relevant for determining which patients may benefit from PD-1 inhibitors, because a patient’s age may negatively impact the treatment efficacy.

“[Our findings] indicated a relatively low immunohistochemical expression for PD-1 and PD-L1 markers in tumoral and background cells in patients with [MCL],” the study authors wrote. “Therefore, PD-1 or PD-L1 inhibitors do not seem to be suitable treatment options for immunotherapy in most patients with [MCL].”

Understanding the interplay between immune-accompanying cells and malignant cells in the tumor microenvironment is important for selecting the best treatment option for patients with MCL, they concurred.