Activity of pembrolizumab in relapsed/refractory NK/T-cell lymphoma

Abstract

Natural killer/T-cell lymphoma (NKTCL) is a rare subtype of non-Hodgkin lymphoma that is associated with a poor outcome. Currently, the treatment needs of NKTCL remain unmet, and efforts to further improve treatment are urgently needed. Herein, seven patients with NKTCL who failed to respond to various types of chemotherapies were treated with the anti-programmed death 1 (anti-PD-1) antibody pembrolizumab at 100 mg every 3 weeks. After a median of four cycles of treatment (range 2-18), four out of seven patients responded (two complete response, two partial response, overall response rate 57%). Expression of PD1-ligand available was 50, 20, 30, 70, and 30% of five patients respectively. It is negative in one patient and not tested in one patient. Adverse events, which mostly ranged from grade I to grade III, were tolerable and could be safely handled, although immune-related pneumonitis was notable. Overall, PD-1 blockade with pembrolizumab represents a favorable strategy for the treatment of refractory/relapsed NKTCL.

Keywords: NK/T-cell lymphoma; PD-1 blockade; Pembrolizumab.

Fig. 1

Lesion changes of case 1 before and after pembrolizumab treatment. a The skin lesions of lower limbs of case 1 at the time of relapse. b The skin lesions responded after the first cycle. After 4 cycles, her crust of the lesions fell off and ulcers healed

Fig. 2

Changes in circulating EBV DNA with pembrolizumab treatment. The EBV DNA levels in case 2 fell from 1330 copies/ml to < 500 copies/ml after 5 cycles. The EBV DNA levels in case 3 fell from 1390 copies/ml to < 500 copies/ml after 3 cycles. The EBV DNA levels in case 5 rose from normality to 2140 copies/ml after 2 cycles and went back to normal 4 cycles later. The EBV DNA levels of case 6 rose from 22,100 copies/ml to 224,000 copies/ml after 3 cycles. The EBV DNA levels of case 7 rose gradually from 10,900 copies/ml to 190,000 copies/ml prior to pembrolizumab treatment

Fig. 3

PET/CT results of case 2. The scan of case 2 in the left two images showed a relatively hypermetabolic lesion in mediastinal, hilar lymph nodes, and intestines after using pembrolizumab for 1 cycle. The two images on the right showed that the lesions were metabolically less active 2 cycles later

Fig. 4

HE staining and IHC of six patients available. The scan of case 2 in the left two images showed a relatively hypermetabolic lesion in mediastinal, hilar lymph nodes, and intestines after using pembrolizumab for 1 cycle. The two images on the right showed that the lesions were metabolically less active 2 cycles later