Combination of Anti-PD-1 Antibody, Anlotinib and Pegaspargase “Sandwich” With Radiotherapy in Localized Natural Killer/T Cell Lymphoma

Abstract

Asparaginase/pegaspargase containing regimens combined with radiotherapy are highly effective and considered the cornerstone of localized Natural killer/T-cell lymphoma (NKTL) treatment. However, these chemotherapy regimens inevitably cause relatively high incidence of treatment-related adverse events (TRAEs). Herein we retrospectively evaluated the efficacy and safety of the combined regimen of anti-PD-1 antibody, anlotinib and pegaspargase “sandwich” with radiotherapy in localized NKTL. Anti-PD-1 antibody and pegaspargase at 2500 U/m2 were administered on day 1, while anlotinib (12 mg once a day) was orally administered on days 1-14. The treatment was repeated every 3 weeks. All the eight patients included received 3 cycles of the regimen followed by radiotherapy and an additional 3 cycles. The overall response rate was 100%, and the complete response rate was 87.5%. With a median follow-up time of 35.5 months (range, 34.03-40.90 months), median PFS and OS times were not reached. The 3-year PFS and OS rates were 100% and 100%, respectively. All patients were alive at the last follow-up. No treatment-related death and no grade 4 TRAE was reported. No grade 3/4 hematological toxicity was detected, and half of the patients didn’t report any hematological toxicity. This study indicates that anti-PD-1 antibody combined with anlotinib and pegaspargase is a promising chemoradiotherapy regimen for localized NTKL, with mild toxicity and good tolerance.

Treatment of extranodal NK/T-cell lymphoma: From past to future

“…In 2005, ENKTCL cells were found to be selectively sensitive to L-Asp ( 25 ), but long-term survivors were still rare in patients with advanced-stage disease until the introduction of programmed cell death protein 1 (PD-1) and its ligand (PD-L1) blockade immunotherapy in recent years. PD-1 blockade was reported to be highly active in relapsed/refractory (R/R) ENKTCL patients in 2017 ( 26 ) and later used to treat newly diagnosed early-stage disease in 2022 ( 27 ). The milestones in the recognition and treatment of ENKTCL are summarized in Figure 1 .…”

“…The area of each marker in the figure indicates the sample size of the study. Data are cited from ( 27 – 97 ).…”

“…CT, chemotherapy; RT, radiotherapy; Anth, anthracycline; CRT, chemoradiotherapy; Asp, asparaginase; PEG-Asp, pegaspargase; OS, overall survival. Data cited from ( 4 , 27 – 32 , 34 – 37 , 39 , 40 , 42 – 46 , 48 – 82 , 84 – 97 ).…”

“…Given the trend towards more simplified CT, the feasibility of concurrent CRT should be reevaluated. Recent studies have showed that Asp alone or Asp combined with immunotherapy also yielded excellent efficacy in patients with early-stage ENKTCL when combined with RT ( 27 , 67 ). These studies, although using small sample sizes, suggest that more simplified, more effective, and less toxic regimens are feasible.…”

“…recently reported the results of a retrospective study of early-stage ENKTCL treated with PEG-Asp combined with a PD-1 inhibitor, anlotinib (a multi-tyrosine kinase inhibitor approved in China for lung cancer), and sequential RT. Patient outcomes were excellent, with 100% 3-year PFS and OS, but a limitation of the study was that only 8 patients were included ( 27 ). The role of anlotinib in this combination was unknown, but the combination of the two most powerful ENKTCL drugs (PEG-Asp and PD-1 inhibitor) deserves further investigation in more patients.…”