A Prospective Phase II Clinical Trial Using Chidamide, Tislelizumab, and Pegaspargase (CTP regimen) in Combination with Radiotherapy As First-Line Treatment in High-Risk Stages I and II of Extranodal NK/T-Cell Lymphoma

Background:

At present, there is no standardized treatment regimen for early-stage extranodal natural killer/T-cell lymphoma (ENKTL). Induction chemotherapy based on pegaspargase, followed by radiotherapy, often leads to more favorable therapeutic outcomes. However, about 30-40% of patients still do not achieve complete remission (CR), particularly those with high-risk factors. Moreover, these treatment approaches can cause severe myelotoxicity and gastrointestinal toxicity, which subsequently reduce the rate of treatment completion and patient compliance.

Aims:

To investigate the efficacy and safety of chidamide, tislelizumab, and pegaspargase in combination with radiotherapy as first-line treatment in high-risk stage I/II ENKTL.

Methods:

Patients with untreated, pathologically confirmed ENKTL, classified as stage I with at least one high-risk factor or stage II according to the Ann Arbor staging system, were enrolled. After they received four cycles of induction treatment, the patients who were evaluated as partial response (PR) or CR underwent sequential radiotherapy, followed by two additional cycles of induction therapy.

The induction therapy regimen was as follows: chidamide, 20 mg PO, BIW; tislelizumab, 200 mg iv, D1; and pegaspargase, 2,000 U/m² im, D1; 21 days/cycle. Intensity-modulated radiation therapy (IMRT) was used for radiotherapy. The primary study endpoints were the complete response rate (CRR) and objective response rate (ORR) after completing six cycles of induction therapy. The secondary study endpoints were progression-free survival (PFS), overall survival (OS), and safety.

Results:

Between March 2020 and March 2022, 37 patients were enrolled, whose median age was 51 (age range 20-72). Patients at stage I with high-risk factors accounted for 54.1% (20/37), and patients at stage II accounted for 45.9% (17/37). A total of 18 patients had a PINK-E score of 1 (48.6%), and the others had a score of 0 (51.4%) (Table 1). Efficacy evaluations were available for 28 patients (75.7%). The dose of chidamide was adjusted from 20 mg BIW to 5 mg PO QD in two cases because of digestive tract reactions, and in 14 cases, the initial usage of chidamide was adjusted to 5 mg QD in the whole process. The other patients followed the originally designed plan. There were 28 patients who obtained at least one therapeutic efficacy evaluation before radiation, whose ORR was 89.3% (25/28) and CRR was 71.4% (20/28). For the 24 patients who eventually completed the treatment regimen of CTP and radiotherapy, CRR and ORR were both 100%. For the 28 patients evaluable for efficacy, the median follow-up time was 36.5 months, and the median PFS and OS were both not reached. The 3-year PFS rate was estimated to be 81.2%, and the 3-year OS rate was 88.6%. The grade 3/4 hematologic AEs with incidence >5% were neutropenia (3/37, 8.1%), anemia (2/37, 5.4%), and thrombocytopenia (2/37, 5.4%). The grade 3/4 non-hematologic AEs were elevated ALT/AST (6/37, 16.2%) and upper gastrointestinal hemorrhage (2/37, 5.4%) (Table 2). There were five patients (13.5%) who terminated treatment or changed regimen because of AEs. The incidence rate of immune-related AEs was 40.5% (15/37), among which the incidence rate of grade 3 immune-related AEs was 8.1%.

Conclusion:

The CTP regimen in combination with radiotherapy as first-line treatment preliminarily indicated effectiveness for ENKTL at high-risk stages I and II. The patients had high CRR, PFS rate, OS rate and controllable adverse reactions. (NCT04414969)

No relevant conflicts of interest to declare.