, while pretreatment mutational profiles offer clues as to which patients may respond to such anti-PD-1 treatments, according to studies presented at the European Society of Medical Oncology (ESMO) Congress 2023.
“We found that toripalimab combined with radiotherapy is safe and has promising efficacy for stage I/II extranodal NK/T cell lymphoma [patients] who have poor response after previous standard chemotherapy,” said first author Ming Jiang, MD, of the department of medical oncology, Cancer Center, West China School of Medicine/West China Hospital of Sichuan University, Chengdu, China.
“This combined strategy can not only improve patient efficacy but also avoid unnecessary medication, and is worth further exploration,” she said in a presentation at ESMO on Oct. 27 in Madrid. The current standard of care for extranodal NK/T cell lymphoma, a subtype of non-Hodgkin lymphoma, is L-asparaginase or pegaspargase-based multi-agent chemotherapy combined with radiotherapy.
However, for patients who fail to respond to first-line treatment, the prognosis is poor: The median progression-free survival of those patients is approximately 4.5 months, with a median overall survival of about 6.4 months, Dr. Jiang explained.
“There is a need to establish a better first-line treatment for this group of patients,” she said.
In the prospective, single-arm, multicenter phase 2 study, Dr. Jiang and her colleagues enrolled patients with stage 1 and 2 extranodal NK/T cell lymphoma who had failed to achieve a complete response following 2-3 cycles of multi-agent chemotherapy.
Of the patients, eight (36.4%) had partial response, eight (36.2%) had stable disease, and six (27.2%) had progressive disease after the chemotherapy.
The patients were treated with toripalimab at 240 mg, once every 3 weeks, plus radiotherapy at a dose of 56 Gy, sequentially with or without two to four cycles of chemotherapy.
Patients who did not have disease progression were then continued with toripalimab for 1 year or until disease progression or intolerable toxicity.
The 22 patients had a median age of 45 (range 26-64) and 14 were male. Most were stage 1 (77.3%; 17) and the remaining were stage 2, while 81% had primary tumor invasion.
For the primary endpoint, at 3 months following radiotherapy, the overall response rate was 90.9%, with 17 patients (77.3%) having a complete response, 3 (13.6%) a partial response, and 2 (9.1%) having progressive disease.
Eight who had responded to previous chemotherapy received two additional chemotherapy cycles after completion of radiotherapy, while the others were treated with toripalimab alone.
With a median follow-up of 23 months (range 3-78), the 2-year progression-free survival was 81.6%, and overall survival was 95.0%.
Two of three patients with a partial response had a recurrence after radiotherapy at 5 and 10 months; one of the complete-response patients had a recurrence at 60 months, and two patients with progressive disease died at 9 months after radiotherapy.
In terms of safety, the most common adverse events during and after radiotherapy included oral mucositis and hypothyroidism. No adverse events of grade 3 or higher were reported.
Dr. Jiang speculated that “radiotherapy could synergize PD-1 inhibitors,” and she urged that “optimal radiotherapy and PD-1 inhibitor administration plans should be further explored.”