Risk‐based, response‐adapted therapy for early‐stage extranodal nasal‐type NK/T‐cell lymphoma in the modern chemotherapy era: A China Lymphoma Collaborative Group study

Abstract

We aimed to determine the survival benefits of chemotherapy (CT) added to radiotherapy (RT) in different risk groups of patients with early‐stage extranodal nasal‐type NK/T‐cell lymphoma (ENKTCL), and to investigate the risk of postponing RT based on induction CT responses. A total of 1360 patients who received RT with or without new‐regimen CT from 20 institutions were retrospectively reviewed. The patients had received RT alone, RT followed by CT (RT + CT), or CT followed by RT (CT + RT). The patients were stratified into different risk groups using the nomogram‐revised risk index (NRI). A comparative study was performed using propensity score‐matched (PSM) analysis. Adding new‐regimen CT to RT (vs RT alone) significantly improved overall survival (OS, 73.2% vs 60.9%, P < .001) and progression‐free survival (PFS, 63.5% vs 54.2%, P < .001) for intermediate‐risk/high‐risk patients, but not for low‐risk patients. For intermediate‐risk/high‐risk patients, RT + CT and CT + RT resulted in non‐significantly different OS (77.7% vs 72.4%; P = .290) and PFS (67.1% vs 63.1%; P = .592). For patients with complete response (CR) after induction CT, initiation of RT within or beyond three cycles of CT resulted in similar OS (78.2% vs 81.7%, P = .915) and PFS (68.2% vs 69.9%, P = .519). For patients without CR, early RT resulted in better PFS (63.4% vs 47.6%, P = .019) than late RT. Risk‐based, response‐adapted therapy involving early RT combined with CT is a viable, effective strategy for intermediate‐risk/high‐risk early‐stage patients with ENKTCL in the modern treatment era.

Progression-free survival at 24 months and subsequent survival of patients with extranodal NK/T-cell lymphoma: a China Lymphoma Collaborative Group (CLCG) study

“…Furthermore, there is an urgent requirement to identify patients at high risk of early progression who would benefit from innovative treatment strategies. Following the achievement of PFS24, research for ENKTCL survivors should focus on lessintensive surveillance, long-term treatment toxicity, quality of life, and other outcomes [34,37,38]. Previous studies, mainly using the randomized controlled trial (RCT) or real-world data, have demonstrated that the surrogate endpoints of EFS and PFS are strongly related to OS at both trial-and individual-level in different lymphoma subtypes [26-29, 32, 39-41].…”

“…Furthermore, there is an urgent requirement to identify patients at high risk of early progression who would benefit from innovative treatment strategies. Following the achievement of PFS24, research for ENKTCL survivors should focus on less-intensive surveillance, long-term treatment toxicity, quality of life, and other outcomes [ 34 , 37 , 38 ].…”

Association of improved overall survival with decreased distant metastasis following asparaginase-based chemotherapy and radiotherapy for intermediate- and high-risk early-stage extranodal nasal-type NK/T-cell lymphoma: a CLCG study

“…[9][10][11][12][13][14][15][16][17][18] Given favorable outcomes with upfront radiotherapy for early-stage ENKTCL, adding chemotherapy to radiotherapy conferred survival benefit for intermediate-and high-risk patients but not for low-risk patients. 22,23 A variety of ASP-based or PLA-based regimens have been used as the appropriate CMT approach. [24][25][26][27][28][29][30][31][32][33][34][35][36][37] There are no comparative data describing the benefit of ASP-based regimens over non-ASP-based regimens for early-stage ENKTCL.…”

“…The sequencing strategy for chemotherapy and radiotherapy in early-stage ENKTCL varies across countries and between collaborative study groups. 11,23,46,47 In a recent CLCG study of 1360 NRI-stratified early-stage patients, the sequence and optimal cycles of non-anthracycline-based chemotherapy have been especially addressed in the setting of radiotherapy. 23 For intermediate-and high-risk patients treated with sequential chemoradiotherapy, radiotherapy-first CMT showed similar 5-year OS (77.7% versus 72.4%; P ¼ 0.290) and PFS (67.1% versus 63.1%; P ¼ 0.592) to chemotherapy-first CMT.…”

“…20,21 Adding chemotherapy to radiotherapy provides survival benefit in intermediate-and high-risk early-stage patients, 22 even in the modern chemotherapy era. 23 In the setting of CMT, both ASP-based and non-ASP-based (mainly PLA-based) regimens are considered an option for early-stage patients. [24][25][26][27][28][29][30][31][32][33][34][35][36][37] Usually, ASP-based regimens, such as modified SMILE, 13,24 GELOX (GEM, oxaliplatin, L-ASP), [25][26][27][28] P-GEMOX (pegaspargase, GEM, oxaliplatin), 27,28 VIDL (etoposide, ifosfamide, cisplatin, L-ASP), 29 LVP/D (L-ASP, vincristine, prednisone/dexamethasone), [30][31][32] MESA (MTX, etoposide, dexamethasone, pegaspargase), 33 and GDP-L/P (GEM, dexamethasone, cisplatin, L-ASP, or pegaspargase) 16,34 are administrated subsequently with radiotherapy.…”