Primary central nervous system lymphoma(PCNSL)is a rare and frequently fatal lymphoma subtype.The programmed death-1(PD-1)pathway has emerged as a potential therapeutic target,but the effectiveness of PD-1 antibody si...Primary central nervous system lymphoma(PCNSL)is a rare and frequently fatal lymphoma subtype.The programmed death-1(PD-1)pathway has emerged as a potential therapeutic target,but the effectiveness of PD-1 antibody sintilimab in combination with immunochemotherapy as a frontline treatment for PCNSL remains to be determined.In this phase 2 trial(ChiCTR1900027433)with a safety run-in,we included patients aged 18–70 with newly diagnosed PCNSL.Participants underwent six 21-day cycles of a SMTR regimen,which includes sintilimab(200 mg,Day 0),rituximab(375 mg/m2,Day 0),methotrexate(3.0 g/m2,Day 1 or 1.0 g/m2 for patients aged≥65 years),and temozolomide(150 mg/m2/d,Days 1–5).Among 27 evaluable patients,the overall response rate(ORR)was 96.3%(95%confidence interval:81–99.9%),with 25 complete responses.At a median follow-up of 24.4 months,the medians for duration of response,progression-free survival(PFS),and overall survival were not reached.The most common grade 3–4 treatment-related toxicities were increased levels of alanine aminotransferase(17.9%)and aspartate aminotransferase(14.3%).Additionally,baseline levels of interferon-αand the IL10/IL6 ratio in cerebrospinal fluid emerged as potential predictors of PFS,achieving areas under the curve of 0.88 and 0.84,respectively,at 2 years.Whole-exome sequencing revealed a higher prevalence of RTK-RAS and PI3K pathway mutations in the durable clinical benefit group,while a greater frequency of Notch and Hippo pathway mutations in the no durable benefit group.These findings suggest the SMTR regimen is highly efficacious and tolerable for newly diagnosed PCNSL,warranting further investigation.展开更多
基金https://doi.org/10.1038/s41392-024-01941-x Fujian Provincial Health Technology Project[grant number 2023CXA028]Joint Funds for the Innovation of Science and Technology,Fujian Province(grant number 2023Y9021)+2 种基金National Science Foundation of Fujian Province[grant number 2022J02036]Clinical research project of Wu Jieping Medical Foundation[grant number 320.6750.19094-41]National Natural Science Foundation of China[grant number 82070218,81400160].
文摘Primary central nervous system lymphoma(PCNSL)is a rare and frequently fatal lymphoma subtype.The programmed death-1(PD-1)pathway has emerged as a potential therapeutic target,but the effectiveness of PD-1 antibody sintilimab in combination with immunochemotherapy as a frontline treatment for PCNSL remains to be determined.In this phase 2 trial(ChiCTR1900027433)with a safety run-in,we included patients aged 18–70 with newly diagnosed PCNSL.Participants underwent six 21-day cycles of a SMTR regimen,which includes sintilimab(200 mg,Day 0),rituximab(375 mg/m2,Day 0),methotrexate(3.0 g/m2,Day 1 or 1.0 g/m2 for patients aged≥65 years),and temozolomide(150 mg/m2/d,Days 1–5).Among 27 evaluable patients,the overall response rate(ORR)was 96.3%(95%confidence interval:81–99.9%),with 25 complete responses.At a median follow-up of 24.4 months,the medians for duration of response,progression-free survival(PFS),and overall survival were not reached.The most common grade 3–4 treatment-related toxicities were increased levels of alanine aminotransferase(17.9%)and aspartate aminotransferase(14.3%).Additionally,baseline levels of interferon-αand the IL10/IL6 ratio in cerebrospinal fluid emerged as potential predictors of PFS,achieving areas under the curve of 0.88 and 0.84,respectively,at 2 years.Whole-exome sequencing revealed a higher prevalence of RTK-RAS and PI3K pathway mutations in the durable clinical benefit group,while a greater frequency of Notch and Hippo pathway mutations in the no durable benefit group.These findings suggest the SMTR regimen is highly efficacious and tolerable for newly diagnosed PCNSL,warranting further investigation.
