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Sintilimab (anti-PD-1 antibody) combined with high-dose methotrexate, temozolomide, and rituximab (anti-CD20 antibody) in primary central nervous system lymphoma: a phase 2 study.
- Source :
-
Signal transduction and targeted therapy [Signal Transduct Target Ther] 2024 Sep 04; Vol. 9 (1), pp. 229. Date of Electronic Publication: 2024 Sep 04. - Publication Year :
- 2024
-
Abstract
- 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/m <superscript>2</superscript> , Day 0), methotrexate (3.0 g/m <superscript>2</superscript> , Day 1 or 1.0 g/m <superscript>2</superscript> for patients aged ≥65 years), and temozolomide (150 mg/m <superscript>2</superscript> /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-α and 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.<br /> (© 2024. The Author(s).)
- Subjects :
- Humans
Male
Female
Middle Aged
Aged
Adult
Lymphoma drug therapy
Lymphoma genetics
Lymphoma immunology
Methotrexate administration & dosage
Methotrexate therapeutic use
Antineoplastic Combined Chemotherapy Protocols therapeutic use
Antineoplastic Combined Chemotherapy Protocols pharmacology
Antineoplastic Combined Chemotherapy Protocols administration & dosage
Rituximab administration & dosage
Temozolomide administration & dosage
Temozolomide pharmacology
Central Nervous System Neoplasms drug therapy
Central Nervous System Neoplasms genetics
Central Nervous System Neoplasms immunology
Antibodies, Monoclonal, Humanized administration & dosage
Antibodies, Monoclonal, Humanized therapeutic use
Antibodies, Monoclonal, Humanized pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 2059-3635
- Volume :
- 9
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Signal transduction and targeted therapy
- Publication Type :
- Academic Journal
- Accession number :
- 39227388
- Full Text :
- https://doi.org/10.1038/s41392-024-01941-x