PCNSL MSK Ibrutinib Phase I/II Cohort (2024)

Overview

Single-center phase I/II trial cohort (NCT02315326) at Memorial Sloan Kettering of 46 patients with relapsed/refractory CNS lymphoma treated with single-agent ibrutinib, with paired tumor and CSF genomic profiling PMID:38995739.

Composition

• 46 patients with r/r CNS lymphoma: 31 PCNSL + 15 SCNSL (secondary CNS DLBCLNOS); median age 68 (range 21–90); median 2 prior therapies; all previously received methotrexate PMID:38995739.
• Archival tumor biopsies sequenced in 25/31 PCNSL cases; paired pre-/on-treatment CSF (CSF1/CSF2) available for 14 patients PMID:38995739.

Assays / panels (linked)

• MSK-HemePACT — 585-gene hematologic-focused targeted panel on tumor and CSF ctDNA with matched germline PMID:38995739.
• MSK-IMPACT — used in independent MSK PCNSL SOC cohort for comparison PMID:38995739.

Papers using this cohort

• PMID:38995739 — Grommes et al., Clin Cancer Res 2024. Phase II long-term ibrutinib in r/r CNS lymphoma.

Notable findings derived from this cohort

• BCR-pathway alteration landscape: MYD88 72%, CD79B 48%, CARD11 24%, TBL1XR1 36%; 84% non-germinal center by Hans classifier PMID:38995739.
• TBL1XR1 WD40-domain mutations predicted prolonged ibrutinib PFS (16.5 vs 3.1 months, p=0.0075) PMID:38995739.
• MYD88 mutation associated with longer PFS on ibrutinib (9.2 vs 2.9 months, p=0.027); CARD11 mutation with shorter PFS (2.2 vs 5.5 months) PMID:38995739.
• CSF ctDNA clearance within 4 weeks correlated with complete and long-term ibrutinib response PMID:38995739.

Sources

• cBioPortal study: https://www.cbioportal.org/study/summary?id=pcnsl_msk_2024

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