Platform Research for Innovative Medicines in NF2-SWN (PRIME-NF2)

Other illness

• Coexisting other genetic syndromes that may cause multiple intracranial tumors (e.g., SMARCB1/LZTR1-related schwannomatosis, Cowden syndrome);
• Presence of severe psychiatric disorders or cognitive impairment that precludes cooperation with imaging or hearing assessments;
• Sub-study-specific exclusion criteria (for intervention arms only): If the subject intends to enter an interventional sub-study, the subject must also satisfy the specific exclusion criteria specified in that sub-study protocol (e.g., specific organ dysfunction, active infection, pregnancy, etc.).

Other

• Subjects meeting any of the following criteria will not be permitted to enter the main study:
• Expected survival \<12 months;
• Extreme social or geographic factors that, in the investigator's judgment, may impede follow-up for more than 12 months;

• Subjects must satisfy all of the following criteria to be enrolled into the main study natural history observation cohort:
• (1) Must meet the 2022 International Consensus Criteria for NF2-SWN, defined by having at least one of the following:
• Bilateral vestibular schwannomas (VS)
• An identical NF2 pathogenic variant in at least 2 anatomically distinct NF2-related tumors (schwannoma, meningioma, and/or ependymoma). (Note: if the variant allele fraction (VAF) in unaffected tissues such as blood is clearly \<50%, the diagnosis is mosaic NF2-related schwannomatosis)
• Either 2 major or 1 major and 2 minor criteria as described in the following:
  • Major criteria:
• Unilateral VS
• First-degree relative other than sibling with NF2-related schwannomatosis
• 2 or more meningiomas (Note: single meningioma qualifies as minor criteria).
• NF2 pathogenic variant in an unaffected tissue such as blood (Note: if the VAF is clearly \<50%, the diagnosis is mosaic NF2-related schwannomatosis)
  • Minor criteria:
  • Can count \>1 of a type (eg, 2 distinct schwannomas would count as 2 minor criteria)
• Ependymoma, meningioma (Note: multiple meningiomas qualify as a major criteria), schwannoma (Note: if the major criterion is unilateral VS, at least 1 schwannoma must be dermal in location) Can count only once (eg, bilateral cortical cataracts count as a single minor criterion)
• Juvenile subcapsular or cortical cataract, retinal hamartoma, epiretinal membrane in a person aged \<40 years, meningioma
  • (2) Presence of at least one evaluable lesion: Vestibular schwannoma, meningioma, or non-vestibular schwannoma: clearly identifiable lesion on contrast-enhanced T1-weighted MRI; Ependymoma: clearly identifiable lesion on contrast-enhanced T1-weighted or T2/FLAIR sequences; (3) Expected ability to complete at least 12 months of follow-up assessments; (4) Ability to understand and voluntarily sign a written informed consent form, or a legally authorized guardian signs the informed consent form together ; (5) Sub-study-specific criteria (for intervention arms only): If the subject intends to enter an interventional sub-study, in addition to meeting the above main study criteria, the subject must also satisfy the specific inclusion criteria specified in that sub-study protocol (e.g., organ function, prior treatment restrictions, washout periods, etc.), as determined by the drug characteristics.

Criteria the registry did not label

• Eligibility Specific For MASTER STUDY