OBJECTIVES: Testing for poor prognostic factors such as del(17p) chromosomal anomaly, mutated TP53 or NOTCH1, and unmutated IGHV has significant relevance in guiding therapy in CLL as these markers have significant impact on outcomes and progression. Although, international and national guidelines are widely available, little is known about real-world testing. Here, we investigated real-world clinical practices on CLL prognostic testing in Belgium, France, Germany, Italy, the Netherlands, Spain, Sweden, and the United Kingdom.

METHODS: A systematic literature review covering 2015-2020 was conducted (PROSPERO-ID: CRD42021296570) focusing on routine practice, therefore research articles where genetic testing was protocol-driven were excluded. Proportions of tested CLL patients among full study cohorts were calculated. Information on reasons for not testing and real-world costs were collected. Qualitative and descriptive quantitative synthesis of extracted data was performed.

RESULTS: Of the identified 90 observational studies, 68%, 67%, 27%, 21%, and 10% reported routine screening data for IGHV mutation, del(17p), TP53 disruption, TP53 mutation, and NOTCH1 mutation, respectively. A trend of increased testing rates was observed over time, with highest growth in TP53 mutation testing. Routine testing rates in regional and country-level studies tended to be lower than rates reported for institutional studies. Studies enrolling relapse/refractory patients for testing appeared to be conducted more recently. Reasons for not testing all patients was reported only in a few sources. Information about the real-world cost of testing these markers was scarce.

CONCLUSIONS: We found a large number of studies reporting routine testing for IGHV mutational status and del(17p), less data on TP53 disruption/TP53 mutation, and sparse data on NOTCH1. Common reasons for not testing some patients in routine care could not be identified and require further elucidation. Testing rates were higher in studies conducted at institutional level than regional/country level studies; this difference was most apparent for tests requiring DNA sequencing.