Prognostic factors in chronic lymphocytic leukaemia – the old, the new and the future

Prognostic assessment in chronic lymphocytic leukemia (CLL) is essential for delivery of timely, personalized therapy. TP53 status, karyotype, IGHV mutational status, minimal residual disease (MRD), gene mutations and markers of cell proliferation were important prognostic tools in the era of chemo-immunotherapy (CIT). With BCL2 inhibitors (BCL2i), outcome is still impacted by IGHV status, TP53 status, complex karyotype, and achievement of undetectable MRD. On the other hand, BTK inhibitors (BTKi) are agnostic to IGHV status, rarely cause MRD negative remissions and are less clearly impacted by TP53 status. Although based on less mature data, outcomes with BCL2i/BTKi combinations are likely influenced by TP53 and IGHV status. Responses to non-covalent BTKI (ncBTKI) are impacted by the mechanism of resistance to previous covalent BTKi. Finally, responses to chimeric antigen receptor T cell therapy (CAR-T) appear independent of TP53 status, but dependent on overall T- cell fitness.