LAUSR

The survival of chronic lymphocytic leukaemia (CLL) has been constantly improving over the years, as documented by populationbased studies, mainly including patients treated with chemoimmunotherapy. 3 During the last decade, the introduction of Bruton tyrosine kinase inhibitors (BTKi), targeting the Bcell receptor pathway, and of BCL2 inhibitors (BCL2i), targeting the apoptotic pathway, have led to major advances in CLL treatment and will further improve CLL outcomes. 6 In this rapidly evolving therapeutic landscape, the frequent update of clinical guidelines allows us to constantly standardise patient management in clinical practice and offers an important tool for improving patient outcomes. In their paper, Walewska et al. report on the update of the guidelines for the management of CLL by the British Society of Haematology (BSH). The updated BSH guidelines clearly take into account that CLL is a model for precision medicine. In fact, tumour protein p53 (TP53) disruption and the mutational status of immunoglobulin heavy chain (IGHV) genes are the backbone of treatment tailoring in this leukaemia. The worse outcome of TP53disrupted patients treated with chemoimmunotherapy has been documented in several randomised, phase III clinical trials, 11 and TP53disrupted patients are now treated with novel agents. Similarly, the mutational status of IGHV genes is also currently used for treatment tailoring. Consistently, the updated BSH CLL guidelines strongly recommend the assessment of TP53 and IGHV mutational status before starting treatment. The BSH guidelines righteously restrict the use of CLL predictive biomarkers to TP53 and IGHV analysis. In fact, several other predictive biomarkers are under scrutiny, but are not considered mature enough for inclusion in clinical guidelines. For instance, baculoviral IAP repeatcontaining 3 (BIRC3) mutations may identify patients who fail chemoimmunotherapy but may benefit from venetoclaxbased treatment stragies. In the future, a deeper understanding of CLL biomarkers may allow us to answer the currently open question of which biological agent should be best used based on the genotype of each single patient. In this respect, different ongoing trials comparing BTKi and BCL2i will provide new important evidence (Phase III GAIA/CLL13, ECOG EA9161, Alliance A041702 and CLL17 clinical trials). Infections have a major impact on the clinical course of CLL and the updated BSH guidelines clearly address this issue. The role of Pneumocystis jirovecii (PJP) prophylaxis has been clearly confirmed in CLL and patients under treatment should receive prophylaxis for at least 12 months. Conversely, conflicting results are still present regarding the role of prophylaxis with azoles. Importantly, this prophylaxis should be carefully evaluated especially in patients receiving venetoclax, due to the strong interaction in drug metabolism of this drug with azoles. Passive immunisation with immunoglobulins (Igs) deserves consideration in specific patients with CLL, and probably might be beneficial also in the case of IgG levels around the wellestablished cutoff of 4 g/l in the absence of recurrent infections. Future studies will clarify this issue. An important recommendation made by the updated BSH guidelines concerns vaccination in patients with CLL. The response to vaccines in CLL is lower than in the healthy population and active treatment lowers the immune response even further. This is particularly true in the case of vaccines against novel antigens that patients have not encountered before CLL development (e.g. hepatitis B virus). Therefore, patients should undergo vaccination early in the disease history Received: 16 February 2022 | Accepted: 18 February 2022