Treatment will depend on the features of recurrent disease, previous management and the patient’s preferences.

In managing people with CLL, treatment may include these options: targeted agents (generally the preferred approach), repeat chemo-immunotherapy, investigational treatment on clinical trials or allogeneic bone marrow transplantation.

In some patients the disease is unlikely to respond well to second-line chemoimmunotherapy. This includes patients whose disease didn’t respond to first-line chemoimmunotherapy, patients who experienced disease progression within two to three years after first-line fludarabine-based chemoimmunotherapy, and those with leukaemia cells with del(17p) or TP53 mutations. If abnormalities were not previously detected, it is important to reassess TP53 status (by FISH and

sequencing) at each episode of disease recurrence/progression (Eichhorst et al. 2021; Hallek et al. 2018). Options for these patients are:

• non-chemotherapy regimens such as continuous BTK inhibitors (Byrd et al. 2016; 2019) or two years’ time-limited venetoclax and rituximab (Seymour et 2018)
• an oral PI3 kinase inhibitor such as idelalisib with rituximab (Sharman et 2019)
• entering a clinical trial if one is available
• in some highly selected cases, allogeneic hematopoietic stem cell

The potential goals of treatment should be discussed, respecting the patient’s cultural values. Wherever possible, written information should be provided.

Encourage early referral to clinical trials or accepting an invitation to participate in research.