Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL)
Reason for review: There has been significant advances in treating relapsed/refractory chronic lymphocytic leukemia (CLL) in the last 2 decades. However, the aim of treatment remains charge of the condition and delay of progression as opposed to a cure which remains largely elusive. Thinking about that CLL is mainly observed in older patients, you will find multiple factors that lead to selecting CLL past the frontline treatment. Here, we review the idea of relapsed CLL, factors that predispose to relapse, and therapeutic possibilities for this patient population. We review investigational therapies and supply a framework for choice of therapies within this setting.
Recent findings: Targeted therapies with continuous BTK inhibitors (BTKi) or fixed duration venetoclax plus anti-CD20 monoclonal antibody therapy established brilliance over chemoimmunotherapy in relapsed CLL and also have end up being the preferred standard of care treatment. The 2nd-generation more selective BTK inhibitors (acalabrutinib and zanubrutinib) have proven improved safety profile when compared with ibrutinib. However, potential to deal with the covalent BTK inhibitors may emerge and it is generally connected with mutations in BTK or any other downstream enzymes. The novel non-covalent BTK inhibitors for example pirtobrutinib (Loxo-305) and nemtabrutinib (ARQ 531) are showing promising activities for relapsed CLL refractory to prior covalent BTKi. Other novel therapies for example chimeric antigen receptor (Vehicle) T cell therapy also have proven significant activities for relapsed and refractory CLL. Measurable residual disease (MRD) assessment includes a growing importance in venetoclax-based limited-duration therapy and there’s mounting evidence that MRD negativity improves outcomes. However, it remains seen if the will end up a recognised clinically significant endpoint. Further, the perfect sequence of numerous treatments remains determined. Patients with relapsed CLL are in possession of more options to treat the condition. The option of treatments are best individualized especially even without the direct comparisons of targeted therapies, and in the future brings more data around the best sequence of utilisation of the therapeutic agents.