Early findings from the CLARITY trial, published in the Journal of Clinical Oncology, demonstrate encouraging survival benefits with the combination of ibrutinib plus venetoclax for relapsed and refractory chronic lymphocytic leukaemia (CLL).
The phase 2 trial combined ibrutinib with venetoclax to eradicate detectable CLL with the intention of stopping therapy. The primary endpoint was eradication of measurable residual disease (MRD) after 12 months of combined therapy. Key secondary endpoints were response by International Workshop on CLL criteria, safety, and progression-free (PFS) and overall survival (OS).
After 12 months of combination therapy, MDR negativity (fewer than one CLL cell in 10,000 leukocytes) was achieved in the blood of 28 of 53 patients (52.8%) and the marrow of 19 (35.8%).
Forty-seven patients (89%) demonstrated response to treatment, with 27 (51%) achieving complete remission.
After a median follow-up of 21.1 months, one patient had progressed and all patients were alive. A single case of biochemical tumour lysis syndrome was observed. Other adverse effects were mild and/or manageable and most commonly were neutropenia or gastrointestinal events.
The authors said: “The observation that a significant proportion of patients experience MRD-negative remission indicates that this combination can be given for a limited period and then stopped after patients achieve a deep remission. This observation is critical before taking the MRD-guided approach into larger phase 3 trials.” However, they also noted that whether or not the combination leads to permanent disease eradication remains to be seen.