Standard-of-care therapies for patients with relapsed and/or refractory (R/R) chronic lymphocytic leukaemia (CLL) are shifting from being chemoimmunotherapy based to incorporating targeted agents such as venetoclax, an inhibitor of apoptotic regulator BCL-2. Now, updated results of the phase III MURANO trial confirm a progression-free survival (PFS) benefit with venetoclax in CLL.

Patients with R/R CLL were randomly assigned to receive either 6 cycles of venetoclax plus rituximab and then venetoclax monotherapy for an additional 18 months (fixed-duration regimen; n = 194) or 6 cycles of bendamustine plus rituximab (standard regimen; n = 195). In an earlier analysis (median follow-up duration of 23.8 months), PFS was superior with the fixed-duration regimen over standard therapy. “At the time of analysis, most patients were still receiving venetoclax. The question was whether survival curves would remain favourable after treatment cessation,” explains lead investigator Arnon Kater.

For the 130 patients (65%) who completed treatment with venetoclax, the median duration of treatment was 24.4 months. At a median follow-up duration of 36.0 months, PFS remained longer with the fixed-duration regimen than with standard treatment: not reached versus 17.0 months (HR 0.16; P < 0.001). The estimated 3-year overall survival was 87.9% versus 79.5%. In the earlier publication, the reported frequencies of grade 3–4 adverse events were 82.0% with the fixed-duration regimen and 70.2% with the standard regimen.

A secondary end point of the study was the assessment of minimal residual disease (MRD) in peripheral blood 2–3 months after the end of combination therapy. The rate of undetectable MRD (<1 CLL cell per 104 leukocytes) was substantially higher with the fixed-duration than with the standard regimen (82.5% versus 23.1%). In either treatment arm, PFS durations were longer for patients with undetectable MRD than for those with detectable MRD. “Our results indicate that undetectable or low levels of MRD (1 CLL cell per 102–104 leukocytes) are meaningful end points and a desirable goal of CLL therapies,” summarizes Kater.

undetectable or low levels of MRD … [are] a desirable goal of CLL therapies

On the importance of these results, Kater adds “Findings on MRD provide data that will be implemented in new trials aiming to investigate limiting the length of fixed-duration therapy. This aspect is highly desired by both patients and health authorities owing to the long-term toxicities (including financial toxicities) associated with maintenance therapy.”