Survival gains with acalabrutinib greater than other therapies for chronic lymphocytic leukaemia

Patients with chronic lymphocytic leukaemia (CLL) are better off with acalabrutinib than other therapies, with the drug ranking highest in treatment efficacy according to the results of a network meta-analysis (NMA).

The NMA used data from eight randomized clinical trials (RCTs) to evaluate the effect of acalabrutinib from ELEVATE-TN (study of Obinutuzumab + Chlorambucil, Acalabrutinib [ACP-196] + Obinutuzumab, and Acalabrutinib in Subjects With Previously Untreated CLL) against other therapies, namely bendamustine + rituximab, chlorambucil-based therapy, alemtuzumab, ibrutinib mono/combination therapy, and venetoclax + obinutuzumab.

There were two evidence networks created: network A, which comprised solely of RCTs that met the inclusion criteria; and network B, which was composed of seven RCTs and a published cross-trial comparison of ibrutinib from RESONATE-2 and chlorambucil + obinutuzumab from iLLUMINATE.

In both networks, the acalabrutinib + obinutuzumab regimen showed superiority over all comparators in terms of progression-free survival (PFS) improvement.

Acalabrutinib monotherapy also conferred significant PFS gains vs most comparators, such as ibrutinib monotherapy in network A only and venetoclax + obinutuzumab in network B only.

Additionally, overall survival (OS) was more favourable with acalabrutinib vs all other comparators, but the differences were not significant, with the estimates indicating a high level of uncertainty.

Acalabrutinib + obinutuzumab was the top-ranking regimen with respect to the PFS outcome (surface under the cumulative ranking area [SUCRA] values, 98 percent and 100 percent in networks A and B, respectively) and OS improvement (SUCRA values, 92 percent and 94 percent, respectively). Acalabrutinib monotherapy followed closely after, with SUCRA values of 88 percent and 90 percent for PFS and 83 percent and 87 percent for OS, in networks A and B, respectively.

Despite the presence of several limitations, such as the heterogeneity of baseline characteristics across trials, variable treatment regimens, and short study follow-up times, the NMA offers insights into the relative efficacy of acalabrutinib vs frontline CLL therapies in the absence of head-to-head clinical trials.