NICE has published new draft guidance which recommends acalabrutinib as an option for untreated chronic lymphocytic leukaemia (CLL) in adults with a 17p deletion or TP53 mutation, and those who have had at least one previous treatment, if ibrutinib is their only suitable treatment option.
The decision is based on results for the population with untreated CLL from ELEVATE-TN, an open-label randomised controlled trial (RCT) comparing acalabrutinib monotherapy (n=179) with chlorambucil plus obinutuzumab (n=177). ELEVATE-TN included people over 18 years with untreated CLL whose multimorbidities made fludarabine, cyclophosphamide, and rituximab (FCR) or bendamustine plus rituximab (BR) unsuitable.
People in ELEVATE-TN had to have a Cumulative Illness Rating Scale score > 6 or a creatinine clearance <70 ml/min, which would mean that FCR or BR would be unsuitable for similar patients in NHS clinical practice. Of the 356 people in ELEVATE-TN, 35 had a 17p deletion or TP53 mutation.
After a median follow-up of 28 months, there was a statistically significant increase in progression-free survival (PFS) for acalabrutinib compared with chlorambucil plus obinutuzumab (hazard ratio [HR] 0.20; 95% CI 0.13-0.30; P<0.0001). Median PFS was not reached in the acalabrutinib arm and was 22.6 months in the chlorambucil plus obinutuzumab arm. Median time to next treatment was not reached in either treatment arm but the trend was towards this being longer with acalabrutinib.
Data on overall survival were immature. Median OS was not reached in either treatment arm and there was no difference in overall survival between the two arms (HR 0.60; 95% CI 0.28-1.27; P=0.1556).
The results of ELEVATE-TN showed that acalabrutinib had an acceptable tolerability profile compared with chlorambucil plus obinutuzumab.
Given the current uncertainties about subsequent treatment costs and survival estimates, the incremental cost-effectiveness ratio (ICER) for acalabrutinib was not considered an acceptable use of NHS resources for untreated CLL that is not high-risk and when FCR or BR is unsuitable. Acalabrutinib is not recommended for routine use in the NHS for this population.
The draft guidance is now open for public consultation. Closing date for receipt of comments is 5 pm, Monday, January 11, 2021.
