A recent trial of an all-tablet treatment found superior progression-free survival compared to chemoimmunotherapy.
Chronic lymphocytic leukaemia patients may no longer need to undergo lengthy infusions that cause immune suppression and other nasty side effects.
Chemoimmunotherapy has been replaced as the standard treatment for chronic lymphocytic leukaemia by more targeted therapies like acalabrutinib, venetoclax and obinutuzumab. However, it is unclear whether these all-oral treatments result in better outcomes.
But the results of a new study, published in the New England Journal of Medicine, reports that patients given the acalabrutinib-venetoclax treatment were 35% less likely to experience disease progression or death after three years compared to patients who received chemoimmunotherapy.
“[These results] show the potential to achieve better outcomes for patients through a simple tablet-based therapy, rather than requiring them to come to hospital and receive their treatment via an infusion,” said Professor John Seymour, director of haematology at the Peter MacCallum Cancer Centre and the Royal Melbourne Hospital.
Researchers from over 100 hospitals across 27 countries – including the Peter Mac – recruited 725 adult patients with previously untreated CLL as part of the AMPLIFY trial, where patients received an acalabrutinib-venetoclax combination (with or without obinutuzumab) or standard chemoimmunotherapy.
The proportion of patients with progression-free survival at 36 months was higher in patients receiving acalabrutinib-venetoclax (77%) and acalabrutinib-venetoclax-obinutuzuman (83%) compared to chemoimmunotherapy (65-69%, depending on the specific regimen employed).
Overall survival at three years was also similar after treatment with acalabrutinib-venetoclax (94%) and acalabrutinib-venetoclax-obinutuzumab (88%) compared to chemoimmunotherapy (86%), although patients receiving acalabrutinib-venetoclax were 67% less likely to die compared to patients receiving chemoimmunotherapy (adjusted hazard ratio 0.33, 95% confidence interval 0.18-0.56). There was no improvement on overall survival for the acalabrutinib-venetoclax-obinutuzumab-treated patients compared to the chemoimmunotherapy patients.
“This difference [in overall versus progression free survival] was largely driven by deaths due to covid in the acalabrutinib-venetoclax-obinutuzumab group early in the pandemic,” the researchers noted in the discussion.
Subgroup analyses also revealed that patients with an unmutated immunoglobulin heavy chain variable region – who typically have worse outcomes than patients with a IGHV mutation – had similar progression-free survival to the patients with a mutation.
“These patients had equivalent outcomes with the new combination, identifying this group as one that particularly benefits… which is promising in this hard-to-treat cancer group. It was also reassuring to observe similar side-effect profiles for all the treatments with the majority being readily manageable,” Professor Seymour said.
Professor Seymour said the risk of heart complications were much lower with the acalabrutinib-venetoclax combination used in the current study, compared to the currently approved all-tablet treatment that includes ibrutinib.
“Although the most common grade 3 or 4 adverse event in each group was generally manageable neutropenia… the acalabrutinib-venetoclax group had the fewest grade 3 or higher adverse events; few patients had overall atrial fibrillation or hypertension,” the researchers wrote.
Professor Seymour was hopeful that the acalabrutinib-venetoclax treatment would be accessible to CLL patients across the nation sooner rather than later.
“This really is wonderful news for fit, treatment-naive CLL patients and once this combination receives PBS-funding in Australia, we look forward to being able to offer them this safe and effective all-oral, fixed-duration regimen to reduce the burdens of therapy in the near future,” he said.
