Prof. Hallek opened his talk with the reminder that CLL treatment is already a pioneering chemotherapy-free regimen. To this end, Prof. Hallek went on to highlight the numerous novel therapies targeting specific pathways in CLL (Bruton’s tyrosine kinase, PI3-Kinase, and Lyn) drawing specific attention to BCL-2 inhibition by venetoclax which, in combination with obinutuzumab, conveys an ORR of 100% and a 90% CR in untreated CLL. Prof. Hallek was keen to highlight conflicting trial data in the front line setting. For example, the German CLL Study Group (GCLLSG) trials in the 1990s found the best front-line treatment to be rituximab and bendamustine, or fludarabine, cyclophosphamide and rituximab (FCR), yet a more recent trial (ECOG-ACRIN, summary of the data presented at the 60th Annual Meeting of the American Society of Hematology (ASH) can be found here
) found ibrutinib and rituximab to be more efficacious than rituximab and bendamustine.
The Alliance North American Intergroup Study (AO41202) did not find ibrutinib and rituximab to be better than rituximab and bendamustine. Prof. Hallek went on to present recent results from the CLL14 trials by the GCLLSG. In this study older or unfit patients benefited more from a chemotherapy-free treatment with obinutuzumab and venetoclax in terms of PFS than from chlorambucil and obinutuzumab (a summary of two abstracts presented at the 24th European Hematology Society (EHA) meeting and the 15-ICML are summarised here). In his concluding remarks, Prof. Hallek presented his recommendations regarding front-line CLL treatments:
- Patients with del(17p) or p53 mutations should receive ibrutinib with rituximab or venetoclax combined with obinutuzumab or idelalisib;
- Fit patients with or without IGVH mutation should be treated with FCR or ibrutinib, while bendamustine combined with rituximab whould be used for patients over 65
- Unfit patients with or without an IVGH mutation should receive venetoclax with obinutuzumab or chlorambucil combined with obinutuzumab or ibrutinib.
He went on to advocate caution when using triplet combinations due to the higher risk of side effects.