Acalabrutinib treatment in CLL, insights from the ELEVATE-TN study
Dr Sharman presents the 6-year follow-up outcomes of the ELEVATE-TN study, a prospective, randomized phase 3 investigation involving previously untreated patients with CLL. Three cohorts were subjected to distinct treatments: standard chemotherapy with obinutuzumab (O) and chlorambucil, monotherapy with acalabrutinib (A), and the combined regimen of A and O.
The data explore subtle nuances within the study findings. Key findings reveal that patients receiving the combined A+O treatment exhibited a 6-year PFS rate of 78%, whereas those receiving A alone demonstrated a PFS of 62%. Notably, the PFS was substantially lower in the chemo-immunotherapy group, leading to the approval of A monotherapy or its combination in previously untreated patients.
This presentation addresses the question of the added value of including O with A, given the lack of consensus in the field regarding whether the use of an anti-CD20 monoclonal antibody confers additional benefits to A monotherapy.
The study establishes an absolute 16% improvement in PFS with the addition of O. However, as the incorporation of O is not yet widely adopted in the treatment landscape, this study aimed to elucidate this aspect.
Pooling data from both A treatment arms, it was observed that patients achieving CR experienced significantly better PFS, a novel finding that has not been previously demonstrated. Furthermore, individuals receiving O exhibited higher rates of CR, indicating that doublet therapy enhances CR and, consequently, PFS.
Exploring the impact of O addition on various molecular subgroups, it was evident that the presence of uIGHV mutation had no discernible effect on A or A+O treatment. Interestingly, patients with del(17P) did not derive added benefit from the inclusion of O. Therefore, considering these factors could assist physicians in identifying optimal candidates for anti-CD20 antibody therapy.
This prompts the question of the optimal frontline therapy for CLL TN patients. Various treatment options, including BTKi monotherapy, BTKi and anti-CD20 therapy, BCL-2 and CD20, or BTKi and BCL-2 combinations, can be considered. However, a definitive answer remains elusive and awaits further investigations such as the MAGIC study, which aims to shed light on optimal doublet therapy.
References:
Sharman JP. et al. Acalabrutinib ± Obinutuzumab Vs Obinutuzumab + Chlorambucil in Treatment-Naive Chronic Lymphocytic Leukemia: 6-Year Follow-up of Elevate-TN. ASH2023 Oral and Poster Abstracts 636
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