The results of the Elevate-TN trial, a phase 3 clinical trial evaluating the efficacy of acalabrutinib-containing regimens in patients with chronic lymphocytic leukemia (CLL), have demonstrated promising outcomes. The trial compared the progression-free survival (PFS) rates of acalabrutinib in combination with obinutuzumab against obinutuzumab-chlorambucil treatment. Additionally, the study assessed the impact of acalabrutinib monotherapy. The findings reveal significantly improved PFS rates in patients receiving acalabrutinib-containing regimens, suggesting a potential new standard of care for CLL patients.
Findings: The median investigator-assessed PFS was not reached in the acalabrutinib-containing arms, indicating a substantial benefit over obinutuzumab-chlorambucil, which had a median PFS of 27.8 months (both p < 0.0001). A post hoc analysis demonstrated a prolonged PFS when acalabrutinib was combined with obinutuzumab compared to acalabrutinib monotherapy (p = 0.0296). However, it is important to note that the study was not adequately powered for this particular comparison.
| Treatment Arm | Median PFS (months) | 48-Month PFS Rate (%) |
|---|---|---|
| Acalabrutinib + Obinutuzumab | Not reached | 87.0% |
| Acalabrutinib monotherapy | Not reached | 77.9% |
| Obinutuzumab-Chlorambucil | 27.8 | 25.1% |
Note: PFS = Progression-Free Survival
The efficacy of acalabrutinib-containing regimens remained consistent across high-risk genomic subgroups. Patients with del(17)(p13.1) and/or mutated TP53 experienced a median PFS that was not reached in the acalabrutinib-containing arms, whereas the median PFS for obinutuzumab-chlorambucil was 17.5 months (both p < 0.0001). Similar results were observed in patients with only del(17)(p13.1). In patients with unmutated IGHV, the median PFS was not reached in the acalabrutinib-containing arms, in contrast to 22.2 months for obinutuzumab-chlorambucil (both p < 0.0001). Notably, the median PFS was not reached in any treatment arm for patients with mutated IGHV.
| Genomic Subgroup | Median PFS (months) | 48-Month PFS Rate (%) |
|---|---|---|
| Del(17)(p13.1) and/or mutated TP53 | Not reached | 74.8% (Acalabrutinib + Obinutuzumab) / 76.2% (Acalabrutinib monotherapy) |
| Only Del(17)(p13.1) | Not reached | – |
| Unmutated IGHV | Not reached | 85.7% (Acalabrutinib + Obinutuzumab) / 77.1% (Acalabrutinib monotherapy) |
| Mutated IGHV | Not reached | – |
Furthermore, the estimated 48-month PFS rates were remarkable, highlighting the long-term benefits of acalabrutinib-containing regimens. The overall 48-month PFS rates were 87.0% for acalabrutinib-obinutuzumab, 77.9% for acalabrutinib monotherapy, and 25.1% for obinutuzumab-chlorambucil. Among patients with del(17)(p13.1) and/or mutated TP53, the 48-month PFS rates were 74.8% for acalabrutinib-obinutuzumab and 76.2% for acalabrutinib monotherapy. Patients with unmutated IGHV achieved 48-month PFS rates of 85.7% with acalabrutinib-obinutuzumab and 77.1% with acalabrutinib monotherapy.
Conclusion: The Elevate-TN trial suggests for the superiority of acalabrutinib-containing regimens in terms of progression-free survival for patients with chronic lymphocytic leukemia. The results demonstrate that acalabrutinib, either as monotherapy or in combination with obinutuzumab, offers substantial benefits across high-risk genomic subgroups.
