Acalabrutinib-Based Combination Treatments for CLL

Patients who participated in the ELEVATE-TN study either were aged 65 years or above, or they were under age 65 and had coexisting medical conditions. Their median age was 70 years. Most (81%) had either high-risk or very high-risk chronic lymphocytic leukemia (CLL).

The 535 enrolled patients received either oral acalabrutinib twice daily, acalabrutinib alone (monotherapy), or acalabrutinib combined with intravenous obinutuzumab for 6 cycles; or they received obinutuzumab plus oral chlorambucil for 6 cycles.

Progression-free survival (PFS) of acalabrutinib plus obinutuzumab versus obinutuzumab plus chlorambucil was the primary end point. Key secondary end points included overall response rate, overall survival (OS), and safety. In patients who achieved complete responses with or without complete marrow recovery, minimal residual disease (MRD) status was tested using either blood or bone marrow. Patients who received obinutuzumab plus chlorambucil could switch to acalabrutinib when their disease progressed.

After median follow-up of 28 months, acalabrutinib plus obinutuzumab significantly prolonged PFS compared with obinutuzumab plus chlorambucil. Patients’ risk of progression or death was reduced by 90% with acalabrutinib plus obinutuzumab. Treatment with acalabrutinib alone also extended PFS compared with obinutuzumab plus chlorambucil. The percentages of patients with CLL who were progression-free after 30 months with acalabrutinib plus obinutuzumab, acalabrutinib monotherapy, and obinutuzumab plus chlorambucil were 90%, 82%, and 34%, respectively. PFS improvements with acalabrutinib were seen across patient subgroups, including patients with del(17p).

Median OS has not yet been reached in any of the 3 study arms. In the patients who received acalabrutinib plus obinutuzumab, acalabrutinib monotherapy, or obinutuzumab plus chlorambucil, estimated rates of patient survival at 30 months were 95%, 94%, and 90%, respectively. Five patients (3%) in the acalabrutinib plus obinutuzumab arm, 11 patients (6%) in the acalabrutinib arm, and 55 patients (31%) in the obinutuzumab plus chlorambucil arm have received another therapy. One-quarter (25%) of patients who received obinutuzumab plus chlorambucil crossed over to receive acalabrutinib alone.

Overall response rate (ORR) was higher for acalabrutinib plus obinutuzumab (94%) compared with obinutuzumab plus chlorambucil (79%). ORR for acalabrutinib alone was 85%.

Side effects were similar among the patients who received acalabrutinib. Infusion reactions were less frequent with acalabrutinib plus obinutuzumab (13%) than with obinutuzumab plus chlorambucil (40%). Side effects led to treatment discontinuation in 11% of patients on acalabrutinib plus obinutuzumab, 9% of those taking acalabrutinib alone, and 14% of patients taking obinutuzumab plus chlorambucil. With more than 2 years of follow-up, 79% of patients in both the acalabrutinib-containing groups remain on acalabrutinib.

Researchers concluded that acalabrutinib plus obinutuzumab and acalabrutinib monotherapy significantly extended PFS compared with obinutuzumab plus chlorambucil. The 2 acalabrutinib regimens were also tolerable, making them viable choices for patients with treatment-naïve CLL.

Abstract 31. ASH 2019.