In a nutshell
This study aimed to investigate the long-term safety and effectiveness of acalabrutinib (Calquence) with or without obinutuzumab (Gazyva) versus obinutuzumab with chlorambucil (Leukeran) in patients with chronic lymphocytic leukemia (CLL) that have never received treatment (treatment-naive).
This study concluded that the effectiveness of acalabrutinib–obinutuzumab treatment was maintained after 4 years in these patients.
Some background
A first line treatment for CLL involves the immunotherapy obinutuzumab with a chemotherapy drug such as chlorambucil. Obinutuzumab activates the immune system to attack and kill cancer cells.
Targeted therapy drugs such as Bruton tyrosine kinase (BTK) inhibitors have improved outcomes for patients with CLL. These drugs block the protein Bruton tyrosine kinase that helps CLL cells survive and grow. Ibrutinib is one such treatment that worked well in treatment-naïve (TN) patients. However, cardiovascular toxicity is a concern with continuous use.
Acalabrutinib is a next-generation, selective BTK inhibitor approved for CLL/small lymphocytic leukemia (SLL). Acalabrutinib, alone or with obinutuzumab, has shown good effectiveness in clinical trials. However, it was unknown if acalabrutinib with or without obinutuzumab was safe and effective long-term for patients with TN CLL.
Methods & findings
This study involved 535 patients aged 65 and over or 18 to 65 years with other medical conditions who had TN CLL. 179 patients received acalabrutinib–obinutuzumab (AcObi) treatment, 179 received acalabrutinib alone (Ac group) and 177 received obinutuzumab–chlorambucil (ObiCh). Crossover to Ac was permitted in patients who progressed on ObiCh. Patients were followed up for an average of 46.9 months.
74.9% of patients in the AcObi group and in 69.3% of patients in the Ac group were still undergoing treatment at follow-up. 39% of the ObiCh group crossed over to the Ac group.
The average survival without cancer worsening was 27.8 months in the ObiCh group compared to not-reached (was still ongoing at follow-up) in both Ac groups. It was estimated that after 4 years, 87% in the AcObi group were alive without cancer worsening compared to 77.9% in the Ac group, and 25.1% in the ObiCh group.
The average overall survival (OS) was not reached in any treatment arm. After 4 years, it was estimated that 92.9% of the AcObi group were alive compared to 87.6% in the Ac group and 88% in the ObiCh group.
Overall, significantly more patients in the AcObi group responded to treatment (96.1%) compared to the ObiCh group (82.5%). The Ac group had a response rate of 89.9%.
The complete response (CR; complete disappearance of cancer) rate, including CR with incomplete hematologic recovery (CRi), was significantly higher (30.7%) for the AcObi group compared to 13% for the ObiCh group and 11.2% for the Ac group.
The most common side effects were diarrhea, headache, and low white blood cells for AcObi, diarrhea and headache for Ac, and low white blood cells, infusion-related reaction, and nausea for ObiCh. 12.8% of the AcObi group had side effects compared to 12.3% of the Ac group and 14.7% of the ObiCh group.
The bottom line
This study concluded that the safety and effectiveness of AcObi and Ac alone were maintained after 4 years in patients with TN CLL compared to ObiCh.
The fine print
This study was funded by Acerta Pharma, the manufacturer of acalabrutinib.
Published By :
Leukemia
Date :
Jan 01, 2022
