Venetoclax Combinations Have Sustained Long-term Benefits for Relapsed, Refractory Chronic Lymphocytic Leukemia

Fixed duration venetoclax (Venclexta/Venclyxto; AbbVie) combination regimens continue to demonstrate long-term efficacy and safety for patients with untreated chronic lymphocytic leukemia (CLL) with co-existing conditions, as well as relapsed or refractory (R/R) CLL, according to updated long-term follow-up data from the phase 3 CLL14 and MURANO studies that will be presented at the European Hematology Association Annual Congress in Frankfurt, Germany.

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"Results from the CLL14 and MURANO studies demonstrate the long-term benefits of fixed-duration venetoclax combinations for patients living with CLL," said Mariana Cota Stirner, MD, PhD, vice president, hematology, AbbVie, in the press release.

Investigators will present findings from a long-term analysis of the phase 3 CLL14 trial. During this study, investigators compared fixed-duration venetoclax plus obinutuzumab (Gazyva; Genentech) with chlorambuci (Leukeran; KG) plus obinutuzumab in previously untreated patients with CLL and co-existing conditions. At the 6-year follow-up:

• Undetectable minimal residual disease (uMRD) was higher with venetoclax combination compared to chlorambucil combination (53% and 21.7%, respectively).
• Time to next treatment (TTNT) was 65.2% with the venetoclax combination compared to 37.1% with the chorambuci combination.
• Progression-free survival (PFS) was higher with the venetoclax combination.
• PFS and TTNT benefits were maintained across risk groups.
• No new safety signals were observed.

The most commonly reported adverse events (AEs) were grade 3 neutropenia, thrombocytopenia, treatment-related infusion-related reaction, anemia, febrile neutropenia, pneumonia, and leukopenia.

"The latest findings show that patients can experience long-term disease control, 5 years after stopping treatment," said CLL14 study investigator Othman Al-Sawaf, MD, a hematologist-oncologist at the University Hospital Cologne in Germany, and study physician at the German CLL Study Group, in the press release.

Investigators will also present findings from a long-term analysis of the phase 3 MURANO trial. During this study, investigators compared fixed-duration venetoclax plus rituximab (Rituxan; Genentech) with bendamustine (Bendeka; Teva) plus rituximab for patients with R/R CLL. At the 7-year follow-up:

• Overall survival (OS) rate was 69.6% with the venetoclax combination compared to 51% with the bendamustine combination.
• 70.3% of patients on the venetoclax combination achieved uMRD upon completing the 2-year treatment cycle.
• Median PFS was 54.7 months with venetoclax and 17 months with bendamustine.
• Patients with uMRD achieved better PFS and OS outcomes than patients with detectable MRD (29%).
• No new safety signals were observed.

The most common AEs associated with the venetoclax-rituximab combination were neutropenia, diarrhea, upper respiratory tract infection, fatigue, and nausea.

"We are pleased to find that uMRD was associated with prolonged PFS in R/R CLL patients after 7 years," said study investigator John Seymour, director of the Integrated Hematology Department at the Peter MacCallum Cancer Center and the Royal Melbourne Hospital in Melbourne, Australia, in the press release.

Venetoclax is a highly selective first-in-class therapeutic that binds to and inhibits the B-cell lymphoma-2 (BCL-2) protein. Targeting BCL-2 can restore the apoptosis of cancer cells. It is being developed by AbbVie and Roche, with US commercialization by AbbVie and Genentech.

Seymour concluded that "these findings continue to support the use of treatment with venetoclax plus rituximab in this patient population."

Reference

AbbVie. AbbVie's VENCLYXTO®/VENCLEXTA® (venetoclax) Continues to Show Sustained Progression-Free Survival (PFS) in Chronic Lymphocytic Leukemia (CLL) Patients. News Release. June 9, 2023. Accessed on June 9, 2023. https://news.abbvie.com/news/press-releases/abbvies-venclyxtovenclexta-venetoclax-continues-to-show-sustained-progression-free-survival-pfs-in-chronic-lymphocytic-leukemia-cll-patients.htm