Skip to Main Content

Advertisement intended for health care professionals

Skip Nav Destination

Venetoclax, Obinutuzumab Improve HRQoL in CLL Despite Existing Geriatric Impairments

August 30, 2023

September 2023

Leah Lawrence

Leah Lawrence is a freelance health writer and editor based in Delaware.

Frontline fixed-duration venetoclax plus obinutuzumab improved patient-reported outcomes and quality of life in older patients with chronic lymphocytic leukemia (CLL), regardless of the presence of geriatric impairments, according to a study published in Blood.

Patients with two or more geriatric impairments at baseline had a lower global health status (p=0.001), physical functioning (p<0.001), and role functioning (p=0.002) and reported significantly more fatigue (p=0.004) and dyspnea (p=0.003) compared with patients with one or no geriatric impairments. However, in general, health-related quality of life (HRQoL) improved over time in all measured subscales regardless of baseline impairments, with greater improvement for role functioning, fatigue, and dyspnea in patients with two or more geriatric impairments.

“For a disease that is incurable like CLL, patient-reported impact on the outcome of the treatment is very important,” said Patrick Connor Johnson, MD, assistant professor of medicine at Harvard Medical School in Boston, who was not involved in the study. “The outcomes we often look at – survival, progression-free survival, physician-reported toxicities – those are critical outcomes, but patient-reported measures are still a critical part of the equation that we need to capture, particularly when discussing therapies that don’t cure the disease.”

The HOVON139/GiVe trial demonstrated that a fixed duration of venetoclax plus obinutuzumab was effective and had an acceptable side-effect profile in patients with previously untreated CLL who were ineligible for fludarabine, cyclophosphamide, and rituximab. Prolonged venetoclax, however, resulted in increased toxicity with only a limited effect on measurable residual disease (MRD).

Mark-David Levin, MD, an internist-​hematologist at the Albert Schweitzer Hospital in the Netherlands, and colleagues with the HOVON CLL study group sought to assess the impact of geriatric assessment on treatment outcomes, HRQoL, and patient-reported outcomes. Led by Lina van der Straten, MD, and Arnon P. Kater, MD, PhD, of Erasmus Medical Center in the Netherlands, the study included 62 patients who were randomly assigned to 12 cycles of venetoclax consolidation (n=32) or MRD-guided venetoclax consolidation (n=30).

Although 96% of patients included in the study had an Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1, more than 90% of patients had one or more geriatric impairments. The median number of geriatric impairments at baseline was two, and 60% of patients had two or more geriatric impairments.

According to Dr. Johnson, this highlights that “ECOG [status] is a limited tool for getting down to the nuances of impairments and is less sensitive than a geriatric assessment instrument.”

Patients who demonstrated two or more geriatric impairments had significantly greater cumulative incidence of grade 3 or worse adverse events (AEs) compared with those with zero to one geriatric impairments (99% vs. 62%; p<0.001). This higher cumulative incidence was the result of a greater rate of non-hematologic AEs.

“There is potential here for the role of geriatric assessment to fine-tune how we think about our patient population when you are administering a targeted therapy in CLL,” said Dr. Johnson. “Clinicians can note something like, ‘This is my higher-risk population for toxicities.’”

Dr. Levin agreed. “It is good to be aware that a subgroup of patients with CLL may benefit less from treatment with venetoclax plus obinutuzumab because of increased risk of toxicity,” he said, noting though that the geriatric parameters and quality of life generally improved in the studied population.

Put another way, the presence of geriatric impairments was not a contraindication to this targeted therapy approach. Additionally, the number of geriatric impairments was significantly reduced after treatment with fixed-duration venetoclax plus obinutuzumab, with patients reporting clinically relevant improvements in HRQoL subscales. Improvements were similar for patients receiving venetoclax consolidation or those who could discontinue treatment due to negative MRD status.

The study was limited by its moderate size, its exclusion of patients with ECOG performance status of 3-4, and its lack of a comparator arm with another modern treatment regimen.

Any conflicts of interest declared by the authors can be found in the original article.

Reference

Van Der Straten L, Stege C, Kersting S, et al. Fixed-duration venetoclax plus obinutuzumab improves quality of life and geriatric impairments in FCR-unfit CLL patients [published online ahead of print, 2023 Jun 26]. Blood. doi: 10.1182/blood.2023020195.

Advertisement intended for health care professionals

Connect with us:

CURRENT ISSUE
November 2024

Advertisement intended for health care professionals

Close Modal

or Create an Account

Close Modal
Close Modal

Advertisement intended for health care professionals