What is chronic lymphocytic leukemia (CLL)?

Chronic lymphocytic leukemia (CLL) is a type of cancer that affects the blood and bone marrow.It is characterized by the slow increase of abnormal lymphocytes, a type of white blood cell.

How effective is venetoclax for treating CLL in elderly patients?

A study published in *Blood Advances* found that venetoclax showed a 91% overall response rate in octogenarians with CLL, wich is comparable to the response rates seen in younger patients.

What are the common side effects of venetoclax treatment?

Common side effects of venetoclax include neutropenia (low white blood cell count) and an increased risk of infections. The study reported a 37% incidence of neutropenia and a 22% incidence of grade 3 or higher infections.

What is the median age of diagnosis for CLL?

The median age of a newly diagnosed patient with CLL is 70 years old, according to the National Institutes of Health .

How does venetoclax compare to BTK inhibitors for treating CLL in older adults?

The study found that venetoclax and Bruton tyrosine kinase inhibitors (BTKis) had comparable overall efficacy, although venetoclax showed a higher rate of complete responses. Venetoclax had fewer cardiovascular toxicities but a higher rate of infectious events compared to BTKIs.

what challenges are associated with venetoclax treatment in elderly CLL patients?

Challenges include the need for extended ramp-up times, reaching the full 400-mg dose, and temporary treatment interruptions. The study found that 32% of patients needed more than 5 weeks for ramp-up, and 43% required temporary interruptions of at least 7 days.

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Indianapolis, IN – august 4, 2025 – Eli Lilly and Company announced today positive topline results from the Phase 3 BRUIN CLL-314 trial, demonstrating that pirtobrutinib (Jaypirca) significantly improved progression-free survival (PFS) compared to ibrutinib (imbruvica) in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). This marks the second accomplished Phase 3 trial for the non-covalent bruton’s tyrosine kinase (BTK) inhibitor, bolstering its potential as a treatment option for heavily pretreated patients.

Pirtobrutinib is indicated for adult patients with mantle cell lymphoma (MCL) who have received at least two prior lines of systemic therapy, including a BTK inhibitor, and for adults with CLL or SLL who have had at least two prior lines of therapy, including both a BTK inhibitor and a BCL-2 inhibitor. The BRUIN CLL-314 trial specifically focused on patients who had progressed after treatment with ibrutinib,a first-generation covalent BTK inhibitor.

These findings build upon the results of the previously published Phase 3 BRUIN-321 trial, detailed in the Journal of Clinical Oncology in June 2025. That study, led by researchers including Dr. John P. Sharman at the University of Washington Medical Center in Seattle, WA, compared pirtobrutinib to investigator’s choice of idelalisib/rituximab or bendamustine/rituximab in patients relapsed or refractory to a covalent BTK inhibitor. The BRUIN-321 trial showed a median PFS of 14 months (95% CI, 11.2-16.6) for pirtobrutinib versus 8.7 months (95% CI, 8.1-10.4) for the control arm. Moreover, patients receiving pirtobrutinib experienced fewer grade 3 or higher treatment-emergent adverse events and a lower rate of treatment discontinuation due to adverse events.

Pirtobrutinib distinguishes itself from earlier BTK inhibitors like ibrutinib thru its non-covalent binding mechanism. This allows it to inhibit BTK more effectively, even in the presence of mutations that can confer resistance to covalent inhibitors. BTK is a crucial signaling molecule in B cells, and its inhibition disrupts the survival and proliferation of malignant cells in CLL and MCL.

According to eli Lilly, the safety profile observed in BRUIN CLL-314 was consistent with previous clinical trials. Detailed data from the trial will be presented at an upcoming medical conference later this year.

“These data mark the second positive phase 3 study in the programme, as we continue to build evidence supporting the potential role of pirtobrutinib in treating people with CLL/SLL and hopefully enabling future regulatory approvals that allow physicians to use the medicine in various disease settings, whether treatment-naive or BTK inhibitor-pretreated,” stated Dr. Maura van Naarden, a Lilly executive.

References

1. Lilly’s Jaypirca (pirtobrutinib), the first and only approved non-covalent (reversible) BTK inhibitor, met its primary endpoint in a head-to-head Phase 3 trial versus Imbruvica (ibrutinib) in CLL/SLL. News release. Eli Lilly. July 29, 2025. Accessed August 4, 2025. https://investor.lilly.com/news-releases/news-release-details/lillys-jaypirca-pirtobrutinib-first-and-only-approved-non

2. Sharman JP, Munir T, Grosicki S, et al. Phase III Trial of pirtobrutinib versus idelalisib/rituximab or bendamustine/rituximab in covalent Brut

August 8, 2025 0 comments

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Venetoclax Shows Promise for Elderly CLL Patients, Study Reveals

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Venetoclax Shows Promise for Elderly CLL Patients, Study Reveals

A recent study published in *blood Advances* highlights the effectiveness of venetoclax (Venclexta) in treating chronic lymphocytic leukemia (CLL) among elderly patients, specifically those over 80. While the drug demonstrates a high response rate, clinicians should be prepared for potential treatment management challenges, including temporary interruptions (CLL).

High Response Rate with Venetoclax in Octogenarians

The retrospective study, conducted across 23 Italian medical centers between 2014 and 2023, involved 120 patients over the age of 80. The findings revealed a 91% overall response rate in this age group, which is comparable to results seen in younger CLL patients. This suggests that venetoclax can be a viable treatment option even for the oldest patients battling CLL.

Did You Know? The median age at diagnosis for CLL is 70 years old, and over a quarter of patients are between 75 and 84 years old when diagnosed national Institutes of Health.

Study Details and Patient Characteristics

The study population had a median age of 81 years at the start of venetoclax therapy. A significant portion of the patients had existing health issues, with 54% having Cumulative Illness Rating Scale scores above 6. Additionally, 53% had impaired kidney function, and a substantial number where at intermediate or high risk of tumor lysis syndrome. Most patients (83%) had relapsed or refractory disease, having undergone a median of two prior lines of therapy.

Treatment Regimens

The patients received venetoclax either as a monotherapy (50%), in combination with rituximab (45 patients), or in combination with obinutuzumab (17 patients).

Efficacy and Safety Profile

The study indicated that venetoclax showed “remarkable efficacy” in the elderly patient group, with a complete response rate of 44% and a progression-free survival of 44 months. Though, the researchers also noted common side effects, including neutropenia (37%) and grade 3 or higher infections (22%).

Pro Tip: Careful patient management is crucial when administering venetoclax to elderly patients. Clinicians should be prepared for potential dose adjustments and temporary treatment interruptions.

Management Challenges and Dose Adjustments

The study highlighted the importance of patient management during venetoclax treatment. Approximately 32% of patients required a ramp-up time exceeding five weeks, and only 78% eventually reached the full 400-mg dose. Furthermore, 43% of patients needed temporary treatment interruptions lasting at least seven days.

Comparison with BTK Inhibitors

Researchers compared the venetoclax findings with data from a similar group of patients treated with Bruton tyrosine kinase inhibitors (BTKis). While both treatments showed comparable overall efficacy,venetoclax had a higher rate of complete responses. The safety profiles differed,with BTKis showing higher rates of cardiovascular toxicities (26% vs. 4%) and venetoclax showing higher rates of infectious events (82% vs. 49%). However,rates of grade 3 and 4 infections were similar between the two groups.

Comparison of Venetoclax and BTK Inhibitors in elderly CLL Patients
Treatment	Overall Response Rate	Complete Response Rate	Cardiovascular Toxicities	Infectious Events
Venetoclax	91%	44%	4%	82%
BTK Inhibitors	Comparable	Lower	26%	49%

It’s vital to interpret these comparisons cautiously due to differences in patient characteristics, such as a higher proportion of patients with

CLL

Pirtobrutinib Shows Promise as Alternative to Ibrutinib in CLL/SLL Treatment

Venetoclax Shows Promise for Elderly CLL Patients – New Study