First-Line Targeted Treatment Approach Appears Efficacious for Older CLL Population

Patients 80 years or older with chronic lymphocytic leukemia who received treatment with a targeted therapy experienced benefit regardless of the presence of coexisting conditions and organ dysfunction, according to data from a pooled analysis presented at the 2021 American Society of Hematology Annual Meeting.1

Of the 33 patients included in the study who underwent treatment with a targeted agent, 18.2% had a missing response, 36.4% had a complete response (CR)/CR with incomplete hematologic recovery, and 36.4% had a partial response. The overall response rate was 72.7%. Additionally, investigators noted that treatment outcomes were worse for the geriatric patient population when compared with younger patients.

Multiple trials were utilized for this analysis, including the phase 3 CLL14 study (NCT02242942)2 with venetoclax (Venclexta) plus obinutuzumab (Gazyva), the phase 2 CLL2-GIVe study (NCT02758665)3 with venetoclax, obinutuzumab and ibrutinib (Imbruvica), and CLL2-BXX-Studies (NCT02345863, NCT02401503, NCT02445131, and NCT02689141)4 with optional bendamustine (Bendeka) debulking and either ibrutinib plus obinutuzumab and venetoclax (BIG);or obinutuzumab, ibrutinib, and ofatumumab (Kesimpta; BAG); or idelalisib (Zydelig) and obinutuzumab (BCG). All studies included a population of patients with CLL.

A total of 716 patients were randomized on these studies, among whom 33 were aged 80 years or older and had received at least 1 dose of a targeted agent. Additionally, 324 patients were younger than 80 years and received treatment with targeted therapy. In the geriatric population, 82% of patients were treated with GVe, 3 with BIG, 2 with GIVe, and 1 with BIO.

In terms of patient characteristics, patients had a median age of 82.0 years and over half (54.5%) were male. Additionally, 93.9% of patients had an ECOG performance status between 0 to 1. A total of 9.1% of patients were Binet stage A, 30.3% were stage B, and 60.6% were stage C. Cumulative illness rating scale scores of 6 or less was observed in 29.0% patients, 71.0% had a rating of more than 6, and 6.1% had missing information. Creatinine clearance of less than 70 or found in 90.9% of patients, and 9.1% had a clearance of 70 or higher. Genetic aberrations were observed in the population, the most prominent being in del(13q) alone (36.4%). Moreover, in terms of IGHV mutational status, 56.3% of patients were unmutated, 43.7% were mutated, and 3.0% had missing information. Lastly, 58.6% of patients were deemed high-risk, 31.0% were intermediate, and 10.3% were very high-risk .

Patients who were 80 years or older had a median progression-free survival (PFS) of 49 months, compared with patients who were younger than 80 years for whom the median PFS was not reached. A 4-year overall survival (OS) rate of 68% was observed among patients 80 years or older compared with 92% among those younger than 80 years.

A total of 16 patients discontinued treatment early. Reasons for discontinuation included patients wishing to discontinue (25.0%), progressive disease (18.8%), death (43.8%), and other causes (12.5%).

Overall, 11 documented deaths were reported. One patient each died due to progressive disease, infection, respiratory insufficiency, cardiac arrest, cardiac failure, or unknown cause. In total, 45.5% of patients died from adverse effects, 40% of which were related to treatment, and 60% were unrelated.

References

1. Simon F, Giza A, Robrecht S, et al. Pooled analysis of first-line treatment with targeted agents in patients with chronic lymphocytic leukemia (CLL) aged 80 years and older. Blood. 2021;138(suppl 1):1552. doi:10.1182/blood-2021-150698

2. Fischer K, Al-Sawaf O, Bahlo J, et al. Venetoclax and obinutuzumab in patients with CLL and coexisting conditions. N Engl J Med. 2019;380(23):2225-2236. doi:10.1056/NEJMoa1815281

3. Huber H, Edenhofer S, von Tresckow J, et al. Phase 2 study of obinutuzumab (GA-101), ibrutinib and venetoclax (CLL2-GIVe) in patients with untreated high-risk chronic lymphocytic leukemia. Blood. 2021;138(issue 24). doi:10.1182/blood.2021013208

4. Cramer P, von Tresckow J, Bahlo J, et al. CLL2-BXX Phase II trials: sequential, targeted treatment for eradication of minimal residual disease in chronic lymphocytic leukemia. Future Oncol. 2018;14(6):499-513. doi:10.2217/fon-2017-0442