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

A pooled analysis indicated that patients who were 80 years or older had efficacious responses to targeted therapies for chronic lymphocytic leukemia regardless of coexisting conditions and organ dysfunction.

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