The following article features coverage from the American Society of Hematology 2019 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

In real-world settings, most (nearly 93%) of patients with chronic lymphocytic leukemia (CLL) receive novel-agent therapies — and they receive these most often in the second-line setting, researchers reported in a poster on display during the 61st American Society of Hematology (ASH) Annual Meeting and Exposition in Orlando, Florida.

“The treatment paradigm is evolving with the introduction of novel agents,” reported lead author Anthony R. Mato, MD, MSCE, of the Memorial Sloan Kettering Cancer Center in New York City, in the poster abstract. The findings from Dr Matos and colleagues provided “a baseline description of treatment sequence patterns enabling clinicians to benchmark the impact of the introduction of novel agents and associated outcomes.”

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While novel agents have changed CLL treatment, real-world treatment sequence patterns and outcomes have not been well studied, the authors noted. They therefore sought to describe real-world treatment sequence patterns with novel agents, and treatment sequencing following venetoclax, using data from the CLL Collaborative Study of Real-World Evidence (CORE), a retrospective, multicenter, collaborative observational study of patients with CLL/small lymphocytic leukemia (SLL).

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Data were analyzed for adult patients who initiated therapy for CLL/SLL in the relapsed/refractory setting after February 12, 2014. Treatment sequencing and clinical responses after treatment with BCL-2 inhibitor venetoclax, or novel agents in the B-cell receptor pathway inhibitor (BCRi) class such as ibrutinib, idelalisib, acalabrutinib, or another novel BCRi medication, were assessed. 

Of the 355 patients available at the time of data analysis, 329 patients (93%) received a novel agent in at least 1 line of therapy. In addition, 120 patients (33.8%) received novel agents in 2 or more lines of therapy.

In terms of BCRi medications specifically, 313 patients (88.2%) received these drugs in at least 1 line of therapy; most patients (55.6%) received these BCRi-based therapies in the second line.

The most common BCRi-based therapy used was ibrutinib (85.3%), but 42.8% of these patients ended up needing another line of therapy. The most common subsequent therapy post-BCRi was venetoclax, which was typically administered as a second-line therapy (in 43% of patients who had a follow-up therapy). Venetoclax was used in at least 1 line of therapy in 101 patients (28.5%), and they were most likely to receive this drug in the 3rd-line setting.

Most patients (53%) were first exposed to any novel therapy in the second-line setting. And, 54 patients (15.2%) first received novel therapies in the frontline setting; 59 patients (16.6%) first received them in the third-line; and 28 (7.9%) first got novel agents in the fourth-line or later setting. Finally, 26 patients (7.3%) received no novel therapies, the authors reported.  

In the frontline setting, the most common therapy administered was chemotherapy/chemoimmunotherapy (CT/CIT), in 66.8% of patients. The most common therapy in the second line was a novel agent, given to 63.1% of patients.

Among novel agents, ibrutinib was the most common first novel agent used, in 79.3% of patients. In contrast, venetoclax was used as a first novel agent in only 7.3% of patients. Idelalisib monotherapy was a first novel agent in 18 patients (5.5%); acalabrutinib monotherapy was a first novel agent for 14 (4.3%) patients; other novel therapies (not specifically listed) were first used in 12 (3.6%) of patients.

In patients who received BCRi in any line, 21.4% achieved complete remission; 42.5 achieved partial remission. For those who subsequently progressed after first BCRi, 17.2% later achieved CR; 32.8% achieved a partial response.

Disclosure: AbbVie participated in the study. Some of the authors disclosed financial relationships with the pharmaceutical industry. For a full list of disclosures, please refer to the original abstract.

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Mato AR, Sail K, Yazdy MS, et al. Treatment sequences and outcomes of patients with CLL treated with venetoclax and other novel agents post introduction of novel therapies.Presented at: 61st American Society of Hematology (ASH) Annual Meeting and Exposition; December 7-10, 2019; Orlando, FL. Abstract1756.