In CLL, early use of acalabrutinib/acalabrutinib is associated with improved survival

Acalabrutinib use in early-line treatments (LOTs) is associated with improvements in overall survival (OS), progression-free survival (PFS) and time to next treatment (TTNT) in patients with chronic lymphocytic leukemia (CLL), according to pooled analysis data published in 2024. A pooled analysis of the Phase 3 ELEVATE-TN (NCT02475681), ELEVATE-RR (NCT02477696), and ASCEND (NCT02970318) trials demonstrated this benefit in the overall patient population and in patients with deletion 17p (del[17p]) who were previously enrolled in smaller cohorts.

Across the overall population, those with no prior batches had better outcomes than those with a prior batch; in the overall population, patients with 1 prior batch also had consistently improved outcomes compared with patients with 2 or more prior batches and patients with del(17p).

The second-generation Bruton kinase inhibitor acotinib previously demonstrated acceptable efficacy and safety compared to ibrutinib (Imbruvica) in patients with relapsed/refractory CLL, with a median of 2 batches in these patients. In the pooled analysis of ibrutinib, patients had better OS and PFS after 0 lines compared with 3 or more prior lines. Researchers in this report evaluated the impact of prior batch numbers of acotinib on the treatment of treatment-naïve or relapsed/refractory CLL, which was previously unknown.

Data from the acotinib monotherapy arm of the Phase 3 trial were also reviewed. The ELEVATE-TN trial had a median follow-up of 74.5 months, with 179 patients receiving 0 prior batches; the ELEVATE-RR trial had a median follow-up of 40.9 months, with 132 patients receiving 1 prior batch and 135 patients receiving 2 or more prior batches; the ASCEND trial had a median follow-up of 46.5 months, with 82 patients receiving 1 prior batch and 73 patients receiving 2 or more prior batches.

Analytical results includeOS, PFS and TTNT, as well as HR and log-rank P values comparing 0 versus 1 prior batch and 1 versus 2 or more prior batches. Across the entire population, patients with 0 prior batches had a 45% lower risk of death than patients with 1 prior batch (P=0.0185); 92% and 85% of patients, respectively, survived 36 months. Patients with 0 prior batches and 1 prior line had a 56% lower risk of disease progression or death (P<0.0001), the risk of initiating subsequent treatment was reduced by 52% (P=0.0001). At 36 months, 84% of patients with prior batch 0 were progression-free and not starting subsequent treatment, compared with 73% and 75% of patients with prior batch 1, respectively.

Patients with 1 prior batch had a 46% lower risk of death than those with 2 or more prior batches (P=0.0016), with 85% of patients with 1 prior batch surviving compared with 76% of patients with 2 or more prior batches at 36 months. Compared with 2 or more prior studies, 1 prior study was associated with a 39% lower risk of disease progression or death (P=0.0012), with 73% of patients being progression-free at 36 months and 58% of patients being progression-free. Among patients with 1 preexisting medical condition, the risk of initiating subsequent therapy was reduced by 33% (P=0.0070), with 75% of patients not initiating subsequent therapy compared with 64% at 36 months.

The increased risk of death in the overall population was associated with previous batches,TP53 mutations, ECOG functional status of 2 or above, Rai stage III or above, age 65 or above, and male sex. Although the analysis of del(17p) patients with previous batches 0 and 1 was not powered due to the small sample size of patients with previous batches 0 and 1, we examined OS, PFS, and TTNT in patients with del(17p) with previous batches 1 and 2 or more.

The findings were consistent in patients with del(17p), in which patients with 1 prior LOT had a significantly lower risk of death (P=0.0072), disease progression or death (P=0.0004), and initiation of subsequent therapy (P=0.0091) compared with patients with 2 or more prior lines of therapy.

At 36 months, 81% and 65% of patients were alive, 74% and 45% were progression-free, and 72% and 56% had not started subsequent treatment. The most common reasons for treatment discontinuation of acotinib monotherapy were adverse events, at 17.9%, 13.1%, and 22.6% in the 0, 1, and 2 or more prior batch groups, respectively, and disease progression at 14.0%, 23.4%, and 31.7%, respectively.