Acalabrutinib Appears More Effective in Earlier Lines of Treatment for CLL


A pooled analysis trial assessed the impact of acalabrutinib in patients with chronic lymphocytic leukemia across treatment lines.

Pooled data affirm that earlier use of Bruton tyrosine kinase (BTK) inhibitors like acalabrutinib (Calquence) may be more beneficial in patients with chronic lymphocytic leukemia (CLL) compared with later lines of therapy, according to Paolo Ghia, MD, PhD.

CancerNetwork® spoke with Ghia, a professor in medical oncology and director of the Strategic Research Program on CLL at Università Vita-Salute San Raffaele University in Milan, Italy, about the clinical implications of data from a pooled analysis study assessing the use of acalabrutinib across different lines of therapy in CLL.

Ghia noted that the impact of the first-generation BTK inhibitor ibrutinib (Imbruvica) was much higher when given in the frontline setting than over subsequent lines in prior studies. Investigators subsequently assessed whether this heightened efficacy in the front-line setting was consistent when using acalabrutinib. The pooled analysis of the second-generation BTK inhibitor included findings from the ELEVATE-TN study (NCT02475681), ELEVATE-RR study (NCT02477696), and ASCEND study (NCT02970318).

Combining results from the 3 studies showed decreased death, disease progression, and time to next treatment with frontline treatment compared with later lines of treatment. Ghia concluded by highlighting more prolonged responses in earlier-line drugs.

Ghia presented these findings at the 2024 European Hematology Association (EHA) Congress.


We were planning to understand if the benefit of acalabrutinib, the second-generation BTK inhibitor, would differ depending on the line of treatment. We already had past evidence that impact of ibrutinib, the first-generation BTK [inhibitor], would be much higher if patients were treated in the front line or in a second line rather than in subsequent lines.

That’s what we carried out with acalabrutinib using a number of studies where acalabrutinib was used as [a] monotherapy. We [assessed] patients in ELEVATE-TN [who were] treatment naive, where acalabrutinib was given to elderly patients alone or in combination with obinutuzumab [Gazyva] compared [with] chlorambucil plus obinutuzumab. Then [we looked at] data in the relapsed/refractory setting from the ELEVATE-RR trial where patients were treated either with acalabrutinib or ibrutinib. Only patients with 17p deletions and/or 11q deletions [were included]. Then, a third study, which was the ASCEND study [included] all comers [with] relapsed/refractory [disease who were treated with] acalabrutinib or physician’s choice of bendamustine plus rituximab [Rituxan] or idelalisib [Zydelig] plus rituximab.

What we have shown here is that by combining all these patients, we do see a decreased risk of death, progression, and time to next treatment in patients who were treated with acalabrutinib in the frontline [setting] compared [with] those treated in later lines. If we look at the patients treated in the second line, they still had an advantage compared [with] the patients treated in subsequent lines. That was also true for patients with deletion 17p or TP53 mutations, suggesting, as we know, that the earlier we use acalabrutinib or BTK inhibitors in general, the better it is for the patient. In the earlier line, drugs can always be more effective in having more prolonged response.


Ghia P, John E, Stewart K, Scalera A, Byrd JC. Impact of acalabrutinib treatment by line of therapy in patients with chronic lymphocytic leukemia: pooled analysis from ELEVATE-TN, ELEVATE-RR, and ASCEND. Poster presented at European Hematologic Association 2024 Hybrid Congress; June 13-16, 2024; Madrid, Spain. Abstract P703.

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