Pooled knowledge affirm that earlier use of Bruton tyrosine kinase (BTK) inhibitors like acalabrutinib (Calquence) could also be extra useful in sufferers with power lymphocytic leukemia (CLL) in contrast with later strains of remedy, in response to Paolo Ghia, MD, PhD.
CancerNetwork® spoke with Ghia, a professor in medical oncology and director of the Strategic Analysis Program on CLL at Università Vita-Salute San Raffaele College in Milan, Italy, concerning the medical implications of information from a pooled evaluation examine assessing the usage of acalabrutinib throughout totally different strains of remedy in CLL.
Ghia famous that the affect of the first-generation BTK inhibitor ibrutinib (Imbruvica) was a lot larger when given within the frontline setting than over subsequent strains in prior research. Investigators subsequently assessed whether or not this heightened efficacy within the front-line setting was constant when utilizing acalabrutinib. The pooled evaluation of the second-generation BTK inhibitor included findings from the ELEVATE-TN examine (NCT02475681), ELEVATE-RR examine (NCT02477696), and ASCEND examine (NCT02970318).
Combining outcomes from the three research confirmed decreased loss of life, illness development, and time to subsequent remedy with frontline remedy in contrast with later strains of remedy. Ghia concluded by highlighting extra extended responses in earlier-line medication.
Ghia offered these findings on the 2024 European Hematology Affiliation (EHA) Congress.
Transcript:
We have been planning to know if the advantage of acalabrutinib, the second-generation BTK inhibitor, would differ relying on the road of remedy. We already had previous proof that affect of ibrutinib, the first-generation BTK [inhibitor], can be a lot larger if sufferers have been handled within the entrance line or in a second line slightly than in subsequent strains.
That’s what we carried out with acalabrutinib utilizing quite a few research the place acalabrutinib was used as [a] monotherapy. We [assessed] sufferers in ELEVATE-TN [who were] remedy naive, the place acalabrutinib was given to aged sufferers alone or together with obinutuzumab [Gazyva] in contrast [with] chlorambucil plus obinutuzumab. Then [we looked at] knowledge within the relapsed/refractory setting from the ELEVATE-RR trial the place sufferers have been handled both with acalabrutinib or ibrutinib. Solely sufferers with 17p deletions and/or 11q deletions [were included]. Then, a 3rd examine, which was the ASCEND examine [included] all comers [with] relapsed/refractory [disease who were treated with] acalabrutinib or doctor’s selection of bendamustine plus rituximab [Rituxan] or idelalisib [Zydelig] plus rituximab.
What we’ve proven right here is that by combining all these sufferers, we do see a decreased threat of loss of life, development, and time to subsequent remedy in sufferers who have been handled with acalabrutinib within the frontline [setting] in contrast [with] these handled in later strains. If we take a look at the sufferers handled within the second line, they nonetheless had a bonus in contrast [with] the sufferers handled in subsequent strains. That was additionally true for sufferers with deletion 17p or TP53 mutations, suggesting, as we all know, that the sooner we use acalabrutinib or BTK inhibitors normally, the higher it’s for the affected person. Within the earlier line, medication can at all times be simpler in having extra extended response.
Reference
Ghia P, John E, Stewart Ok, Scalera A, Byrd JC. Impression of acalabrutinib remedy by line of remedy in sufferers with power lymphocytic leukemia: pooled evaluation from ELEVATE-TN, ELEVATE-RR, and ASCEND. Poster offered at European Hematologic Affiliation 2024 Hybrid Congress; June 13-16, 2024; Madrid, Spain. Summary P703.
