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Acalabrutinib Improves PFS and OS Over Other First-Line Regimens in CLL

February 17, 2021

Acalabrutinib demonstrated favorable progression free survival (PFS) and overall survival (OS) compared with standard first-line treatments for chronic lymphocytic leukemia (CLL), according to results from a systematic review and network meta-analysis (Clin Ther. 2020;42[10]:1955-1974.e15. doi:10.1016/j.clinthera.2020.08.017).

“Although the ELEVATE-TN trial provided robust evidence regarding the efficacy of acalabrutinib relative to chlorambucil plus obinutuzumab, comparisons with other standard frontline treatment regimens are necessary,” explained the study authors.

This systematic literature review and network meta-analysis compared acalabrutinib with other standard frontline therapies for CLL fludarabine-ineligible patients. Comparators included alemtuzumab, ibrutinib, ibrutinib plus obinutuzumab, ibrutinib plus rituximab, chlorambucil plus rituximab, chlorambucil plus ofatumumab, chlorambucil plus obinutuzumab, bendamustine plus rituximab, and venetoclax plus obinutuzumab.

Two networks were constructed, Network A and Network B. Network A was composed of randomized clinical trials that met inclusion criteria and Network B was composed of 7 randomized clinical trials and a published cross-trial comparison of ibrutinib from RESONATE-2 and chlorambucil plus obinutuzumab from iLLUMINATE.

Bayesian network meta-analyses were conducted PFS and OS.

Significant improvements in PFS for acalabrutinib plus obinutuzumab and acalabrutinib monotherapy over most comparators were shown in both networks. In Network A, a significant difference of PFS for acalabrutinib monotherapy over ibrutinib monotherapy was found. In Network B, a significant difference in PFS for acalabrutinib monotherapy versus venetoclax plus obinutuzumab was found.

SUCRA values were 98% and 100% for acalabrutinib plus obinutuzumab for PFS improvement and 92% and 94% for OS improvement. SUCRA values for PFS were 88% and 90% and OS values 83% and 87 for acalabrutinib monotherapy in Networks A and B, respectively.

“Acalabrutinib, as monotherapy and in combination with obinutuzumab, showed favorable PFS and OS compared with frontline therapies of CLL in fludarabine-ineligible patients,” concluded the study authors.

The authors noted that head-to-head clinical trials are required to confirm the results.—Lisa Kuhns

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