HAEMATOLOGICAL CANCER

Acalabrutinib — a new option in CLL

Patients with chronic lymphocytic leukaemia (CLL) can derive benefit from the BTK inhibitor ibrutinib, alone or in combination with anti-CD20 antibodies (such as rituximab and obinutuzumab). Now, results from the phase III ELEVATE-TN trial indicate that acalabrutinib, another BTK inhibitor, is a new treatment option for these patients.

In ELEVATE-TN, patients with untreated CLL, who were aged ≥65 years, or 18–65 years and with comorbidities, were randomly allocated to receive acalabrutinib, either alone (n = 179) or in combination with obinutuzumab (n = 179), or obinutuzumab plus the cytotoxic agent chlorambucil (n = 177). After a median of 28.3 months, median progression-free survival (PFS) durations were not reached (NR) with acalabrutinib combination and monotherapy, and 22.6 months with chlorambucil combination (HR 0.1, 95% CI 0.06–0.17; P <0.0001 and HR 0.2, 95% CI 0.13–0.30; P <0.0001 for acalabrutinib combination and monotherapy, respectively, versus chlorambucil combination). At 24 months, PFS estimates were 93%, 87% and 43%, respectively. This PFS benefit was consistent across patient subgroups.

Overall response rates were 94%, 86% and 79% with acalabrutinib combination, monotherapy and chlorambucil combination, respectively (P <0.0001 and P <0.08 for acalabrutinib combination and monotherapy, respectively, versus chlorambucil combination). Of these responses, 13%, 1% and 5%, respectively, were complete responses.

The incidence of grade ≥3 adverse events (AEs) was 70.2%, 49.7% and 69.8% in patients receiving acalabrutinib combination, monotherapy and chlorambucil combination, respectively, most commonly neutropenia (30%, 9% and 41%, respectively). AE-related treatment discontinuation occurred in 11%, 9% and 14% of patients, respectively.

“researchers have aimed to determine the best regimen for different subgroups”

In November 2019, the FDA approved acalabrutinib for adults with CLL or small lymphocytic lymphoma (SLL), regardless of age and comorbidities, in a decision partly based on the results from ELEVATE-TN. Several agents are currently approved for patients with CLL, and over the past few years researchers have aimed to determine the best regimen for different subgroups. In the phase III iLLUMINATE trial, involving a patient population similar to that in ELEVATE-TN, median PFS durations were NR and 19.0 months with obinutuzumab plus either ibrutinib or chlorambucil (HR 0.23; P <0.0001); 30-month PFS was 79% versus 31%. Results from trials comparing acalabrutinib versus ibrutinib in patients with CLL are eagerly awaited.

References

Original article

  1. Sharman, J. P. et al. Lancet 395, 1278–1291 (2020)

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  1. Moreno, C. et al. Lancet Oncol. 20, 43–56 (2019)

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Correspondence to Diana Romero.

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Romero, D. Acalabrutinib — a new option in CLL. Nat Rev Clin Oncol 17, 390 (2020). https://doi.org/10.1038/s41571-020-0381-3

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