Farrukh Awan, MD, discusses the results of the phase 3 ELEVATE-TN trial of acalabrutinib in patients with chronic lymphocytic leukemia.
Farrukh Awan, MD, associate professor in the department of internal medicine at UT Southwestern Medical Center, discusses the results of the phase 3 ELEVATE-TN trial (NCT02475681) of acalabrutinib (Calquence) in patients with chronic lymphocytic leukemia (CLL).
The population of 535 patients in the trial were randomized 1:1:1 to receive acalabrutinib alone, acalabrutinib plus obinutuzumab (Gazyva), or obinutuzumab plus chlorambucil in 28-day cycles. At a median follow-up of 46.9 months, median progression-free survival (PFS) was not reached for either experimental arm versus 27.8 months with obinutuzumab/chlorambucil, and the investigators observed a 48-month PFS rate of 87.0% for acalabrutinib/obinutuzumab, 77.9% with acalabrutinib alone, and 25.1% for obinutuzumab/chlorambucil.
Awan says the superior efficacy of the acalabrutinib/obinutuzumab combination stood out, though the study was not designed to compare between the acalabrutinib monotherapy and combination. While this may offer better outcomes for some patients, the immunosuppressive toxicity of obinutuzumab could increase risks to patients due to concerns related to COVID-19.
Investigators did not observe any unexpected adverse events (AEs) in the trial. At 4-year follow-up, 74.9% of patients on the acalabrutinib/obinutuzumab arm and 69.3% of the acalabrutinib monotherapy arm remained on treatment.
0:08 | So the ELEVATE-TN study is an important study. It was designed to evaluate the benefit of acalabrutinib over traditional treatments that we would have used in that particular patient population. [The] bottom line is that acalabrutinib, either as a single agent or in combination, was better as compared to the competitor arm of obinutuzumab and chlorambucil, which is not unexpected, because we have had preliminary evidence of the efficacy of acalabrutinib.
I think 1 thing that was interesting was that the outcomes of the group with obinutuzumab in combination with acalabrutinib appear to be the best, although the study was not designed, necessarily, to evaluate that difference between single agent versus dual therapy with acalabrutinib. I feel that that was an important message and point to be considered for certain patients. Now with the COVID pandemic, that complicates the decision-making a little bit.
1:12 | But the fact is that the acalabrutinib had excellent tolerability, expected [AEs] that we have seen; there were no new or unexpected signals from that particular trial with regards to the safety of the drug, and the efficacy continues to be very promising. Four years out, we have more than 75% of patients with excellent disease control, even higher if you were on the combination arm. So I feel that that's a great option for our patients and potentially a less toxic option as compared to other treatments that we've had in the past.