Acalabrutinib, Alone or With Obinutuzumab, Improves Quality-Adjusted Survival in Frontline CLL


Treatment with acalabrutinib as monotherapy or in combination with obinutuzumab improved quality-adjusted survival compared with chlorambucil plus obinutuzumab in patients with treatment-naïve chronic lymphocytic leukemia.

Treatment with acalabrutinib (Calquence) as monotherapy or in combination with obinutuzumab (Gazyva) improved quality-adjusted survival compared with chlorambucil plus obinutuzumab in patients with treatment-naïve chronic lymphocytic leukemia (CLL), according to results presented at the 2021 International Workshop on CLL.1

The findings come from a post-hoc Q-TWiST analysis of patient level data from the randomized, open-label phase ELEVATE-TN trial comparing the 2 treatment regimens, which were presented as a poster by Jeff P. Sharman, MD, director of research from Willamette Valley Cancer Institute and Research Center, and colleagues.

A Q-TWiST (quality-adjusted time without symptoms or toxicity)analysis assesses the balance of risk (toxicity) and benefit (prolonged survival without symptoms of progression or adverse events) of oncologic treatments. Q-TWIST incorporates both the benefits and risks of the drug effect, capturing toxicity and mortality effects of treatment over the follow-up of a clinical trial.

Patients treated with acalabrutinib monotherapy had a significantly longer mean duration of time spent without toxicity (TWiST) compared with those treated with chlorambucil plus obinutuzumab at 24.94 months vs 19.53 months, respectively (P < .0001), while also experiencing a significantly shorter duration of relapse (1.39 vs 5.64 months; P < .0001). The acalabrutinib-monotherapy arm also had a numerically shorter time with toxicity at 1.11 vs 1.65 months with chlorambucil/obinutuzumab (P = .126). Overall, Q-TWiST duration was significantly longer with acalabrutinib monotherapy compared with chlorambucil plus obinutuzumab at 26.20 vs 23.18 months, respectively (P < .0001).

Patients treated with the acalabrutinib-plus-obinutuzumab combination, compared with chlorambucil plus obinutuzumab, had a significantly longer duration of TWiST at 25.10 vs 19.53 months, respectively (P < .0001), a significantly shorter time spent in relapse (0.14 vs 5.64 months; P < .0001), and a significantly longer Q-TWiST duration (26.14 vs 23.18 months; P < .0001), and a numerically longer duration of time spent with toxicity (1.94 vs 1.65 months; P = .4847).

“The relative gain in Q-TWiST is equivalent to 11.3% and 11.0% of OS [overall survival] time in acalabrutinib monotherapy and acalabrutinib plus obinutuzumab, respectively; the gains were considered clinically important as they met the criterion of 10% used to determine clinically important Q-TWiST improvement,” the authors wrote.

Previously in ELEVATE-TN, acalabrutinib/obinutuzumab and acalabrutinib monotherapy significantly improved progression-free survival (PFS) compared with obinutuzumab plus chlorambucil, with tolerable safety in patients with treatment-naive CLL.2

Patients in the study were randomized 1:1:1 to receive oral acalabrutinib (100 mg twice daily continuously) alone or combined with intravenous obinutuzumab (1000 mg on days 1, 2, 8, and 15 of cycle 2, and day 1 of subsequent 28-day cycles for a total of 6 cycles), or obinutuzumab plus oral chlorambucil (0.5 mg/kg on days 1 and 15 of each 28-day cycle for 6 cycles).

At a median follow-up of 28.3 months, the median PFS was not reached with acalabrutinib or acalabrutinib plus obinutuzumab compared with 22.6 months for chlorambucil plus obinutuzumab (HR, 0.1; 95% CI, 0.06-0.17; P < .0001), and a lower or similar incidence of grade 3/4 adverse events.

For the Q-TWiST analysis, the restricted mean duration for each health state was derived from the area under the Kaplan Meier survival curve.

A limitation of the analysis was the use of immature clinical trial data, according to the investigators. “Given the indolent nature of CLL and acalabrutinib as a chronic treatment, maturity of clinical trial data can be achieved in long-term follow-up only; therefore, an updated analysis from ELEVATE-TN with longer term follow-up [median of 47 months] is planned to validate the findings presented herein,” they wrote.


  1. Sharman JP, Emeribe U, Cai L, Gaitonde P. A quality-adjusted survival (Q-TWiST) analysis of acalabrutinib with or without obinutuzumab in patients with treatment-naïve chronic lymphocytic leukemia (CLL). Presented at: 2021 ESMO Congress; September 16-21, 2021; virtual. Abstract 1083755.
  2. Sharman JP, Egyed M, Jurczak W, et al. Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzumab for treatment-naïve chronic lymphocytic leukemia (ELEVATE TN): a randomized, controlled phase 3 trial. Lancet. 2020;395(10232):1278-1291. doi:10.1016/S0140-6736(20)30262-2
Related Videos
Bhagirathbhai Dholaria, MBBS, associate professor, medicine, Division of Hematology and Oncology, Vanderbilt University Medical Center
Pasi A. Jänne, MD, PhD, discusses an exploratory analysis from the FLAURA2 trial of osimertinib plus chemotherapy in treatment-naive, EGFR-mutant NSCLC.
Eric S. Christenson, MD
Jennifer Brown, MD, PhD
Samer A. Srour, MB ChB, MS
Rebecca L. Porter, MD, PhD
Deborah J. Wong, MD, PhD
Michael R. Migden, MD
Saad J. Kenderian, MB, CHB
Eduardo Sotomayor, MD