Amid the wide-ranging research on hematologic cancers reported at the European Hematology Association (EHA) 2023 Hybrid Congress in Frankfurt, Germany, multiple studies focused on recent developments in chronic lymphocytic leukemia (CLL).
Othman Al-Sawaf, MD, of the University Hospital of Cologne in Cologne, Germany, presented the latest findings from ongoing research investigating the long-term efficacy and safety of 1-year fixed-duration venetoclax-obinutuzumab (Ven-Obi) in patients with previously untreated CLL.1
In the open-label, multicenter, randomized, phase 3 CLL14 trial (ClinicalTrials.gov identifier: NCT02242942), the results of which were published in 2019, 432 patients were randomly assigned to receive either 12 cycles of venetoclax and 6 cycles of obinutuzumab or 12 cycles of chlorambucil and 6 cycles of obinutuzumab (Clb-Obi). At 24 months, the Ven-Obi group demonstrated a significantly higher rate of progression-free survival (PFS) compared with the Clb-Obi group (88.2% [95% CI, 83.7-92.6] vs 64.1% [95% CI, 57.4-70.8)].2 These initial results established Ven-Obi as the standard-of-care treatment in previously untreated CLL. It has now been at least 5 years since the CLL14 participants completed the study treatment.1
In his EHA presentation, Dr Al-Sawaf discussed the 6-year results from the ongoing follow-up of the CLL14 study participants. “The aim of these long-term observations that we try to do every year is not so much to do the comparisons to [Clb-Obi], which we appreciate is not necessarily a standard of care anymore, but … to understand how … effective [Ven-Obi] is in the long run,” Dr Al-Sawaf stated in the session.3
According to the updated results, PFS remained superior in the Ven-Obi group compared with the Clb-Obi group, with a median PFS of 76.2 months vs 36.4 months, respectively (hazard ratio [HR], 0.40; 95% CI, 0.31-0.52; P <.0001), after a median follow-up period of 76.4 months (interquartile range 52.5-80.5). The continued benefit in PFS was observed in patients from all risk groups, including those with TP53 mutation/deletion (median PFS, 51.9 months vs 20.8 months, respectively) and unmutated immunoglobulin heavy chain variable region (IGHV) status (median PFS, 64.8 months vs 26.9 months, respectively).1
The estimated investigator-assessed PFS rate (the primary endpoint in the trial) was 53.1% with Ven-Obi and 21.7% with Clb-Obi. Progressive disease was observed in 67 Ven-Obi patients, with 39 cases of second-line therapy initiation, compared with 141 Clb-Obi patients, with 103 second-line therapies. Bruton’s tyrosine kinase (BTK) inhibitors represented the most common second-line therapy used in both arms (61.5% in Ven-Obi patients vs 55.4% in Clb-Obi patients). The cumulative incidence of second primary malignancies was 14.2% in the Ven-Obi group and 8.5% in the Clb-Obi group (P =.071). Richter transformations occurred in 2 and 4 patients in the two arms, respectively. The updated analyses revealed no new safety signals.1
Table 1 details the CLL14 study design (see the Supplementary Appendix for complete inclusion and exclusion criteria),2 and Table 2 explains the secondary outcomes and other results of Ven-Obi vs Clb-Obi.1
Clinical Applicability
In findings presented at the EHA 2023 Hybrid Congress, Dr Al-Sawaf reported the 6-year follow-up data from the CLL14 trial. Results demonstrated the ongoing efficacy of the 1-year fixed-duration Ven-Obi regimen compared with Clb-Obi in patients with CLL who have coexisting conditions. More than one-half of patients showed continued remission 5 years post-treatment, and second-line treatment was not required in more than 60% of patients during that time.1 Based on the CLL14 trial design, follow-up will continue for a total of up to 9 years. “The study is still open, and there will be a further data lock at the end of this year [or] early next year, so we will hopefully be able to substantiate these observations further,” Dr Al-Sawaf concluded.3
Disclosures
The CLL14 trial is sponsored by F. Hoffmann-La Roche, Ltd, and AbbVie, Inc.
References
1. Al-Sawaf O, Robrecht S, Zhang C, et al. Venetoclax-obinutuzumab for previously untreated chronic lymphocytic leukemia: 6-year results of the randomized CLL14 study. Abstract S145 presented at: European Hematology Association (EHA) 2023 Hybrid Congress; June 8-11, 2023; Frankfurt, Germany.
2. Fischer K, Al-Sawaf O, Bahlo J, et al. Venetoclax and obinutuzumab in patients with CLL and coexisting conditions. N Engl J Med. 2019;380(23):2225-2236. doi:10.1056/NEJMoa1815281
3. Al-Sawaf, O. Venetoclax-obinutuzumab for previously untreated chronic lymphocytic leukemia: 6-year results of the randomized CLL14 study. Oral presentation at: European Hematology Association (EHA) 2023 Hybrid Congress; June 9, 2023; Frankfurt, Germany.
Posted by Haymarket’s Clinical Content Hub. The editorial staff of Cancer Therapy Advisor had no role in this content’s preparation.
Reviewed July 2023
