Matthew S. Davids, MD, Discusses Important Abstracts Presented at ASH 2021

There were several very impactful abstracts at this year’s ASH meeting in CLL. One of the more exciting ones that I saw was the CLL13 abstract.¹ This is an almost 1000-patient study going on in Europe which is largely comparing various venetoclax [Vencelxta]–based combinations to chemoimmunotherapy. At this ASH meeting, we saw for the first time the MRD [minimal residual disease] data from the study. Some of the takeaways for me were that the venetoclax plus obinutuzumab [Gazyva] combination performed very well. [There were] high rates of undetectable MRD, certainly much higher than chemoimmunotherapy. [This] wasn’t a huge surprise, but much higher also then venetoclax with rituximab [Rituxan] which is a bit surprising [given] that the CD20 antibody made such a big difference. The study also had a triplet regimen of ibrutinib [Imbruvica], venetoclax, and obinutuzumab, which although looked a bit more potent than venetoclax abilities and on its own. I do think that the doublet performed quite well. It’s an open question whether the third drug is needed in the upfront setting.

We also saw data from SEQUOIA study [NCT03336333] cohort 1 for the first time.² This is a registrational study looking at zanubrutinib [Brukinsa], a newer, more specific BTK [Bruton tyrosine kinase] inhibitor compared with bendamustine and rituximab. This was a positive study favoring the PFS [progression-free survival] with zanubrutinib and is likely to lead to a label for zanubrutinib hopefully in the near future for CLL.

Several other impactful studies were presented in various combinations of ibrutinib [and] venetoclax, both in older patients—for example, in an update to the GLOW study [NCT03462719]³—as well as in younger fit patients in an update to the CAPTIVATE study [NCT02910583]⁴; both really showing very nice, durable responses. We presented some of our data on the combination of ibrutinib plus FCR [fludarabine, cyclophosphamide, rituximab] for younger patients with CLL. This also has proven to be quite durable in terms of deep responses, with a 97% progression-free survival rate with about 40 months of follow-up. [This is] not something that would be broadly applied to a large population of patients with CLL, but particularly for those very young, fit patients who might want the potential for a functional cure of their disease. We think that this is the type of regimen that should be explored in larger comparative studies.

References

1. Eichhorst B, Niemann C, Kater A, et al. A randomized phase III study of venetoclax-based time-limited combination treatments (RVe, GVe, GIVe) vs standard chemoimmunotherapy (CIT: FCR/BR) in frontline chronic lymphocytic leukemia (CLL) of fit patients: First co-primary endpoint analysis of the international intergroup GAIA (CLL13) trial. Presented at the 2021 American Society of Hematology Annual Conference. December 11-14, 2021. Abstract 71. https://bit.ly/3ej0HRx

2. Tam CS, Giannopoulos K, Jurczak W, et al. SEQUOIA: results of a phase 3 randomized study of zanubrutinib versus bendamustine + rituximab (BR) in patients with treatment-naïve (TN) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Presented at the 2021 American Society of Hematology Annual Conference. December 11-14, 2021. Abstract 396. https://bit.ly/3sKdPI7

3. Munir T, Moreno C, Owen C, et al. First prospective data on minimal residual disease (MRD) outcomes after fixed-duration ibrutinib plus venetoclax (Ibr+Ven)versus chlorambucil plus obinutuzumab (Clb+O) for first-line treatment) of CLL in elderly or unfit patients: the Glow study. Presented at 2021 ASH Annual Meeting & Exposition; December 11-13, 2021; Atlanta, GA. https://bit.ly/3plnHph

4. Ghia P, Allan JN, Siddiqi T, et al. First-line treatment with ibrutinib (Ibr) plus venetoclax (Ven) for chronic lymphocytic leukemia (CLL): 2-year post-randomization disease-free survival (DFS) results from the minimal residual disease (MRD) cohort of the phase 2 Captivate study. Presented at 2021 ASH Annual Meeting & Exposition; December 11-13, 2021; Atlanta, GA. Abstract 68. https://bit.ly/3yUPSib