Mazyar Shadman, MD, MPH, on Chronic Lymphocytic Leukemia: Recruiting for the CELESTIAL-TNCLL Study
2024 ASCO Annual Meeting
Mazyar Shadman, MD, MPH, of Fred Hutchinson Cancer Center, discusses an ongoing phase III study of the BCL2 inhibitor sonrotoclax plus zanubrutinib vs venetoclax and obinutuzumab for patients with treatment-naive chronic lymphocytic leukemia. The investigators are recruiting internationally (see NCT06073821; Abstract TPS7087).
Transcript
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
This year at the ASCO meeting, I had the opportunity of presenting a trial in progress. This is CELESTRIAL-CLLTN trial, which is a global head-to-head Phase III trial comparing the investigational combination using zanubrutinib, a second generation BTK inhibitor, in combination with sonrotoclax, which is a novel BCL2 inhibitor, and we are comparing that to a standard arm of venetoclax plus obinutuzumab for treatment of first line CLL patients who require treatment.
As a background, we currently have two options for first line treatment of CLL. We either go with continuous BTK inhibitor therapy until progression or intolerance, or we use a time-limited approach using venetoclax in combination with obinutuzumab. If the study is positive, we'll introduce another time-limited option, which is all oral and chemoimmunotherapy free. Zanubrutinib is already approved for CLL in all lines of therapy, and in clinical trial has been shown to be superior to ibrutinib both from the efficacy and safety standpoint.
Sonrotoclax is a novel BCL2 inhibitor, has shown very promising activity both from the safety and efficacy standpoints. In fact, in a study that was presented at ASH in 2023, we saw an extremely effective combination and also very well-tolerated treatment option for CLL patients.
What this study is trying to do is comparing sonrotoclax and zanubrutinib to venetoclax and obinutuzumab. This is a global study with more than 640 patients planned to be enrolled, and patients will be randomized to receive one of the two options. The primary endpoint is progression-free survival, and we are going for superiority of the investigational arm over the standard of care arm.
This study is currently ongoing, and we encourage our colleagues to contact the participating sites and PIs if they have any patients who requires treatment for first line CLL.
The ASCO Post Staff
Peter Riedell, MD, of The University of Chicago, discusses phase III findings on the regimen of brentuximab vedotin in combination with lenalidomide and rituximab for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). This therapy demonstrated a survival advantage in the third-line setting, but as this is an interim analysis, questions remain regarding long-term safety and duration of response, according to Dr. Riedell (Abstract LBA7005).
The ASCO Post Staff
Sherene Loi, MD, PhD, of Peter MacCallum Cancer Centre, discusses a circulating tumor DNA (ctDNA) analysis from a cohort of patients with early-stage breast cancer who were enrolled in the monarchE trial. This large cohort was studied to look at the usefulness of a personalized tumor-informed assay for ctDNA detection in early stage high-risk patients (LBA507).
The ASCO Post Staff
Toni K. Choueiri, MD, FASCO, of the Dana-Farber Cancer Institute, discusses phase III findings showing that, in patients with advanced renal cell carcinoma (RCC), the benefit of lenvatinib plus pembrolizumab vs sunitinib in overall response rate does not appear to be affected by such factors as gene‐expression signatures for tumor‐induced proliferation, PD‐L1 status, or the mutation status of RCC driver genes.
The ASCO Post Staff
Peter Riedell, MD, of The University of Chicago, discusses phase III results on the use of tucidinostat plus R-CHOP in patients with previously untreated diffuse large B-cell lymphoma (DLBCL) with double expression of MYC and BCL2. The regimen appeared to improve event-free survival and complete response rates vs R-CHOP in the front-line setting. As this is an interim analysis, longer-term follow-up will be needed to better understand its impact, says Dr. Riedell.
The ASCO Post Staff
Luciano J. Costa, MD, PhD, of the University of Alabama at Birmingham, discusses recent findings from the CARTITUDE-4 trial showing that, in patients with lenalidomide-refractory functional high-risk multiple myeloma after one prior line of treatment, ciltacabtagene autoleucel improved outcomes vs the standard of care (Abstract 7504).