Jennifer A. Woyach, MD, on New Findings on CLL, COVID-19, and Treatment With Obinutuzumab Plus Venetoclax

2023 ASCO Annual Meeting


Jennifer A. Woyach, MD, of The Ohio State University Comprehensive Cancer Center, discusses results of a phase III study showing that progression-free survival with ibrutinib plus obinutuzumab plus venetoclax is not superior to ibrutinib plus obinutuzumab for treatment-naive older patients with chronic lymphocytic leukemia (CLL) in the setting of the COVID-19 pandemic. Long-term follow-up will determine whether there are advantages to obinutuzumab plus venetoclax, with special attention to measurable residual disease and therapy discontinuation (Abstract 7500).


Disclaimer: This video transcript has not been proofread or edited and may contain errors.
The Alliance A041702 trial is an NCTN phase III clinical trial looking at initial therapy for older patients with previously untreated chronic lymphocytic leukemia, or CLL. The study was investigating the regimen of ibrutinib plus venetoclax plus obinutuzumab compared with the doublet of ibrutinib plus obinutuzumab. The study is actually the successor trial to the A041202 study, which demonstrated a superior progression-free survival for either ibrutinib given alone or in combination with rituximab compared with chemoimmunotherapy with bendamustine plus rituximab. So even though ibrutinib does produce long-term durable remissions for many patients, patients do have trouble sometimes with the indefinite administration of therapy in terms of long-term toxicity and sometimes financial implications of a continuous treatment as well. So the purpose of this study was to see whether adding venetoclax to this doublet might allow more patients to have undetectable minimal residual disease and complete responses and thus be able to discontinue therapy. So the way the trial is designed is patients were randomized to the triplet, again ibrutinib, venetoclax, obinutuzumab, or IVO, or the doublet ibrutinib plus obinutuzumab. After a year of treatment, and this included just six months of the antibody, all patients underwent a response evaluation. Those patients that were on the doublet arm all then continued ibrutinib indefinitely, and the patients on the triplet arm underwent a response-adapted either discontinuation of ibrutinib or continuation of therapy. The reason this study is being presented so early is because it actually did meet its futility boundary, meaning that IVO is not superior to IO. However, importantly, we do think that this study may have been confounded somewhat by the COVID-19 pandemic, where the death rate from COVID-19 was higher in patients treated on the triplet arm than those treated on the doublet arm. Outside of this, the toxicity profile between the two regimens was actually relatively similar. There was a little bit higher a risk of hematologic toxicity with the additional of venetoclax, but non-hematologic toxicity in general was fairly similar on the two arms. So when we look at progression-free survival at this time, which we have about 14 months of follow-up right now, it actually is very similar between the triplet and the doublet with the PFS trending towards favoring the doublet a little bit over the triplet. However, when we censor patients who died of COVID-19, we actually see that trend reversed, where there is a trend towards improved PFS with the triplet versus the doublet. Because of this, we think it's going to be really important to follow this study long-term. Though we are not ever going to be able to conclude that IVO is a better therapy than IO in this patient population, it may be that some patients would benefit from the discontinuation of therapy. And we really will only see that when we have much longer follow-up and many more patients who have actually discontinued the treatment. In addition to long-term follow-up on this study, we are going to continue, in the Alliance for Clinical Trials in Oncology, to investigate frontline therapy for older patients with CLL, with the goal of really trying to determine what is the optimal therapy for this patient group.

Related Videos

Colorectal Cancer

Cathy Eng, MD, and Lars Henrik Jensen, MD, PhD, on Locally Advanced Colon Cancer: Efficacy of Neoadjuvant Chemotherapy and Standard Treatment

Cathy Eng, MD, of Vanderbilt-Ingram Cancer Center, and Lars Henrik Jensen, MD, PhD, of the Danish Colorectal Cancer Center South and the University Hospital of Southern Denmark, discuss phase III results from the Scandinavian NeoCol trial, which showed that neoadjuvant chemotherapy is not superior to standard upfront surgery in terms of disease-free and overall survival in patients with colon cancer, although there are certain circumstances when this approach may have more favorable outcomes (Abstract LBA3503).

Myelodysplastic Syndromes

Amer Methqal Zeidan, MBBS, MHS, on Myelodysplastic Syndromes: New Data From the IMerge Study of Imetelstat

Amer Methqal Zeidan, MBBS, MHS, of Yale University and Yale Cancer Center, discusses phase III findings on the first-in-class telomerase inhibitor imetelstat, which was given to patients with heavily transfusion-dependent non-del(5q) lower-risk myelodysplastic syndromes that are resistant to erythropoiesis-stimulating agents. Imetelstat resulted in a significant and sustained red blood cell (RBC) transfusion independence in 40% of these heavily transfused patients. The response was also durable and accompanied by an impressive median hemoglobin rise of 3.6 g/dL, and seen in patients with and without ring sideroblasts. Importantly, reduced variant allele frequency was observed in the most commonly mutated myeloid genes which correlated with duration of transfusion independence and hemoglobin rise, therefore suggesting a disease-modifying potential of this agent (Abstract 7004).

Bladder Cancer

Arlene O. Siefker-Radtke, MD, on Metastatic Urothelial Carcinoma: New Data on Erdafitinib vs Chemotherapy From the THOR Study

Arlene O. Siefker-Radtke, MD, of The University of Texas MD Anderson Cancer Center, discusses phase III findings showing that for patients with advanced or metastatic urothelial carcinoma and FGFR alteration who already had been treated with a PD-(L)1 inhibitor, erdafitinib significantly improved overall and progression-free survival, as well as overall response rate, compared with investigator’s choice of chemotherapy (LBA4619).


Reid Merryman, MD, on High-Risk Follicular Lymphoma: New Data on Epcoritamab, Rituximab, and Lenalidomide

Reid Merryman, MD, of Dana-Farber Cancer Institute, discusses his findings on the regimen of epcoritamab plus rituximab and lenalidomide for patients with high-risk follicular lymphoma. Regardless of whether their disease progressed within 24 months of first-line chemoimmunotherapy, this regimen showed antitumor activity and a manageable safety profile in patients with relapsed or refractory disease. Epcoritamab, a subcutaneous T-cell–engaging bispecific antibody, may abrogate the negative effects of high-risk features (Abstract 7506).

Prostate Cancer

Alberto Bossi, MD, on Prostate Cancer: PEACE-1 Trial Findings on Radiotherapy Plus Systemic Treatment

Alberto Bossi, MD, of Institut Gustave Roussy, discusses phase III findings showing that combining prostate radiotherapy with systemic treatment did not improve overall survival in men with de novo metastatic castration-sensitive prostate cancer and low metastatic burden. However, best outcomes (radiographic progression–free-survival and overall survival) were observed in men receiving the standard of care plus abiraterone acetate plus prednisone with radiotherapy (Abstract LBA5000).