Advertisement


Yucai Wang, MD, PhD, on Richter Transformation of CLL: Findings on Combination Therapy With an Immune Checkpoint Inhibitor

2024 ASCO Annual Meeting

Advertisement

Yucai Wang, MD, PhD, of the Mayo Clinic, discusses the increased efficacy of combination therapy with pembrolizumab plus a BCR kinase inhibitor compared with pembrolizumab alone in patients with Richter transformation of chronic lymphocytic leukemia (CLL; Abstract 7050).



Transcript

Disclaimer: This video transcript has not been proofread or edited and may contain errors.
So, Richter's transformation is a rare but devastating complication of chronic lymphocytic leukemia or small lymphocytic lymphoma. The prognosis of this disease is poor without established standard of care treatments. Our institution did a phase two clinical trial investigating the efficacy of pembrolizumab in this disease. Previously, we have reported preliminary efficacy results of this trial. So in the first nine patients with Richter's transformation, we observed a response rate of 44%. In this updated analysis, we report updated efficacy data of single-agent pembrolizumab and the combination therapy with pembrolizumab and a BCR inhibitor. So in this trial, patients were first treated with single-agent pembrolizumab every three weeks for up to 12 months. Patients who only have stable disease after three cycles of treatment or those who progress at any time during this single-agent treatment phase can add a inhibitor of the B-cell receptor, either with a BTK inhibitor or a PI3K inhibitor. So in this updated analysis, we enrolled a total of 26 patients, nine in the initial cohort, as reported a number of years earlier, and 17 in an expansion cohort. Looking at the patient and the disease baseline characteristics, this is consistent with what you would observe in this patient population. To highlight, most of the patients had unmutated IgHV and about 40% of the patients had TP53 alterations. This is a heavily pretreated population with a median of three lines of prior therapy, with up to 11 lines of therapy for CIL and five lines of therapy for Richter's transformation. Over half of the patients were previously exposed to BTK inhibitor ibrutinib already, and the massive majority of those patients actually had disease progression on this agent. So again, a high-risk patient population, difficult to treat. So in this trial, we observed that with single-agent pembrolizumab treatment, the objective response rate was 23%, or six out of 26 responses. It was two CR and 4 PRs. What's interesting is that for the 16 patients who went on to receive a doublet therapy with pembrolizumab either in combination with ibrutinib or idelalisib, we saw a high response rate of over 60%. So again, these are patients who progressed through pembrolizumab, and most of the patients have been previously exposed to ibrutinib, so this 60% response rate is very encouraging. In terms of survival outcomes, in a single-agent phase they observed the median progression-free survival was three months, and the median progression-free survival in the doublet therapy phase was about eight months. In total, the median overall survival is about one year, and the overall survival rate at two years is 27%. So again, in this heavily pretreated population with high-risk disease features, this doublet therapy certainly looks very encouraging in inducing a response and to maintain that. So these data do suggest that a PD-L1 blockade in combination with a BCR inhibitor is efficacious in treating Richter's transformation and it warrants further exploration. We do have another ongoing trial examining the combination of PD-L1 blockade in combination with a BTK inhibitor and the venetoclax in this patient population, and we look forward to sharing those results in the future.

Related Videos

Prostate Cancer
Genomics/Genetics

Alicia Morgans, MD, MPH, and Susan Halabi, PhD, on Prostate Cancer: New Findings on Classifying Patients Into Risk Groups

Alicia Morgans, MD, MPH, of Dana-Farber Cancer Institute, and Susan Halabi, PhD, of the Duke Cancer Institute and Duke University School of Medicine, discuss a clinical-genetic model that identified novel circulating tumor DNA alterations that are prognostic of overall survival and may help to classify patients with metastatic castration-resistant prostate cancer into risk groups useful for selecting trial participants (Abstract 5007).

Palliative Care

Joseph A. Greer, PhD, on Lung Cancer: Telehealth vs In-Person Palliative Care

Joseph A. Greer, PhD, of Massachusetts General Hospital and Harvard Medical School, discusses study findings showing the merits of delivering early palliative care via telehealth vs in person to patients with advanced lung cancer. Using telemedicine in this way may potentially improve access to and more broadly disseminate this evidence-based care model (LBA3).

Breast Cancer

Sherene Loi, MD, PhD, on Early-Stage Breast Cancer: Weighing the Prognostic Value of ctDNA Detection

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).

Clifford A. Hudis, MD, and Karen E. Knudsen, MBA: An ASCO–American Cancer Society Partnership to Benefit Patients

Clifford A. Hudis, MD, CEO of the American Society of Clinical Oncology (ASCO), and Karen E. Knudsen, MBA, CEO of the American Cancer Society, discuss a newly launched collaboration between the organizations to make it simpler for patients to find authoritative cancer information online. The effort creates one of the largest and most comprehensive online resources for credible cancer information, available for free to the public on cancer.org.

 

Multiple Myeloma

Paula Rodríguez-Otero, MD, PhD, and Amrita Y. Krishnan, MD, on Multiple Myeloma: Moving BCMA-Directed Therapies to Earlier Use

Paula Rodríguez-Otero, MD, PhD, of Spain’s Cancer Center Clínica Universidad de Navarra, and Amrita Y. Krishnan, MD, of the City of Hope Cancer Center, discuss two key studies on B-cell maturation antigen (BCMA)-directed therapies: CARTITUDE-4 on ciltacabtagene autoleucel in patients with functional high-risk multiple myeloma; and DREAMM-7 on belantamab mafodotin-blmf plus bortezomib and dexamethasone vs daratumumab, bortezomib, and dexamethasone in patients with relapsed or refractory disease.

Advertisement

Advertisement




Advertisement