Jia Ruan, MD, PhD, on Mantle Cell Lymphoma: Phase II Findings on Acalabrutinib/Lenalidomide/Rituximab
2022 ASH Annual Meeting and Exposition
Jia Ruan, MD, PhD, of Meyer Cancer Center, Weill Cornell Medicine, and NewYork-Presbyterian Hospital, discusses trial results demonstrating that the triple chemotherapy-free combination of acalabrutinib, lenalidomide, and rituximab is well tolerated, highly effective, and produces high rates of minimal residual disease (MRD)-negative complete response as an initial treatment for patients with mantle cell lymphoma, including those with TP53 mutations. Real-time MRD analysis may enable treatment de-escalation during maintenance to minimize toxicity, which warrants further evaluation. An expansion cohort of acalabrutinib/lenalidomide/obinutuzumab is being launched (Abstract 73).
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
The purpose of the study is to evaluate the safety and efficacy of this triplet combination. This triplet combination is built upon our previous report of doublet, which is lenalidomide plus rituximab. It has shown very high response rate and durability of the response, so we would like to see if the addition of a next-generation BTK inhibitor would continue to improve efficacy meanwhile, also maintain or improve safety profile. The other purpose of the study is to evaluate the minimal residual disease status, which is a molecular response with the next-generation sequencing-based assay platform clonoSEQ to evaluate the quality of the response in a real-time base because there's a previous study that suggests the quality of the response measured by minimal residual disease correlate with progression-free survival. So, therefore, we want to see how our triplet combination would improve the response quality measured by minimal residual disease.
And the last purpose of the study is to see, based on the MRD result, can we adjust our treatment strategy, particularly in terms of its intensity and duration, especially, in those patient who can achieve MRD-negative complete remission. The finding of our study has shown that this triplet combination is well tolerated with the expected side effects profile. In addition, it also seems to be highly effective measured by both the response rate using Lugano criteria, as well as minimal residual disease measured by clonoSEQ technology. So a hundred percent of our patients achieved response on study, and the Lugano complete remission rate was 83% measured by the clonoSEQ minimal residual disease, which we defined the threshold of less than one in a million.
About 50% of our patient achieve MRD-negative remission after 12 cycles of treatment, and 67% achieved molecular remission in peripheral blood after 12 cycles of treatment, and 83% after 24 cycles of treatment on the triplet. In addition, we have also evaluated the possibility and the feasibility of de-escalation of our treatment after 24 cycles of triplet therapy by discontinuing acalabrutinib and lenalidomide for those patients in molecular remission. We're very pleased with our preliminary findings and we hope that the results of the study could further contribute to providing options for a patient who's seeking chemotherapy, free combinations with highly effective biological combinations. Furthermore, we're hoping to explore the feasibility of limiting the chronic use of biological agents, but use MRD as a evaluation point to guide our treatment strategy.
Stephen M. Ansell, MD, PhD, and Patrizia Mondello, MD, PhD, both of the Mayo Clinic, discuss the 20% of patients with follicular lymphoma (FL) who relapse early and experience a poor prognosis. The researchers found that FLs with high levels of IRF4 expression are associated with a suppressive tumor microenvironment, and selective IRF4 silencing restores antilymphoma T-cell immunity. Further investigation is warranted to identify the mechanisms by which IRF4 controls tumor immunity to develop precision therapies for this population (Abstract 70).
Tomohiro Aoki, MD, PhD, of the University of British Columbia and the Centre for Lymphoid Cancer at BC Cancer, discusses a novel prognostic model applicable to patients with relapsed or refractory classical Hodgkin lymphoma who were treated with autologous stem cell transplantation. The model has shown the interaction between the biomarker CXCR5 on HRS cells (Hodgkin and Reed/Sternberg cells, hallmarks of Hodgkin lymphoma) with specific follicular T helper cells and macrophages, a prominent crosstalk axis in relapsed disease. This insight opens new avenues to developing predictive biomarkers (Abstract 71).
Eileen M. Boyle, MD, PhD, of the Perlmutter Cancer Center, NYU Langone Health, discusses Fc-mediated antibody effector function, inflammation resolution, and oligoclonality and their role in predicting sustained measurable residual disease negativity in patients with newly diagnosed multiple myeloma who were treated with immunotherapy regimens. For the first time, an analysis of T-cell receptors shows that oligoclonal profiles seen on treatment may influence the fitness of the immune response (Abstract 100).
Eunice S. Wang, MD, of Roswell Park Comprehensive Cancer Center, discusses the outcomes of patients newly diagnosed with acute myeloid leukemia (AML) who were treated with cytarabine plus daunorubicin plus gemtuzumab ozogamicin (GO). These patients experienced higher rates of measurable residual disease–negative complete remission and complete remission with incomplete count recovery, compared to those treated with cytarabine plus idarubicin daunorubicin alone. Although adding GO was not associated with improved overall survival, longer follow-up is warranted to determine an absolute survival advantage of this regimen (Abstract 58).
Anand P. Jillella, MD, of Georgia Cancer Center at Augusta University, discusses results from the ECOG-ACRIN EA9131 Trial, which showed that using a simplified treatment algorithm and management recommendations made by a group of specialists, resulted in a dramatic improvement in 1-year survival of patients with acute promyelocytic leukemia (Abstract 421).