Poster Presentation MIN Spring Retreat 2023

Immunological Changes in Marginal Zone Lymphoma Patients Undergoing Combination Therapy with Venetoclax and Ibrutinib: Insights from a Longitudinal Study (#106)

Hong Han (Lina) Le 1 2 , Joanne E Davis 1 2 , Mandy Ludford-Menting 1 2 , Sasanka M Handunnetti 2 3 , Constantine S Tam 2 3 , Rachel M Koldej 1 2 , David S Ritchie 1 2 3
  1. ACRF Translational Research Laboratory, Royal Melbourne Hospital, Melbourne, VIC, Australia
  2. Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, VIC , Australia
  3. Department of Clinical Haematology, Peter MacCallum Cancer Centre–Royal Melbourne Hospital, Melbourne, VIC, Australia

1. Background

Marginal Zone Lymphoma (MZL) is a prevalent slow-growing Non-Hodgkin Lymphoma, accounting for 7% of total cases annually. There is still no curative approach for MZL, and patients often require recurring therapies. Molecular targeted therapy using a combination of Venetoclax and Ibrutinib has shown success in relapsed/refractory settings; however, the long-term impact on patient immunology remains unknown.

This research examines the immunological changes in MZL patients participating in the AIM study conducted at the Peter MacCallum Cancer Centre and Royal Melbourne Hospital, who received a combination of Ibrutinib and Venetoclax treatment over four years. The findings of this study contribute to the knowledge of MZL pathogenesis, leading to improved patient outcomes, and advancing lymphoma research. The AIM trial was registered at www.clinicaltrials.gov as #NCT02471391.

 

2. Methodologies

Human peripheral blood mononuclear cells from 10 aged-matched healthy donors (average age 62.6 years old) were provided by The Australian Red Cross Blood Service, which served as the reference for the baseline expression of various immune cell types. 15 MZL patients (average age 66.7 years old) were collected at several time points over four years. Spectral cytometry was used to evaluate immune subsets.

 

3. Results

Longitudinal analysis of MZL patients demonstrated dysregulated immune cell subsets and checkpoint marker expression before commencing the AIM trial. Treatment with Venetoclax and Ibrutinib induced a statistically significant decrease in B cells and an increase in myeloid cell compartments, the associated checkpoint markers, particularly pDC and monocytes. Interestingly, unlike Mantle Cell Lymphoma (MCL)1, longitudinal MZL samples did not show a significant change in the lymphoid immune cell subsets during Venetoclax and Ibrutinib treatment, suggesting distinct immune dysfunction between MCL and MZL.

 

4. Summary

This longitudinal study provides valuable insights into the immunological changes associated with Venetoclax and Ibrutinib treatment in MZL patients, advancing the understanding of MZL pathogenesis.

  1. Davis J, Handunnetti S, Ludford-Menting M, Sharpe C, Blombery P, Anderson M et al. Immune recovery in patients with mantle cell lymphoma receiving long-term ibrutinib and venetoclax combination therapy. Blood Advances. 2020;4(19):4849-4859.