AUTHOR=Klausen Uffe , Grauslund Jacob Handlos , Jørgensen Nicolai Grønne Dahlager , Ahmad Shamaila Munir , Jonassen Merete , Weis-Banke Stine Emilie , Martinenaite Evelina , Pedersen Lone Bredo , Lisle Thomas Landkildehus , Gang Anne Ortved , Enggaard Lisbeth , Hansen Morten , Holmström Morten Orebo , Met Özcan , Svane Inge Marie , Niemann Carsten Utoft , Pedersen Lars Møller , Andersen Mads Hald 

TITLE=Anti-PD-L1/PD-L2 therapeutic vaccination in untreated chronic lymphocytic leukemia patients with unmutated IgHV

JOURNAL=Frontiers in Oncology

VOLUME=Volume 12 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.1023015

DOI=10.3389/fonc.2022.1023015

ISSN=2234-943X

ABSTRACT=Chronic lymphocytic leukemia (CLL) patients with unmutated immunoglobulin heavy chain (IgHV) are at risk of early disease progression compared to patients with mutated IgHV. As a preventive strategy we treated 19 previously untreated CLL patients with unmutated IgHV in a phase 1/2 trial (clinicaltrials.gov, NCT03939234) exploring the efficacy and toxicity of a therapeutic cancer vaccine containing peptides derived from programmed death ligand 1(PD-L1) and ligand 2 (PD-L2) hoping to restore immunological control of the disease. According to the iwCLL no patients obtained a response, however during follow-up one patient had complete normalization of the peripheral lymphocyte count and remained in hematological remission during a follow up time of currently 15 months. At end of treatment one patient had progressed, and seventeen patients had stable disease. During follow up with a median time of 23,5 months since inclusion seven patients had progressed and eight patients had stable disease. Notably, the median time to first treatment (TTFT) from diagnosis was 90,3 months with since diagnosis with a median follow up time of 50,1 months. More than 80 % of patients obtained vaccine specific immune responses confirming the immunogenicity of the vaccine. The vaccine was generally well tolerated with only grade I-II adverse events. Although there were some signs of clinical effects the favorable outcome in TTFT needs to be investigated in a randomized setting. The efficacy of the vaccine should preferably be tested in combination with novel targeted therapies or as a consolidating treatment.