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

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 International Workshop on Chronic lymphocytic Leukemia (iwCLL) response criteria, no patients obtained a response; however, during follow-up, one patient had complete normalization of the peripheral lymphocyte count and remained in biochemical remission after a follow-up time of 15 months. At the end of treatment, one patient had progressed, and 17 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. The median time to first treatment (TTFT) from diagnosis was 90.3 months with a median follow-up time of 50.1 months. This apparent favorable outcome in TTFT needs to be investigated in a randomized setting, as our population may have been biased. 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 vaccine seems to be insufficient as monotherapy in CLL, possibly due to a high tumor burden. The efficacy of the vaccine should preferably be tested in combination with novel targeted therapies or as a consolidating treatment.

Informations de copyright

Copyright © 2022 Klausen, Grauslund, Jørgensen, Ahmad, Jonassen, Weis-Banke, Martinenaite, Pedersen, Lisle, Gang, Enggaard, Hansen, Holmström, Met, Svane, Niemann, Pedersen and Andersen.

Déclaration de conflit d'intérêts

The first author UK was employed at National Center for Cancer Immune Therapy CCIT-DK, supported by a research agreement with IO biotech APS during the trial. Further, the study is part of a PhD thesis by UK, who answers to MA, his primary supervisor and employer. MA is named as an inventor on various patent applications relating to therapeutic uses of PD-L1 and PD-L2 peptides. These patent applications are assigned to the company IO Biotech, which is developing immune-modulating cancer treatments. MA and IS have cofounded IO Biotech and are shareholders and active advisors in the company. CN received research funding and/or consultancy fees outside this study from AbbVie, AstraZeneca, Janssen, CSL Behring, BeiGene, Genmab, Takeda, and Octapharma. Large parts of the study have taken place at CCIT-DK, which is an organization that has an economical interest in the tested vaccines according to the patent laws in Denmark. JG, SW-B, SA, MH, MOH, and ÖM were employed at CCIT-DK during the trial, answering to either IMS or MHA. EM is an employee at IO Biotech. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.