TY - JOUR
T1 - Anti-PD-L1/PD-L2 therapeutic vaccination in untreated chronic lymphocytic leukemia patients with unmutated IgHV
AU - Klausen, Uffe
AU - Grauslund, Jacob Handlos
AU - Jørgensen, Nicolai Grønne Dahlager
AU - Ahmad, Shamaila Munir
AU - Jonassen, Merete
AU - Weis-Banke, Stine Emilie
AU - Martinenaite, Evelina
AU - Pedersen, Lone Bredo
AU - Lisle, Thomas Landkildehus
AU - Gang, Anne Ortved
AU - Enggaard, Lisbeth
AU - Hansen, Morten
AU - Holmström, Morten Orebo
AU - Met, Özcan
AU - Svane, Inge Marie
AU - Niemann, Carsten Utoft
AU - Pedersen, Lars Møller
AU - Andersen, Mads Hald
N1 - Copyright © 2022 Klausen, Grauslund, Jørgensen, Ahmad, Jonassen, Weis-Banke, Martinenaite, Pedersen, Lisle, Gang, Enggaard, Hansen, Holmström, Met, Svane, Niemann, Pedersen and Andersen.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85143346823&partnerID=8YFLogxK
U2 - 10.3389/fonc.2022.1023015
DO - 10.3389/fonc.2022.1023015
M3 - Journal article
C2 - 36483037
SN - 2234-943X
VL - 12
SP - 1
EP - 13
JO - Frontiers in Oncology
JF - Frontiers in Oncology
M1 - 1023015
ER -