Expression of immune checkpoint molecules in bone marrow as a predictor of clinical outcome in myelodysplastic syndrome
Nikolai Y. Tcvetkov, Ivan S. Moiseev, Artem A. Gusak, Vadim V. Baykov, Elena V. Morozova, Boris V. Afanasyev
Raisa Gorbacheva Memorial Research Institute of Pediatric Oncology, Hematology and Transplantation, Pavlov First Saint Petersburg State Medical University, St. Petersburg, Russia
Contacts: Dr. Nikolai Y. Tcvetkov
Myelodysplastic syndrome (MDS) is a heterogeneous group of hematological malignancies affecting mostly elderly people over 70 years. Lack of effective treatment modalities in the field promotes the search for new treatment options with several ongoing clinical trials. The checkpoint inhibitors are also an option since they are able to affect the bone marrow niche, which is involved in MDS development, although there is still no consensus on the optimal use of this method in MDS settings and treatment criteria. The aim of our single-center retrospective study was to determine whether different expression of checkpoint molecules in bone marrow biopsies at diagnosis may affect clinical course of MDS patients.
Materials and methods
A consecutive cohort of 55 MDS patients treated in our center in 2003 to 2018 was studied. Among 55 adult MDS patients, 27 belonged to high or very high risk group, as based on IPSS-R score values. Twenty-three patients subsequently underwent allogeneic bone marrow transplantation. The median follow-up period was 900 days. We developed a technique able to detect expression of the following antigens: PD-1, PD-L1, PD-L2, LAG-3, Galectin-9, TIM-3, CD80. The relations between expression level and clinical outcomes were analyzed. Three-year overall and relapse-free survival and time-to-progression were assessed as the main clinical outcomes. Our univariate analysis was aimed to assess the possible role of overall checkpoint expression level and age, IPSS/WPSS/IPSS-R scores, blood and blast counts, transfusion dependency. The SAS 9.4 software was used, p-value of less than 0.05 was considered statistically significant. The study was approved by local Ethics Committee.
Intensive expression of TIM-3 was observed in 100% of cases. Also, in most cases, moderate Gal-9 expression was observed on many cells. Our statistical analysis yielded a significant connection between CD80 expression and three-year time-to-progression. At 3-year follow-up disease progression was seen in 72.9% of patients with CD80 level of more than 1 point and 52.1% of patients with CD80 level of less than 1 point (p=0.04). Similar trend was seen for general checkpoint expression level. At 3-year follow-up, 67.2% of patients with checkpoint expression level of more than 1.5 point showed the disease progression, while in the group with checkpoint expression level of less than 1.5 point, the progression was seen only in 33.3% of cases (p=0.059).
Our preliminary study highlighted a potential role of immune checkpoint molecules in MDS pathogenesis and a need for further studies of different immune checkpoint inhibitors.
This work was supported by Russian Science Foundation, grant № 17-75-20145. Authors confirm the absence of any conflicts of interests.
Myelodysplastic syndrome, checkpoint molecules, expression.