Response to anti-SARS-CoV-2 mRNA vaccines in multiple myeloma and chronic lymphocytic leukemia patients.

Multiple myeloma (MM) and chronic lymphocytic leukemia (CLL) patients have increased morbidity and mortality rates of COVID-19 due to immunosuppression associated with the disease and ongoing therapy. The same immune impairment accompanying CLL and MM also affects suboptimal vaccine response. The study assessed the effectiveness of the humoral and T cell-mediated immunity following mRNA COVID-19 vaccination (using either BNT162b2 or mRNA-1273) in short-term (2-5 weeks after second dose) and long-term follow-up (12 weeks after vaccination). Between March and August 2021, blood samples were obtained from 62 CLL and 60 MM patients from eight different hematology departments in Poland. Total anti-RBD antibodies were detected in 37% MM patients before vaccination, increased to 91% and 94% in short- and long-term follow-up, respectively. In CLL, serological responses were detectable in 21% of patients before vaccination and increased to 45% in the short-term and 71% in long-term observation. We detected a tendency to higher frequencies of specific CD8+ T cells against SARS-CoV-2 after vaccination compared to samples before vaccination in MM patients and no changes in frequencies of specific T cells in CLL patients. Our study provides novel insights into mRNA vaccination efficacy in immunocompromised MM and CLL patients, and our findings highlight that specific CD8+ T cells against SARS-CoV-2 might be induced by vaccination but do not correlate positively with serological responses.

Genetics, Genomics and Emerging Molecular Therapies of Pancreatic Cancer.

The number of cases of pancreatic cancers in 2019 in Poland was 3852 (approx. 2% of all cancers). The course of the disease is very fast, and the average survival time from the diagnosis is 6 months. Only <2% of patients live for 5 years from the diagnosis, 8% live for 2 years, and almost half live for only about 3 months. A family predisposition to pancreatic cancer occurs in about 10% of cases. Several oncogenes in which somatic changes lead to the development of tumours, including genes BRCA1/2 and PALB2, TP53, CDKN2A, SMAD4, MLL3, TGFBR2, ARID1A and SF3B1, are involved in pancreatic cancer. Between 4% and 10% of individuals with pancreatic cancer will have a mutation in one of these genes. Six percent of patients with pancreatic cancer have NTRK pathogenic fusion. The pathogenesis of pancreatic cancer can in many cases be characterised by homologous recombination deficiency (HRD)-cell inability to effectively repair DNA. It is estimated that from 24% to as many as 44% of pancreatic cancers show HRD. The most common cause of HRD are inactivating mutations in the genes regulating this DNA repair system, mainly BRCA1 and BRCA2, but also PALB2, RAD51C and several dozen others.

The cancer-risk variant frequency among Polish population reported by the first national whole-genome sequencing study.

Introduction: Population-based cancer screening has raised many controversies in recent years, not only regarding the costs but also regarding the ethical nature and issues related to variant interpretation. Nowadays, genetic cancer screening standards are different in every country and usually encompass only individuals with a personal or family history of relevant cancer. Methods: Here we performed a broad genetic screening for cancer-related rare germline variants on population data from the Thousand Polish Genomes database based on 1076 Polish unrelated individuals that underwent whole genome sequencing (WGS). Results: We identified 19 551 rare variants in 806 genes related to oncological diseases, among them 89% have been located in non-coding regions. The combined BRCA1/BRCA2 pathogenic/likely pathogenic according to ClinVar allele frequency in the unselected population of 1076 Poles was 0.42%, corresponding to nine carriers. Discussion: Altogether, on the population level, we found especially problematic the assessment of the pathogenicity of variants and the relation of ACMG guidelines to the population frequency. Some of the variants may be overinterpreted as disease-causing due to their rarity or lack of annotation in the databases. On the other hand, some relevant variants may have been overseen given that there is little pooled population whole genome data on oncology. Before population WGS screening will become a standard, further studies are needed to assess the frequency of the variants suspected to be pathogenic on the population level and with reporting of likely benign variants.