Chronic lymphocytic leukemia (CLL) is the most commonly diagnosed adult leukemia in the USA and Western Europe. Kidney disease can present in patients with CLL as a manifestation of the disease process such as acute kidney injury with infiltration or with a paraneoplastic glomerular disease or as a manifestation of extra renal obstruction and tumor lysis syndrome. In the current era of novel targeted therapies, kidney disease can also present as a complication of treatment. Tumor lysis syndrome associated with novel agents such as the B-cell lymphoma 2 inhibitor venetoclax and the monoclonal antibody obinutuzumab are important nephrotoxicities associated with these agents. Here we review the various forms of kidney diseases associated with CLL and its therapies.

Survival rates for pancreatic cancer remain dismal. Current standard of care treatment regimens provide transient clinical benefit but eventually chemoresistance develops. Tumors deficient in deoxyribonucleic acid (DNA) damage repair mechanisms such as BRCA mutants show better responses to platinum based agents, however, such tumors can utilize the poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) pathway as a salvage mechanism. Therefore, inhibition of PARP pathway could lead to tumor destruction and synthetic lethality in presence of BRCA mutation. Various PARP inhibitors have been approved for treatment of patients with germline or somatic BRCA mutant breast and ovarian cancer. This provides basis of using PARP inhibitors in patients with pancreatic cancer that harbor BRCA mutation. A recent phase III Pancreas Cancer Olaparib Ongoing (POLO) study showed impressive results with near doubling of progression free survival compared to placebo (7.4 vs 3.8 months). These results highlight the importance of germline testing for all patients with pancreatic cancer and inclusion of additional deficiencies in homologous recombination repair (ATM and PALB2) including BRCA variants of uncertain significance should be further explored.

Myelodysplastic syndromes (MDS) include a heterogeneous group of acquired hematopoietic malignancies characterized by ineffective hematopoiesis, peripheral cytopenias, and a varying propensity for progression to acute myeloid leukemia. The clinical heterogeneity in MDS is a reflection of its molecular heterogeneity. Better understanding of aberrant epigenetics, dysregulation of immune responses, and del(5q) MDS has provided the rationale for well-established treatments in MDS. Further understanding of abnormal signal transduction and aberrant apoptosis pathways has led to development of new rational therapies that are in advanced phases of clinical translation. This review seeks to describe recent developments in our understanding of the pathogenesis of MDS and the potential therapeutic implications of these observations.

Background: New NCCN guidelines recommend germline testing for all patients with confirmed pancreatic cancer (PC) regardless of stage, family history, or ethnicity. PC is linked to inherited cancer susceptibility syndromes, with approximately 10% of cases occurring in the presence of family history. Per SEER statistics, African-Americans (AA) have the highest incidence rate (67% higher) of PC of all ethnic groups and the worse prognosis. Current data links this risk to social and access issues rather than biology. We aim to determine whether the prevalence of germline mutations associated with increased PC susceptibility varies by ethnicity. Methods: We retrospectively examined publicly-available, de-identified, germline and clinical data of patients with a diagnosis of pancreatic cancer (PC) referred to Color Genomics by a healthcare provider for testing of 30 genes associated with hereditary cancer risk. Clinical data included age at diagnosis, sex, self-reported ethnicity, family history of cancer, and personal history of cancer. Ashkenazi Jewish (AJ) ancestry was classified as an ethnic group. Germline genetic variants were classified as pathogenic (P), likely pathogenic (LP), variant of uncertain significance (VUS), likely benign, or benign. Prevalence of P/LP and VUS variants was compared among subgroups classified by age at diagnosis (£ 65 or > 65 years-old), sex, self-reported ethnicity, family history of PC, and personal history of other cancer using chi-square tests. Results: We identified 167 patients with PC of any stage who underwent germline testing. Among these, 47.9% were female and 52.1% male. Ethnic composition was 73.1% Caucasian, 8.4% AJ, 3.6% Hispanic, 3.6% AA, 4.2% Asian, and 7.2% of other or unknown ethnicity. Twenty-four (14.4%) patients carried a P/LP variant, and 45 (26.9%) patients carried a VUS. The most prevalent P/LP variants were BRCA2 (29.6%), ATM (22.2%), and MUTYH (14.8%). APC (18.4%), BRCA2 (14.3%), and ATM (12.2%) were the most prevalent VUS variants. AJ patients had an increased prevalence of P/LP BRCA2 variants (83%, n=5). Ethnicity was significantly associated with risk of carrying any P/LP variant (p = 0.049) but not with a VUS; this association was lost when excluding those of AJ ancestry. Age, sex, family history of PC, and personal history of a second cancer were not associated with risk of carrying any P/LP or VUS variants. Conclusions: Germline mutations are prevalent among PC patients and highest among those of AJ ancestry. Although the prevalence of germline variants is not associated with other ethnic groups, our study highlights the underrepresentation of minorities in germline testing databases, particularly AA. The prevalence of germline variants in minority ethnic groups with PC remains an understudied area and is an example of how barriers to access can limit our understanding of diseases. Further studies are needed to address this critical unmet need. Citation Format: Ana I Velazquez, Carolina Bernabe Ramirez, Daniel H Kwon, Ryan Leibrandt, Narjust Duma. Ethnic disparities among pancreatic cancer patients undergoing germline testing [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr C043.

e23574 Background: FDCS and HS are rare tumors arising from sustentacular cells of the lymph node, rather than lymphocytes. Surgical resection is often employed in case of localized disease, but for unresectable disease, anthracycline-based therapy is commonly used. PD-L1 staining is reportedly positive in 50-80% of FDCS. As a result, we treated 3 patients (pts) with ICI ipilimumab and nivolumab (Ipi/Nivo), and demonstrated the activity of these agents in these rare cancers. Methods: Two FDCS pts and one HS pt, all with B symptoms at the start of treatment, received Ipi/Nivo in the approved dose/schedule (Table). The HS patient was HIV(+) with undetectable viral load on treatment. One FDCS patient received radiation therapy to an active site of disease during immunotherapy. We reimaged patients every 2 months for the first 6 months, then less frequently. PDL-1 IHC and mutation data were available in all cases. Results: Mutation burden varied from low to intermediate; mutations in kinase genes were also observed. Case 1 (FDCS) demonstrated RECIST 1.1 complete response, but also received radiation, and Case 2 (FDCS) had RECIST partial response. Both continue on treatment 9 months after initiation. Case 3 (HS) demonstrated a minor response to treatment, then disease worsened after 4 months, and he subsequently received radiation to the residual site of disease. All patients showed resolution of B symptoms on ICI. Conclusions: We treated these pts with ICI based on their role as antigen presenting cells, as well as their high PD-L1 expression. We speculate that FDCS and related tumors such as HS represent extreme examples of cancers that have evidence of tertiary lymphoid structures, increasingly recognized as important in ICI responsiveness. Prospective clinical trials of ICI in these diagnoses will help us understand the basis of immune responses to ICI in other cancers. [Table: see text]