Nivolumab-induced immune-related neutropenia in a renal cell carcinoma patient.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) have considerably improved the prognosis of solid tumors. However, this class of medications can cause immune-related adverse events, which represent a distinct spectrum of adverse events in cancer treatment. CASE REPORT: Here we present a case of immune-related neutropenia (irN) that occurred in a 47-year-old man with metastatic clear cell renal cell carcinoma (ccRCC). During the 18 months of nivolumab monotherapy, severe neutropenia occurred. Buccal mucosal aphthous ulcers and antineutrophil cytoplasmic antibody positivity concurrently emerged with neutropenia. The patient was diagnosed with irN after a comprehensive evaluation ruled out all other likely causes. MANAGEMENT AND OUTCOME: Neutropenia improved with corticosteroids, but reoccurred with the introduction of nivolumab. During the approximately nine-month follow-up period after nivolumab treatment was permanently discontinued due to neutropenia, there was no disease progression. DISCUSSION: IrN associated with nivolumab treatment for metastatic ccRCC is uncommon. The pathophysiology of irN is not entirely understood. Corticosteroids are one of the most commonly used drugs for the treatment of irN. As ICIs become more widely used, medical oncologists will encounter this side effect more frequently.

The relationship between clinicopathological parameters and PD-L1 expression level in advanced stage non-small cell lung cancer.

Introduction: Clinicopathological parameters related to programmed death ligand 1 (PD-L1) expression levels have been investigated in several studies. However, the results of these studies are conflicting and vary in different populations. This study aimed to investigate the relation of clinicopathological parameters with PD-L1 expression level in advanced stage non-small cell lung cancer patients. Materials and Methods: The patients diagnosed with non-small cell lung cancer were enrolled, retrospectively. The data of clinicopathological parameters was collected. Clinicopathological parameters in relation to PD-L1 expression levels (0%, 1-50%, and >50%) were analyzed as univariable and multivariable. Result: In total, 384 patients were enrolled. PD-L1 expression in tumor cells was between 1-50%, and >50% in 41.4%, and 23.4% of patients, respectively. There was no PD-L1 expression in 35.2% of the patients. In univariable analysis, we found that the parameters associated with PD-L1 expression levels revealed that metastatic site number, the subtype of cancer, diagnostic material type, platelet number, and LDH level were statistically significant. Adenocarcinoma frequency was higher in tumors that had PD-L1 expression >50% than in tumors that did not express PD-L1 and the difference was statistically significant (p= 0.04, coefficient= 0.3, 95% CI 0.09-0.94). Cytology as diagnostic material was significant in PD-L1 level 1-50% comparing to >50% (p= 0.02, coefficient= 2.2, 95% CI= 1.08-4.46). Conclusions: According to the results of our study, many of the clinicopathological parameters are not related to the PD-L1 level. The histological subtype and diagnostic material may affect the level of PD-L1 expression.

Characteristic features and prognostic factors in gastric cancer patients with bone metastases: multicenter experience.

We evaluated the incidence, clinicopathological features, prognostic factors, progression-free survival (PFS) and overall survival (OS) of patients with gastric cancer and bone metastases. The medical records of 110 patients with bone metastases were retrospectively analyzed. In our study, the incidence of bone metastases was 3.2%. The median patient age was 60 years. A total of 68 (61.8%) patients exhibited synchronous metastases, and 42 (38.2%) patients developed metachronous metastases. Alkaline phosphatase (ALP) levels were high in 54 (49%) patients. At the median follow-up time of 9.8 months, median PFS and OS times were 4.7 and 6.3 months, respectively. The median interval from the diagnosis to bone metastases was 9.3 months. Univariate analysis showed that Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥2, stage at diagnosis, time of metastases, number of metastases, presence of extraskeletal metastases, use of zoledronic acid treatment, palliative chemotherapy post-bone metastases and radiotherapy to bone metastases were significant prognostic indicators for PFS. Additionally, ECOG PS ≥2, stage at diagnosis, time of metastases, number of metastases, presence of extraskeletal metastases, zoledronic acid treatment, palliative chemotherapy post-bone metastases, and radiotherapy to bone metastases significantly influenced OS. Moreover, in multivariate analysis, ECOG PS, time of metastases, presence of extra-bone metastases, and the use of palliative chemotherapy after bone metastases were found to be independent prognostic factors for PFS. Moreover, ECOG PS, time of metastases, and use of palliative chemotherapy after bone metastases were significantly independent prognostic indicators for OS. Our findings show that the presence of synchronous metastases, use of palliative chemotherapy, use of zoledronic acid after bone metastases, and ALP level within the normal range were significantly associated with prolonged OS in gastric cancer patients with bone metastases.

Prospective Follow-up of Panel Reactive Antibodies From Diagnosis Until Completion of Therapy Including Allogeneic Stem Cell Transplantation Among Patients With Acute Leukemia.

OBJECTIVES: Existence of panel reactive antibodies is the limiting step in both solid-organ and hematopoietic stem cell transplantation. There are hypotheses related to panel reactive antibody formation, but there is no knowledge about its formation in acute leukemia at diagnosis and during the chemotherapy period, in which there is a strong myelosuppression and immunosuppression. We aimed to determine the panel reactive antibodies positivity in acute leukemia patients at diagnosis and during the entire therapy period, including stem cell transplantation. MATERIALS AND METHODS: In this single-center prospective study, we enrolled 35 patients with acute leukemia (8 with acute lymphoblastic leukemia, 27 with acute myeloid leukemia). Serum samples were obtained before induction therapy and every 3 months thereafter until the last follow-up or death, for a median of 369 days (minimum-maximum, 9-725 days). Panel reactive antibodies were defined with single-antigen bead assays on a Luminex platform. RESULTS: A total of 10 patients (29%) were found to have panel reactive antibodies at any time point. At diagnosis, 5 patients (14.3%) had antibodies of either class I (n = 2) or II (n = 1) or both (n = 2), and in 4 patients these persisted during median follow-up of 168 days (minimum-maximum, 9-322 days). Among the remaining 30 patients, an additional 5 (17%) developed de novo antibodies. Incidence rate of development of de novo antibodies was 5.5 per 10 000 person-days. There was no effect of transfusion load on the development of panel reactive antibodies. Differences in percentages in males versus females, blood type mismatch, and graftversus-host disease were higher in patients who had de novo antibodies after transplantation. Positivity at any time had no statistically significant effect on overall survival (P = .71). CONCLUSIONS: Panel reactive antibodies do not occur frequently in the acute leukemia setting despite intensive transfusions.