Introduction: Programmed death receptor-1 blockade with pembrolizumab is approved by the US Food and Drug Administration to treat patients with metastatic melanoma. Activating T cells to fight cancer may cause immune-mediated adverse events. Pembrolizumab-induced pancytopenia has not been previously reported in the medical literature, to our knowledge.Case Presentation: A 52-year-old Caucasian woman with a diagnosis of metastatic melanoma of the rectum experienced multiple adverse events along her course of therapy with pembrolizumab, ranging from colitis, hepatitis, gastritis, and vitiligo after the fifth cycle of pembrolizumab; to knee synovitis after the 14th cycle; and to severe pancytopenia after the 18th cycle of pembrolizumab. Severe pancytopenia improved after high-dose corticosteroids and a 5-day course of intravenous immunoglobulin therapy.Discussion: In our case, pembrolizumab-induced Grade 4 pancytopenia resolved via a combination of corticosteroids and intravenous immunoglobulins. Pancytopenia reached a nadir in 10 weeks, and it took 16 weeks for meaningful recovery.

187 Background: Older age is a risk feature in melanoma. Elderly are more likely to have immunosenescence, which could help melanoma cells escape immune surveillance. Hence, there is a belief that elderly people cannot mount a potent immune response to checkpoint inhibitors (CPI) to fully eliminate melanoma. The objective of the study was to investigate age-related differences in the time to progression (TTP), overall survival (OS), and immunotherapy related adverse events (irAEs) among patients with metastatic melanoma who received CPI. Methods: We retrospectively identified patients with stage IV melanoma who received at least 1 dose of ipilimumab, pembrolizumab, nivolumab, or combined ipilimumab and nivolumab. Demographics, pathologic, and clinical characteristics were obtained. Immune-related response criteria were utilized to define responses. Results: Sixty patients were included; 29 were less than 65 years old and 31 were 65 years or older. No significant differences, when adjusted for gender, type of melanoma and presence of brain metastasis, in TTP [HR 0.79; 95% CI (0.371.70); p = 0.46] and OS [Hazard ratio (HR) 0.75; 95% CI (0.31-1.82); P = 0.491] was observed between the < 65 and ≥65 year-old groups who received CPI for metastatic melanoma. Overall irAEs in two groups was comparable with 62% in the younger patients and 45% in the older patients (P = 0.19). Thirty responders had a median age of 66.9 (54.3-73.3 years old) and 30 non-responders had a median age of 62.7 (54-69.1 years old). Non-responders, regardless of age, were more likely to have BRAF mutated melanomas (53.3% vs. 27.6%; P = 0.04) and less likely to have irAEs (40% vs. 66.7%; P = 0.04) than responders. Conclusions: No difference in TTP, OS or irAEs was observed between the elderly and the young patients who received CPI for metastatic melanoma. In general, responders had higher irAEs and less BRAF mutated melanomas than non-responders.

Multiple myeloma (MM) patients frequently attain a bone marrow (BM) minimal residual disease (MRD) negativity status in response to treatment. We identified 568 patients who achieved BM MRD negativity following autologous stem cell transplantation (ASCT) and maintenance combination therapy with an immunomodulatory agent and a proteasome inhibitor. BM MRD was evaluated by next generation flow cytometry (sensitivity of 10-5 cells) at 3 to 6 months intervals. With a median follow up of 9.9 years from diagnosis (range, 0.4 - 30.9), 61% of patients maintained MRD negativity, while 39% experienced MRD conversion at a median of 6.3 years (range, 1.4 - 25). The highest risk of MRD conversion occurred within the first 5 years after treatment and was observed more often in patients with abnormal metaphase cytogenetic abnormalities (95%vs. 84%; P = 0.001). MRD conversion was associated with a high risk of relapse and preceded it by a median of 1.0 year (range, 0 - 4.9). However, 27% of MRD conversion positive patients had not yet experienced a clinical relapse with a median follow-up of 9.3 years (range, 2.2 - 21.2). Landmark analyses using time from ASCT revealed patients with MRD conversion during the first 3 years had an inferior overall and progression-free survival compared to patients with sustained MRD negativity. MRD conversion correctly predicted relapse in 70%, demonstrating the utility of serial BM MRD assessment to complement standard laboratory and imaging to make informed salvage therapy decisions.

Introduction Cetuximab, a chimeric monoclonal antibody, is a commonly used anticancer drug that prevents binding of epidermal growth factor to epidermal growth factor receptor. It has been widely used in a variety of cancers since its initial approval by the FDA in 2004. Despite its efficacy, it has met with some genuine concerns especially regarding the anaphylactoid reactions occurring after first infusions. Cetuximab-related first infusion reaction has been found to be much more prevalent in the Southeastern United States with several studies from the southern United States supporting it. The purpose of our study was to determine the rate of first infusion reaction in the state of Arkansas and the factors that could predispose to first infusion reaction. Methods and results We performed a retrospective chart review of consecutive patients who received cetuximab between January 2004 and December 2016 at the University of Arkansas for Medical Sciences. We included a total of 220 patients in our analysis out of which 32 (14.5%) developed cetuximab-related first infusion reaction. There was a statistically significant increased risk in males versus females (18.2% vs. 8.4%, P = 0.045) and trend toward significance for the difference between Caucasians and Blacks (16.5% vs. 7.1%, P = 0.054). Conclusion There is increased incidence of cetuximab-related first infusion reaction in Arkansas which is much higher than the national average but comparable to the incidence in other neighboring states in the Southeastern United States. This increased incidence tends to cluster in Caucasian males. Safer alternatives should be preferred for treatment of cancers particularly in the Southeastern United States whenever possible.

Hemolytic uremic syndrome (HUS) is a type of thrombotic microangiopathy syndrome (TMA) defined as a triad of non-immune microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Shiga toxin (Stx) or diarrhea-associated HUS is one of the major categories of secondary HUS, which is seen predominantly in children and is regarded as a rare entity in the adult population. We present two cases of sporadic Stx or diarrhea-associated HUS in adult females. Our first case is a 74-year-old Caucasian woman who presented to the emergency department with nausea, vomiting, and bloody diarrhea for five days. The patient reported a history of consuming meatloaf from a local store three days prior to the onset of symptoms. On presentation, laboratory workup was consistent with hemolytic anemia, thrombocytopenia, and acute kidney injury. Thrombocytopenic purpura was ruled out with normal ADAMTS13 activity. The patient’s kidney function improved and the platelet count recovered to normal with supportive measures and did not require renal replacement therapy. In the second case, we describe a 79-year-old Caucasian woman with a history of metastatic lung cancer who presented with abdominal pain, nausea, vomiting, and bloody diarrhea. History was positive for consuming meat from a local restaurant a day prior to the onset of symptoms. Initial laboratory work showed severe thrombocytopenia, microangiopathic hemolytic process, and acute kidney injury requiring continuous renal replacement therapy. Due to the unfavorable prognosis of her metastatic lung cancer, the patient and the family members decided to opt for hospice care and she was subsequently transferred to the inpatient hospice. Diarrhea-associated HUS or Stx-HUS is a relatively underreported entity among the adult population. The treatment of typical or Stx-HUS is mainly supportive, but it is critical to rule out other causes of TMAs, especially thrombotic thrombocytopenic purpura (TTP), as it is a medical emergency that requires prompt plasmapheresis.