Background: Immune-related adverse events (irAEs) are secondary reactions related to treatment with immune checkpoint inhibitors (ICIs). There have been six cases published reporting on an association between patients undergoing treatment with ICIs and the occurrence of acquired thrombotic thrombocytopenic purpura (TTP).Case report: We report a 61-year-old male receiving treatment with chemoimmunotherapy followed by pembrolizumab maintenance therapy for advanced non-small-cell lung cancer, presenting with bleeding symptoms, anemia, and thrombocytopenia. The patient received pembrolizumab seven times in total, in three-week cycles. Laboratory testing demonstrated hemolytic anemia, which, in combination with other findings, suggested thrombotic microangiopathy (TMA). PLASMIC scoring and specialized testing with ADAMTS13 activity and inhibitor confirmed a diagnosis of TTP. The patient was started on therapy with plasmapheresis and glucocorticoids, resulting in clinical improvement. The patient chose to leave the hospital under the care of home hospice and died approximately one month after being discharged.Conclusions: Of the six cases of ICI-induced TTP, only one other was treated with pembrolizumab to our knowledge to date. Our patient experienced an adverse reaction marked by thrombocytopenia and hematuria after drug exposure. With symptom improvement after ICI discontinuation and recurrence on readministration, a presumptive diagnosis of ICI-associated TTP was made. This case report and literature review emphasize the need for close observation of patients undergoing ICI therapy for potential rare irAEs. The further investigation aimed at the study of risk factors, disease severity, and treatment response to this form of secondary TTP is needed to guide treatment decisions.
18044 Background: Vorinostat is a small molecule inhibitor of histone deacetylase (HDAC). HDAC inhibitors have shown preclinical activity in lung cancer and are postulated to have an antitumor effect by alteration in acetylation status of histone and non-histone proteins. Methods: Pts with relapsed NSCLC who failed no more than 1 prior cytotoxic therapy were eligible. Treatment: vorinostat, 400 mg po daily in a 21 day cycle. Primary objective: response rate (RR), with goal of at least one responder in first 14 evaluable pts. Secondary objectives: time to progression (TTP), overall survival (OS), safety, and correlative assays. Results: 14 pts enrolled from 12/05- 12/06. Median age 59.5 yrs (range 47–79). 11 females. PS 0:1, 10 pts:4 pts. Thirteen of 14 pts had only 1 prior cytotoxic regimen; 1 pt had only prior erlotinib. Best response to prior treatment: stable disease (SD; 11 pts), progressive disease (PD; 3 pts). Median time since last prior therapy: 2.1 mo (range 0.2–78.5). Vorinostat treatment compliance: 95.8 %. Two pts were not evaluable for response due to not completing Cycle 1 of treatment due to PD. No objective antitumor responses have been seen in the first 12 evaluable pts. Seven pts experienced SD (median 4.2 mo, range 2–10.7). Median TTP: 2.8 mo (range 1–10.7+); median OS 6.5 mo (range 1.4–10.7+); estimated 6 mo OS rate 50% (SE 16%). Grade (Gr) 5 toxicity: CVA (1 pt). Gr 3/4 toxicities: neutropenia (Gr 4–1 pt), lymphopenia (Gr 3–2 pts), fatigue (Gr 3–1 pt), elevated alk phos (Gr 3–1 pt), memory impairment (Gr 3–1 pt), PE/DVT (Gr 3–1 pt; Gr 4–2 pts), dehydration (Gr 3–1 pt). Data from the following correlative studies will be updated: p53 status, gene expression, H3 acetylation, transcription of p21, Nur77, Hsp70, erbB1 and 2, and Akt, cell cycle arrest, and assay of isoprostanes generated by treatment with vorinostat. Conclusions: Vorinostat 400 mg daily is tolerable with more than 80% of patients completing Cycle 1. Vorinostat yields TTP in relapsed NSCLC similar to that of other targeted agents. Although 4 of 14 pts experienced vascular events on treatment, these occurrences are common in this disease setting. At least two additional pts are still to be accrued. Further studies in NSCLC should focus on combining vorinostat with other antitumor agents. No significant financial relationships to disclose.
Patient: Male, 40-year-old Final Diagnosis: Anemia • infectious proctitis • monkeypox Symptoms: Anal pain • rectal bleeding • skin lesion Clinical Procedure: — Specialty: Infectious Diseases Objective: Rare disease Background: A recently described zoonotic viral infection, mpox (monkeypox), is an Orthopoxvirus transmitted by close contact, which causes symptoms similar to smallpox, although less severe. This report presents the case of a 40-year-old man with anemia, proctitis, rectal bleeding, and a perianal rash due to mpox infection. Case Report: A 40-year-old man with a medical history of human immunodeficiency virus (HIV) and syphilis presented multiple times with progressive and painful perianal lesions. On initial presentation, swabbing of the lesions and polymerase chain reaction (PCR) testing confirmed a diagnosis of mpox infection, and treatment with a 14-day course of Tecovirimat was started. Nine days after initiating Tecovirimat, the patient presented again with worsening perianal pain and associated hematochezia resulting in acute symptomatic anemia. Despite a blood transfusion to treat his anemia, the patient’s status declined as his viral symptoms progressed. Computed tomography (CT) investigation demonstrated significant proctitis with interval development of small perianal abscesses. A multidisciplinary approach for medical management and treatment was instituted. The resolution of the patient’s anemia and mpox proctitis was confirmed on follow-up. Conclusions: Despite treatment with antiviral agents, mpox infection can progress quickly; thus, swift management with a multidisciplinary approach and close follow-up is needed to treat and prevent secondary complications such as anemia and proctitis. Further data collection regarding the sexual practices of those with diagnoses of mpox as well as seminal, anorectal, and genital swabbing would be valuable to confirm the mode of transmission and cause of mpox proctitis.
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