Nonspecific Signs and/or Symptoms of Cancer: A Retrospective, Observational Analysis from a Secondary Care, US Community Oncology Dataset.

To help determine the unmet need for improved diagnostic tools to evaluate patients with nonspecific signs and/or symptoms (NSSS) and suspicion of cancer, we examined patient characteristics, diagnostic journey, and cancer incidence of patients with NSSS within The US Oncology Network (The Network), a secondary care community oncology setting. This retrospective, observational cohort study included patients aged ≥40 years with ≥1 NSSS in their problem list at their first visit within The Network (the index date) between 1 January 2016 and 31 December 2020. Patients were followed longitudinally with electronic health record data for initial cancer diagnosis, new noncancer diagnosis, death, end of study observation period, or 12 months, whichever occurred first. Of 103,984 patients eligible for inclusion, 96,722 presented with only 1 NSSS at index date; 6537/103,984 (6.3%) were diagnosed with 1 primary cancer within 12 months after the index date; 3825/6537 (58.5%) with hematologic malignancy, and 2712/6537 (41.5%) with solid tumor. Among patients diagnosed with cancer (n = 6774), the median time to cancer diagnosis after their first visit within The Network was 5.13 weeks. This study provides a real-world perspective on cancer incidence in patients with NSSS referred to a secondary care setting and highlights the unmet need for improved diagnostic tools to improve cancer outcomes.

Hemorrhagic Cystitis Secondary to Adenovirus and BK Virus Infection in a Diffuse Large B-Cell Lymphoma Patient with Recent CAR T-Cell Therapy.

Patients who undergo chimeric antigen receptor T-cell therapy (CAR T-cell therapy) are immunosuppressed due to multiple factors. While adenovirus and BK virus are well-known pathogens in the context of hematopoietic stem cell transplant, there are no detailed reports of these infections in the setting of CAR T-cell therapy. We describe a 70-year-old male who recently underwent CAR T-cell therapy for diffuse large B-cell lymphoma. He presented with intractable gross hematuria and dysuria. Workup revealed adenovirus viremia and viruria and BK virus viruria. He was treated for adenovirus hemorrhagic cystitis with intravenous cidofovir 1 mg/kg/day, every three days for three weeks, with good clinical response. We also discuss the mechanisms of immunosuppression in CAR T-cell therapy as well as the principles of treatment of adenovirus and BK virus infections in the immunosuppressed patient.

A Phase I/II Study of Evofosfamide, A Hypoxia-activated Prodrug with or without Bortezomib in Subjects with Relapsed/Refractory Multiple Myeloma.

PURPOSE: The presence of hypoxia in the diseased bone marrow presents a new therapeutic target for multiple myeloma. Evofosfamide (formerly TH-302) is a 2-nitroimidazole prodrug of the DNA alkylator, bromo-isophosphoramide mustard, which is selectively activated under hypoxia. This trial was designed as a phase I/II study investigating evofosfamide in combination with dexamethasone, and in combination with bortezomib and dexamethasone in relapsed/refractory multiple myeloma. PATIENTS AND METHODS: Fifty-nine patients initiated therapy, 31 received the combination of evofosfamide and dexamethasone, and 28 received the combination of evofosfamide, bortezomib, and dexamethasone. Patients were heavily pretreated with a median number of prior therapies of 7 (range: 2-15). All had previously received bortezomib and immunomodulators. The MTD, treatment toxicity, and efficacy were determined. RESULTS: The MTD was established at 340 mg/m2 evofosfamide + dexamethasone with dose-limiting mucositis at higher doses. For the combination of evofosfamide, bortezomib, and dexamethasone, no patient had a dose-limiting toxicity (DLT) and the recommended phase II dose was established at 340 mg/m2. The most common ≥grade 3 adverse events (AE) were thrombocytopenia (25 patients), anemia (24 patients), neutropenia (15 patients), and leukopenia (9 patients). Skin toxicity was reported in 42 (71%) patients. Responses included 1 very good partial response (VGPR), 3 partial response (PR), 2 minor response (MR), 20 stable disease (SD), and 4 progressive disease (PD) for evofosfamide + dexamethasone and 1 complete response (CR), 2 PR, 1 MR, 18 SD, and 5 PD for evofosfamide + bortezomib + dexamethasone. Disease stabilization was observed in over 80% and this was reflective of the prolonged overall survival of 11.2 months. CONCLUSIONS: Evofosfamide can be administered at 340 mg/m2 twice a week with or without bortezomib. Clinical activity has been noted in patients with heavily pretreated relapsed refractory multiple myeloma.