To address antigen escape and loss of T-cell functionality, we report a phase-1 clinical trial (NCT04007029) evaluating autologous naive and memory T (TN/MEM) cells engineered to express a bispecific anti-CD19/CD20 CAR (CART19/20) for patients with relapsed/refractory NHL, with safety as the primary end point. Ten patients were treated with 36–165 x 106 CART19/20 cells. No patient experienced neurotoxicity of any grade, or over grade-1 cytokine release syndrome. One case of dose-limiting toxicity (persistent cytopenia) was observed. Nine of ten patients achieved objective response (90% ORR), with seven achieving complete remission (70% CR rate). One patient relapsed after 18 months in CR, but returned to CR after receiving a second dose of CART19/20 cells. Median progression-free survival and overall survival were not reached with a 17-month median follow-up. In conclusion, CART19/20 TN/MEM cells are safe and effective in patients with relapsed/refractory NHL, with durable responses achieved at low dosage levels.
While localized penile cancers are typically treated surgically and metastatic penile cancers benefit from standard chemotherapy, there have been studies on the horizon demonstrating immunotherapy as a novel approach to metastatic penile cancers that have failed standard chemotherapy. We report a case series of two patients who improved on immunotherapy after progressing with standard chemotherapy regimens. The first case describes a 64-year-old male with a penile mass and significant lymphadenopathy who had surgical resection and adjuvant chemotherapy prior to continued disease progression. He was started on anti-EGFR treatment and improved initially, but he eventually had progression of disease. The second case describes a 79-year-old male with a penile mass who was treated with surgical resection and started on adjuvant chemoradiation, but he developed recurrence and nodal involvement. Therefore, second-line therapy of the PD-L1 inhibitor was started in this patient. There were no available clinical trials for penile cancer patients who progressed beyond the standard surgical therapy and chemotherapy.
Kaposi's sarcoma and multicentric Castleman Disease are HIV-related disease processes that are associated with human herpesvirus 8 (HHV-8) infection. The development of multicentric Castleman disease can often be a manifestation of the immune reconstitution inflammatory syndrome phenomenon and is associated with markedly elevated levels of HHV-8 viremia, as illustrated by this case.
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