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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.

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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.

No abstract

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2543 Background: Although chimeric antigen receptor (CAR)-T cells produce impressive outcomes in B-cell malignancies, a substantial fraction of patients with relapsed/refractory B-cell leukemia and lymphoma treated with anti-CD19 CAR-T cell therapy (CART19) either do not respond to treatment or relapse, with poor CAR-T cell persistence or CD19 antigen escape being two key factors that limit durability of response. In order to address these factors, we initiated a clinical trial with naïve/memory T (TN/MEM) cells engineered to express bispecific anti-CD19/CD20 CARs (CART19/20) (NCT04007029). Methods: This trial is a Phase 1, first-in-human, dose-escalation trial enrolling patients with relapsed or refractory follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), mantle-cell lymphoma (MCL) and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Following lymphodepletion chemotherapy with fludarabine and cyclophosphamide, patients received CART19/20 cell doses ranging from 50 x 106 to 200 x 106 CAR-positive cells. The primary endpoint was to evaluate the safety of CART19/20 as measured by adverse events and dose limiting toxicities. Secondary endpoints were efficacy as assessed by disease response, progression-free survival (PFS), overall survival (OS), and CAR transgene persistence. Results: As of February 7, 2022, dose-escalation has been completed with 9 patients enrolled and 8 patients infused (3 FL, 4 DLBCL including 2 transformed follicular and 1 primary mediastinal B cell, and 1 MCL). with CART19/20 cells on this study. The median age at the time of CART19/20 infusion was 59 and median prior lines of therapy was 3.5. All patients had stage IV disease and 7 of 9 patients required bridging therapy. Grade-1 cytokine release syndrome (CRS) occurred in 6 of 8 patients, and no patient experienced immune effector cell-associated neurotoxicity syndrome ( ICANS). Among all patients, only one dose of tocilizumab was administered to one subject, and no steroids were given. With a median follow-up of 12 months from time of CART19/20 infusion (range: 4+ to 24+ months), 7 of 8 of patients remain in a complete remission. Median PFS and OS were not reached, and all patients with a complete remission demonstrate ongoing B-cell aplasia. Conclusions: This study demonstrates that CART19/20 cells are safe and effective in patients with relapsed/refractory NHL and potentially obviates the challenges of the commonest causes of relapse after CAR-T cell therapy by means of modifying TN/MEM cells and dual-antigen targeting, respectively. Given the strong safety and response observed, dose escalation was completed with the second dosing level (DL2) of 200 x 106 CAR-positive cells, and DL1 of 50 x 106 CAR-positive cells was chosen as the therapeutic dose for future trial expansion. Clinical trial information: NCT04007029.