CD19/CD20 Bispecific Chimeric Antigen Receptor (CAR) in Naive/Memory T Cells for the Treatment of Relapsed or Refractory Non-Hodgkin Lymphoma.

To address antigen escape and loss of T-cell functionality, we report a phase I clinical trial (NCT04007029) evaluating autologous naive and memory T (TN/MEM) cells engineered to express a bispecific anti-CD19/CD20 chimeric antigen receptor (CAR; CART19/20) for patients with relapsed/refractory non-Hodgkin lymphoma (NHL), with safety as the primary endpoint. Ten patients were treated with 36 × 106 to 165 × 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 10 patients achieved objective response [90% overall response rate (ORR)], with seven achieving complete remission [70% complete responses (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 was 18 months and median overall survival was 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. SIGNIFICANCE: Autologous CD19/CD20 bispecific CAR-T cell therapy generated from TN/MEM cells for patients with NHL is safe (no neurotoxicity, maximum grade 1 cytokine release syndrome) and demonstrates strong efficacy (90% ORR, 70% CR rate) in a first-in-human, phase I dose-escalation trial. This article is highlighted in the In This Issue feature, p. 517.

Chemotherapy regimen choice and patient outcomes in early-stage triple-negative breast cancer: a retrospective analysis.

Background: Triple-negative breast cancer (TNBC) is associated with a poor prognosis when compared to hormone receptor-positive breast cancers. Anthracycline-based regimens (ABRs) are mainstay for treatment of non-metastatic TNBC. However, anthracyclines are associated with an increased risk of potentially life-threatening adverse effects. We sought to evaluate outcomes in patients with early TNBC treated with ABRs versus those treated with anthracycline-sparing regimens (ASRs). Methods: All patients treated for stage I-III TNBC who had undergone curative-intent surgery at a large academic medical center between January 2013 and May 2018 were included in this retrospective study. Event-free survival (EFS) and disease-free survival (DFS) were the primary endpoints, with overall survival (OS) as a secondary endpoint and were defined as per standardized STEEP criteria. Kaplan-Meier, multivariable Cox regression, and log-rank tests were used to define key survival and treatment-related differences between subjects treated with ABRs versus ASRs. Results: One hundred thirty-two patients met inclusion criteria with a median follow-up of 55.9 months. Twenty-seven patients (20%) had disease recurrence and 20 (15%) died. Patients in the ABR group were more likely to have nodal involvement (chi-square p = 0.011). Patients treated with ABRs (n = 26, 20%) compared with ASRs (n = 106, 80%) had significantly shorter median EFS (32.4 months vs not reached (NR), p < 0.001), DFS (26.2 months vs NR, p < 0.001), and OS (49.2 months vs NR, p < 0.001). The shorter survival observed in the ABR group persisted after adjusting for nodal status and on multivariate analysis. Of the 26 ABR-treated patients, 9 (35%) had an anthracycline added after suboptimal response to an ASR. Regardless of reason for anthracycline inclusion, the survival outcomes were similar. No cardiac or secondary leukemic events were observed in either group. Conclusion: ABRs were associated with shorter EFS, DFS, and OS, even after adjusting for certain high-risk clinical features.

Treating Penile Cancer in the Immunotherapy and Targeted Therapy Era.

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.