Anisotropic Foams via Frontal Polymerization.

The properties of foams, an important class of cellular solids, are most sensitive to the volume fraction and openness of its elementary compartments; size, shape, orientation, and the interconnectedness of the cells are other important design attributes. Control of these morphological traits would allow the tailored fabrication of useful materials. While approaches like ice templating have produced foams with elongated cells, there is a need for rapid, versatile, and energy-efficient methods that also control the local order and macroscopic alignment of cellular elements. Here, a fast and convenient method is described to obtain anisotropic structural foams using frontal polymerization. Foams are fabricated by curing mixtures of dicyclopentadiene and a blowing agent via frontal ring-opening metathesis polymerization (FROMP). The materials are characterized using microcomputed tomography (micro-CT) and an image analysis protocol to quantify the morphological characteristics. The cellular structure, porosity, and hardness of the foams change with blowing agent, concentration, and resin viscosity. Moreover, a full factorial combination of variables is used to correlate each parameter with the structure of the obtained foams. The results demonstrate the controlled production of foams with specific morphologies using the simple and efficient method of frontal polymerization.

Axicabtagene Ciloleucel in the Non-Trial Setting: Outcomes and Correlates of Response, Resistance, and Toxicity.

PURPOSE: Axicabtagene ciloleucel (axi-cel) was approved by the Food and Drug Administration for relapsed aggressive B-cell non-Hodgkin lymphoma in part on the basis of durable remission rates of approximately 40% in a clinical trial population. Whether this efficacy, and the rates of toxicity, would be consistent in a postcommercial setting, with relaxed eligibility criteria and bridging therapy, is unknown. This study describes the efficacy and safety correlates and outcomes in this setting. PATIENTS AND METHODS: One hundred twenty-two patients from 7 medical centers in the United States were treated with axi-cel and were included in a modified intent-to-treat (mITT) analysis. Seventy-six patients (62%) were ineligible for the ZUMA-1 trial. Response and toxicity rates, duration of response (DOR), survival, and covariates are described on the basis of the mITT population. Correlative studies on blood and tumor samples were performed to investigate potential biomarkers of response and resistance. RESULTS: Median follow-up was 10.4 months. In the mITT population, the best overall and complete response (CR) rates were 70% and 50%, respectively. Median DOR and progression-free survival (PFS) were 11.0 and 4.5 months in all patients and were not reached (NR) in CR patients. Median overall survival (OS) was NR; 1-year OS was 67% (95% CI, 59% to 77%). Although response rates were similar in the ZUMA-1-eligible and ZUMA-1-ineligible groups (70% v 68%), there was a statistically significant improvement in CR rate (63% v 42%, P = .016), DOR (median, NR v 5.0 months; P = .014), PFS (median, NR v 3.3 months; P = .020), and OS (1-year OS, 89% v 54%; P < .001) in patients who were ZUMA-1 eligible. Rates of grade ≥ 3 cytokine release syndrome and neurotoxicty were 16% and 35%, respectively. CONCLUSION: Axi-cel yields similar rates of overall response and toxicity in commercial and trial settings, although CR rates and DOR were more favorable in patients eligible for ZUMA-1.

Chimeric antigen receptor T-cell therapy for the treatment of aggressive B-cell non-Hodgkin lymphomas: efficacy, toxicity, and comparative chimeric antigen receptor products.

Introduction: Traditionally, outcomes for patients with relapsed/refractory aggressive B-cell non-Hodgkin lymphoma have been poor. There has been a clear need for effective therapeutic options that could produce durable remissions with a reasonable safety profile. The approval of chimeric antigen receptor (CAR) T-cell therapies has been revolutionary in the field because CAR T-cells meet this need for a substantial number of patients. With multiple approved CAR T-cell products and more expected soon, it can be difficult to distinguish between the various products and decide which to use. Effective CAR T-cell therapeutic choice is enhanced by an understanding of the biology of CAR T-cell, as well as the mechanisms associated with both efficacy and toxicity. Areas Covered: Biology of CAR T-cells, as well as a discussion of their efficacy and toxicity. Mechanisms of resistance, current unanswered questions in the field, issues associated with choosing a CAR T-cell product, and future directions for the advancement of CAR T-cell therapy. Expert Opinion: Due to differences in study populations and manufacturing times, it is too early to know if there is a 'best' choice for CAR T-cell therapy. Decisions must be individualized taking into account patient factors and expected toxicity.