Five-Year Follow-Up of Standard-of-Care Axicabtagene Ciloleucel for Large B-Cell Lymphoma: Results From the US Lymphoma CAR T Consortium.

Purpose: Axicabtagene ciloleucel (axi-cel) is an autologous CD19 chimeric antigen receptor (CAR) T-cell therapy that is approved for the treatment of relapsed or refractory large B-cell lymphoma. Little is known about the long-term survivorship after CAR T-cell therapy.

Methods: We previously reported the results of 298 patients who were leukapheresed with the intent to receive standard-of-care axi-cel (n = 275 infused) after two or more previous lines of therapy at a median follow-up of 12.

Outcomes of patients with R/R B-cell NHL and limited (<5 sites) pre-CART disease bridged with or without radiotherapy.

Unirradiated patients with relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (NHL) who undergo anti-CD19 chimeric antigen receptor T-cell therapy (CART) have a predominant localized pattern of relapse, the significance of which is heightened in individuals with limited/localized disease before CART. This study reports on the outcomes of patients with R/R NHL and limited (<5 involved sites) disease bridged with or without radiotherapy. A multicenter retrospective review of 150 patients with R/R NHL who received CART with <5 disease sites before leukapheresis was performed.

High-performance Ge-on-insulator lateral p-i-n waveguide photodetectors for electronic-photonic integrated circuits at telecommunication wavelengths.

We report high-performance germanium-on-insulator (GeOI) waveguide photodetectors (WGPDs) for electronic-photonic integrated circuits (EPICs) operating at telecommunication wavelengths. The GeOI samples were fabricated using layer transfer and wafer-bonding techniques, and a high-quality Ge active layer was achieved. Planar lateral p-i-n WGPDs were fabricated and characterized, and they exhibited a low dark current of 0.

Serial Evaluation of Preimmunization Antibody Titers in Lymphoma Patients Receiving Chimeric Antigen Receptor T Cell Therapy.

Antibody titers and the potential need for immunization have not been formally studied in recipients of chimeric antigen receptor T cell therapy (CAR-T). Prior studies have shown that CD19-targeted CAR-T can induce persistent B cell aplasia but preserve plasma cells for humoral response. Aiming to assess the immune repertoire and antibody titer status of CAR-T recipients, we conducted a retrospective study of immune cell recovery and antibody titers to vaccines in anti-CD19 CAR-T recipients at Mayo Clinic, Rochester.

The CAR-HEMATOTOX score as a prognostic model of toxicity and response in patients receiving BCMA-directed CAR-T for relapsed/refractory multiple myeloma.

Background: BCMA-directed CAR T-cell therapy (CAR-T) has altered the treatment landscape of relapsed/refractory (r/r) multiple myeloma, but is hampered by unique side effects that can lengthen hospital stays and increase morbidity. Hematological toxicity (e.g.

Consolidative radiotherapy for residual fluorodeoxyglucose activity on day +30 post CAR T-cell therapy in non-Hodgkin lymphoma.

Majority of non-Hodgkin lymphoma (NHL) patients who achieve partial response (PR) or stable disease (SD) to CAR T-cell therapy (CAR T) on day +30 progress and only 30% achieve spontaneous complete response (CR). This study is the first to evaluate the role of consolidative radiotherapy (cRT) for residual fluorodeoxyglucose (FDG) activity on day +30 post- CAR T in NHL. We retrospectively reviewed 61 patients with NHL who received CAR T and achieved PR or SD on day +30.

Efficacy of checkpoint inhibition after CAR-T failure in aggressive B-cell lymphomas: outcomes from 15 US institutions.

Checkpoint inhibitor (CPI) therapy with anti-PD-1 antibodies has been associated with mixed outcomes in small cohorts of patients with relapsed aggressive B-cell lymphomas after CAR-T failure. To define CPI therapy efficacy more definitively in this population, we retrospectively evaluated clinical outcomes in a large cohort of 96 patients with aggressive B-cell lymphomas receiving CPI therapy after CAR-T failure across 15 US academic centers. Most patients (53%) had diffuse large B-cell lymphoma, were treated with axicabtagene ciloleucel (53%), relapsed early (≤180 days) after CAR-T (83%), and received pembrolizumab (49%) or nivolumab (43%).

Prognostic value of early bone marrow MRD status in CAR-T therapy for myeloma.

Bone marrow (BM) assessment of minimal residual disease (MRD) is prognostic for survival in multiple myeloma (MM). BM is still hypocellular at month 1 post CAR-T, thus the value of MRD negative (MRDneg) status at this timepoint is unclear. We examined the impact of month 1 BM MRD status in MM patients who received CART at Mayo Clinic between 8/2016 and 6/2021.

Response to COVID-19 Vaccination Post-CAR T Therapy in Patients With Non-Hodgkin Lymphoma and Multiple Myeloma.

COVID-19 adversely affects individuals with cancer. Several studies have found that seroconversion rates among patients with hematologic malignancies are suboptimal when compared to patients without cancer. Patients with non-Hodgkin lymphoma (NHL) and multiple myeloma (MM) are immunocompromised due to impaired humoral and cellular immunity in addition to prescribed immunosuppressive therapy.

Procalcitonin as a biomarker for predicting bacterial infection in chimeric antigen receptor T-cell therapy recipients.

Background: It is unknown whether serum procalcitonin (PCT) concentration monitoring can differentiate between bacterial infection or cytokine release syndrome (CRS) when chimeric antigen receptor T-cell (CAR-T) recipients present with a constellation of signs and symptoms that may represent both complications.

Objective: The objective of the study was to assess the utility of serum PCT concentrations as a biomarker of bacterial infection in CAR-T recipients.

Study Design: This single-center, retrospective, medical record review evaluated patients prescribed CAR-T therapy until death or 30 days after infusion.

Don't Put the CART Before the Horse: The Role of Radiation Therapy in Peri-CAR T-cell Therapy for Aggressive B-cell Non-Hodgkin Lymphoma.

Purpose: The optimal approach to incorporate radiation therapy (RT) in conjunction with chimeric antigen receptor (CAR) T-cell therapy (CART) for relapsed/refractory (r/r) B-cell non-Hodgkin lymphoma (bNHL) remains unclear. This study documented the RT local control rate among patients who received bridging radiation therapy (BRT) before CART and compares it with those who received salvage radiation therapy (SRT) after CART. This article further reports on a promising way to use SRT for post-CART disease and identifies predictors for RT in-field recurrence.

Uncertainty-informed deep learning models enable high-confidence predictions for digital histopathology.

A model's ability to express its own predictive uncertainty is an essential attribute for maintaining clinical user confidence as computational biomarkers are deployed into real-world medical settings. In the domain of cancer digital histopathology, we describe a clinically-oriented approach to uncertainty quantification for whole-slide images, estimating uncertainty using dropout and calculating thresholds on training data to establish cutoffs for low- and high-confidence predictions. We train models to identify lung adenocarcinoma vs.

Impact of Rituximab and Corticosteroids on Late Cytopenias Post-Chimeric Antigen Receptor T Cell Therapy.

Chimeric antigen receptor (CAR) T cell therapy represents a significant advancement in the treatment of patients with relapsed/refractory B cell lymphoid malignancies. Cytokine release syndrome and immune effector cell-associated neurotoxicity represent the most acute serious adverse events post CAR T cell therapy but the occurrence and persistence of cytopenias post CAR T cell therapy represent a significant adverse event and a management challenge. While most patients typically recover blood counts by 30 days, a significant subset of patients have persistent or late cytopenias beyond 30 days.

Incidence and Risk Factors for Acute Kidney Injury After Chimeric Antigen Receptor T-Cell Therapy.

Objective: To evaluate the association of baseline and postinfusion patient characteristics with acute kidney injury (AKI) in the month after chimeric antigen receptor T-cell (CAR-T) therapy.

Methods: We retrospectively reviewed records of 83 patients with non-Hodgkin lymphoma undergoing CAR-T therapy (axicabtagene ciloleucel) between June 2016 and November 2020. Patients were followed up to 1 month after treatment.