Low booster uptake in cancer patients despite health benefits.

Patients with cancer are at increased risk of death from COVID-19 and have reduced immune responses to SARS-CoV2 vaccines, necessitating regular boosters. We performed comprehensive chart reviews, surveys of patients attitudes, serology for SARS-CoV-2 antibodies and T-cell receptor (TCR) ß sequencing for cellular responses on a cohort of 982 cancer patients receiving active cancer therapy accrued between November-3-2020 and Mar-31-2023. We found that 92·3% of patients received the primer vaccine, 70·8% received one monovalent booster, but only 30·1% received a bivalent booster. Booster uptake was lower under age 50, and among African American or Hispanic patients. Nearly all patients seroconverted after 2+ booster vaccinations (>99%) and improved cellular responses, demonstrating that repeated boosters could overcome poor response to vaccination. Receipt of booster vaccinations was associated with a lower risk of all-cause mortality (HR=0·61, P=0·024). Booster uptake in high-risk cancer patients remains low and strategies to encourage booster uptake are needed. Highlights: COVID-19 booster vaccinations increase antibody levels and maintain T-cell responses against SARS-CoV-2 in patients receiving various anti-cancer therapiesBooster vaccinations reduced all-cause mortality in patientsA significant proportion of patients remain unboosted and strategies are needed to encourage patients to be up-to-date with vaccinations.

Autologous stem cell transplantation after anti-PD-1 therapy for multiply relapsed or refractory Hodgkin lymphoma.

Autologous stem cell transplantation (ASCT) can be curative for patients with relapsed/refractory Hodgkin lymphoma (HL). Based on studies suggesting that anti-PD-1 monoclonal antibodies (mAbs) can sensitize patients to subsequent chemotherapy, we hypothesized that anti-PD-1 therapy before ASCT would result in acceptable outcomes among high-risk patients who progressed on or responded insufficiently to ≥1 salvage regimen, including chemorefractory patients who are traditionally considered poor ASCT candidates. We retrospectively identified 78 HL patients who underwent ASCT after receiving an anti-PD-1 mAb (alone or in combination) as third-line or later therapy across 22 centers. Chemorefractory disease was common, including 42 patients (54%) refractory to ≥2 consecutive systemic therapies immediately before anti-PD-1 treatment. Fifty-eight (74%) patients underwent ASCT after anti-PD-1 treatment, while 20 patients (26%) received additional therapy after PD-1 blockade and before ASCT. Patients received a median of 4 systemic therapies (range, 3-7) before ASCT, and 31 patients (41%) had a positive pre-ASCT positron emission tomography (PET) result. After a median post-ASCT follow-up of 19.6 months, the 18-month progression-free survival (PFS) and overall survival were 81% (95% CI, 69-89) and 96% (95% confidence interval [CI], 87-99), respectively. Favorable outcomes were observed for patients who were refractory to 2 consecutive therapies immediately before PD-1 blockade (18-month PFS, 78%), had a positive pre-ASCT PET (18-month PFS, 75%), or received ≥4 systemic therapies before ASCT (18-month PFS, 73%), while PD-1 nonresponders had inferior outcomes (18-month PFS, 51%). In this high-risk cohort, ASCT after anti-PD-1 therapy was associated with excellent outcomes, even among heavily pretreated, previously chemorefractory patients.

Updates on Circulating Tumor DNA Assessment in Lymphoma.

PURPOSE OF REVIEW: The use of circulating tumor DNA (ctDNA) for the purposes of diagnosis, prognosis, assessment of treatment response, and monitoring for relapse is a new and developing field in lymphoma. This review aims to summarize many of the most recent advances in ctDNA applications. RECENT FINDINGS: Recent studies have demonstrated the use of ctDNA assessment across many lymphoma subtypes including diffuse large B-cell lymphoma, follicular lymphoma, Hodgkin lymphoma, and T-cell lymphoma. In addition, many novel applications of ctDNA assessment have been described such as the development of new prognostic models, investigation of clonal evolution and heterogeneity, early assessment of treatment response, and prediction of response to targeted therapy as a form of personalized medicine. The use of ctDNA has been shown to be feasible across many lymphoma subtypes and has shown significant promise for several new applications. Additional studies will be needed to validate these findings prior to routine use in clinical practice.

Interaction of N-methyl-D-aspartate and group 5 metabotropic glutamate receptors on behavioral flexibility using a novel operant set-shift paradigm.

Behavioral flexibility or 'set-shifting' refers to the ability to modify ongoing behavior in response to changing goals or environmental contingencies. Impaired behavioral flexibility is associated with disorders such as schizophrenia and addiction. Hypofunction of N-methyl-D-aspartate (NMDA) receptors has been implicated in these impairments. Metabotropic glutamate 5 (mGlu5) receptors closely interact with NMDA receptors and may provide a feasible pharmacological target for indirect manipulation of NMDA receptor function in disease states. The aim of this study was to examine the impact of NMDA and mGlu5 receptors on set-shifting ability. We developed a computer-controlled, operant-based set-shifting task that requires rats to learn sequential discrimination rules based on two distinct perceptual dimensions. Using this task, we found that administration of the NMDA receptor antagonist MK801, both systemically and intracortically, significantly impaired task performance, whereas stimulation or inhibition of mGlu5 receptors did not impair task performance. However, when administered after MK801, potentiation of mGlu5 receptor function reduced the performance impairments observed with MK801 alone. These results suggest an interaction between NMDA and mGlu5 receptors in cognitive flexibility and may provide a novel therapeutic approach for treating disorders associated with aberrant NMDA function.