Impact of Race and Social Determinants of Health on Outcomes in Patients with Aggressive B-cell nHL Treated with CAR-T.

Healthcare disparities driven by multiple social, economic, and/or environmental factors lead to inequalities in health outcomes. CAR-T cell immunotherapy is an effective therapy for relapsed/refractory B-cell non-Hodgkin lymphoma (r/r B-NHL). However, data are limited on the impact of the convergence of race and social determinants of health on outcomes for patients treated with CAR-T therapy. We examined the impact of interactions between race and insurance type on health care utilization and outcomes in patients treated with CAR-T for aggressive B-NHL. Adult patients with r/r B-NHL treated with CD19 CAR-T were identified between 2015 and 2021 across 13 US academic centers. Insurance type, demographic and clinical data were collected and analyzed via Chi-squared and Kaplan-Meier analysis. Cox multivariable regression (MVA) was used to determine the impact of race/ethnicity and other variables on survival. 466 adult patients were included in our analysis. Median follow-up after CAR-T was 12.7 months. Median progression free survival (mPFS) was longer for Caucasians (11.5 months) than for African Americans (3.5 months, HR 1.56 [1.03-2.4], p=0.04) or Asians (2.7 months, HR 1.7 [1.02-2.67], p=0.04). Differences in median overall survival (mOS) were not significant. For Medicare (n=206) vs Medicaid (n=33) vs private insurance (n=219) vs self-pay (n=7): mPFS was 15.9 vs 4.2 vs 6.0 vs 0.9 months (p<0.001) and mOS was 31.2 vs 12.8 vs 21.5 vs 3.2 months (p<0.001), respectively. Collectively, our multi-center retrospective analysis showed that race and insurance status can impact outcomes for patients treated with CAR-T cell therapy.

Peri-CAR-T practice patterns and survival predictors for all CAR-T patients and post-CAR-T failure in aggressive B-NHL.

Most patients receiving chimeric antigen receptor T-cell therapy (CAR-T) for aggressive B-cell non-Hodgkin lymphoma (B-NHL) do not experience a durable remission. Several novel agents are approved to treat relapsed, refractory aggressive B-NHL; however, it remains unclear how to sequence these therapies pre- and post-CAR-T. We conducted a multicenter retrospective analysis to describe peri-CAR-T practice patterns and survival predictors for patients receiving CD19-directed CAR-T. Patients (n = 514) from 13 centers treated with CAR-T for B-NHL between 2015-2021 were included in the study. Survival curves were constructed using Kaplan-Meier method. Multivariate Cox regression analysis was used to determine the impact of the variables on survival outcomes. For all patients receiving CAR-T, a greater number of lines of therapy pre-CAR-T apheresis and bridging therapy were predictive of inferior progression-free survival (PFS) and overall survival (OS). The median PFS and OS from the time of CAR-T cell infusion were 7.6 and 25.6 months, respectively. From the time of progression post-CAR-T, the median OS was 5.5 months. The median PFS of treatments administered in the first-line post-CAR-T failure was 2.8 months. Patients with refractory disease on day 30 had inferior OS and were less likely to receive subsequent treatment(s) than other patients with CAR-T failure. Allogeneic hematopoietic cell transplantation for selected patients at any time following CAR-T failure led to durable responses in over half of patients at 1 year. These data provide a benchmark for future clinical trials in patients with post-CAR-T cell progression, which remains an unmet clinical need.

Mechanisms of Resistance to Monoclonal Antibodies (mAbs) in Lymphoid Malignancies.

PURPOSE OF REVIEW: Passive immunotherapy with therapeutic monoclonal antibodies (mAbs) has revolutionized the treatment of cancer, especially hematological malignancies over the last 20 years. While use of mAbs has improved outcomes, development of resistance is inevitable in most cases, hindering the long-term survival of cancer patients. This review focuses on the available data on mechanisms of resistance to rituximab and includes some additional information for other mAbs currently in use in hematological malignancies. RECENT FINDINGS: Mechanisms of resistance have been identified that target all described mechanisms of mAb activity including altered antigen expression or binding, impaired complement-mediated cytotoxicity (CMC) or antibody-dependent cellular cytotoxicity (ADCC), altered intracellular signaling effects, and inhibition of direct induction of cell death. Numerous approaches to circumvent identified mechanisms of resistance continue to be investigated, but a thorough understanding of which resistance mechanisms are most clinically relevant is still elusive. In recent years, a deeper understanding of the tumor microenvironment and targeting the apoptotic pathway has led to promising breakthroughs. Resistance may be driven by unique patient-, disease-, and antibody-related factors. Understanding the mechanisms of resistance to mAbs will guide the development of strategies to overcome resistance and re-sensitize cancer cells to these biological agents.

Relativistic spin precession in the double pulsar.

The double pulsar PSR J0737-3039A/B consists of two neutron stars in a highly relativistic orbit that displays a roughly 30-second eclipse when pulsar A passes behind pulsar B. Describing this eclipse of pulsar A as due to absorption occurring in the magnetosphere of pulsar B, we successfully used a simple geometric model to characterize the observed changing eclipse morphology and to measure the relativistic precession of pulsar B's spin axis around the total orbital angular momentum. This provides a test of general relativity and alternative theories of gravity in the strong-field regime. Our measured relativistic spin precession rate of 4.77 degrees (-0 degrees .65)(+0 degrees .66) per year (68% confidence level) is consistent with that predicted by general relativity within an uncertainty of 13%.