Influence of Income, Education, and Medicaid Expansion on Palliative Care in Acute Myeloid Leukemia Using the National Cancer Database.

Palliative care is integral to symptom management, and we examined its relationship with income, education, and Medicaid expansion in acute myeloid leukemia. This was a retrospective cross-sectional study using the National Cancer Database that included patients with acute myeloid and monocytic leukemias > 18 years of age treated at Commission on Cancer facilities from 2004 to 2016. Univariate and multivariate models were adjusted for demographic variables and facility characteristics. There were 124,988 patients, but only 106,495 had palliative care data, and of this 4111 (3%) received palliative care. The most educated had the highest odds of receiving palliative care (odds ratio, OR 1.23, 95% CI 1.08-1.41; P = 0.002), but the highest income bracket (≥ $63,333) had the lowest odds (OR 0.82, 95% CI 0.72-0.93; P = 0.003). Residence in states with Medicaid expansion (January 2014 onward) had greater palliative care utilization. Palliative care use was associated with higher education but underutilized with higher incomes. Increased access with Medicaid expansion suggests the importance of public insurance.

Hospital facility characteristics and socioeconomic factors on outcomes and treatment in patients with multiple myeloma: National Cancer Database analysis.

Previous studies have shown that socioeconomic factors play an important role in multiple myeloma (MM) health outcomes. We postulated that the type of treatment facilities and their volume of cases also affect overall survival, utilization of various therapies including palliative care services in newly diagnosed MM. Using the National Cancer Database (NCDB), we analyzed 174,551 newly diagnosed MM participants from across the country. We found that at high volume facility centers (over 90th percentile of new patient volume from 2004 to 2016), the median overall survival (OS) was 62.3 months versus 35.3 months at lower volume facilities (p <0.001). Similarly, high volume academic cancer centers had an improved median OS of 66.4 months (65.3-67.4 CI) versus 39.2 months (37.9-40.4 months CI) in lower volume academic centers (p <0.001). The odds of utilizing chemotherapy, immunotherapy, and autologous transplants were higher in academic cancer centers compared to community cancer centers, after adjusting for demographic and socioeconomic factors (OR 1.10, 1.23, and 2.06 respectively, all with p<0.001). There was significantly decreased odds of receiving palliative care (OR 0.89, 95% CI 0.85-0.93) in high volume facilities compared to low volume. Palliative care services were more frequently utilized at integrated network cancers and comprehensive community cancer centers compared to community cancer centers, with similar odds of receiving palliative care between community and academic facility types. Our results likely reflect increased provider experience and resources in higher volume and academic facilities. This highlights the need to integrate resources and improve access to community programs.

Rational design of a trimeric APRIL-based CAR-binding domain enables efficient targeting of multiple myeloma.

Chimeric antigen receptor (CAR) T cells (CARTs) have shown tremendous potential for the treatment of certain B-cell malignancies, including patients with relapsed/refractory multiple myeloma (MM). Targeting the B-cell maturation antigen (BCMA) has produced the most promising results for CART therapy of MM to date, but not all remissions are sustained. Emergence of BCMA escape variants has been reported under the selective pressure of monospecific anti-BCMA CART treatment. Thus, there is a clinical need for continuous improvement of CART therapies for MM. Here, we show that a novel trimeric APRIL (a proliferation-inducing ligand)-based CAR efficiently targets both BCMA+ and BCMA- MM. Modeled after the natural ligand-receptor pair, APRIL-based CARs allow for bispecific targeting of the MM-associated antigens BCMA and transmembrane activator and CAML interactor (TACI). However, natural ligands as CAR antigen-binding domains may require further engineering to promote optimal binding and multimerization to adequately trigger T-cell activation. We found that using a trimeric rather than a monomeric APRIL format as the antigen-binding domain enhanced binding to BCMA and TACI and CART activity against MM in vitro and in vivo. Dual-specific, trimeric APRIL-based CAR are a promising therapeutic approach for MM with potential for preventing and treating BCMA escape.