The pace of innovation of multiple myeloma therapy in recent years is remarkable with the advent of monoclonal antibodies and the approval of novel agents with new mechanisms of action. Emerging ...therapies are on the horizon for clinical approval with significant implications in extending patient survival and advancing closer to the goal of a cure, especially in areas of immunotherapy such as chimeric antigen receptor T cells, bispecific T cell engager antibodies, antibody drug conjugates, newer generations of monoclonal antibodies, and small molecule inhibitor and modulators. This review provides an update of current myeloma therapeutics in active preclinical and early clinical development and discusses the mechanism of action of several classes of novel therapeutics. Keywords: Multiple myeloma, Review, First in human trials, Chimeric antigen receptor, CAR-T, Bispecific antibody, T cell engager, Antibody-drug conjugate, Monoclonal antibody, Small molecule inhibitor, Targeted therapy
Financial toxicity, the cumulative financial hardships resulting from cancer diagnosis and treatment, is a growing problem in the United States. With the proliferation of costly novel therapeutics ...and improved cancer survival, financial toxicity will remain a major issue in cancer care delivery. Frontline oncology providers serve as gatekeepers in the medical system and, as such, could play essential roles in recognizing and addressing financial toxicity. Providers and health systems could help mitigate financial toxicity through routine financial toxicity screening, financial navigation, and advocacy. Specific strategies include developing and implementing financial screening instruments that can be integrated in electronic medical records and establishing team-based financial navigation programs to help patients with out-of-pocket medical costs, nonmedical spending, and insurance optimization. Finally, providers should continue to advocate for policies and legislation that decrease cost and promote value-based care. In this review, we examine opportunities for provider engagement in these areas and highlight gaps for future research.
Bacillus species, such as Bacillus subtilis and Bacillus licheniformis, are important industrial bacteria. However, there is a lack of standardized and predictable genetic tools for convenient and ...reproducible assembly of genetic modules in Bacillus species to realize their full potential. In this study, we constructed a Ribosome Binding Site (RBS) library in B. licheniformis, which provides incremental regulation of expression levels over a 10
-fold range. Additionally, we developed a model to quantify the resulting translation rates. We successfully demonstrated the robust expression of various target genes using the RBS library and showed that the model accurately predicts the translation rates of arbitrary coding genes. Importantly, we also extended the use of the RBS library and prediction model to B. subtilis, B. thuringiensis, and B. amyloliquefacie. The versatility of the RBS library and its prediction model enables quantification of biological behavior, facilitating reliable forward engineering of gene expression.
Introduction: Important differences exist between the presentation, treatment, and survivorship of patients and survivors with blood cancers. Furthermore, existing research in financial toxicity has ...not fully addressed the relationship between medical care utilization and patient-reported outcomes of financial barriers and distress. We answered these questions by using a nationally representative survey. Methods: Respondents with blood cancers and solid tumors from the National Health Interview Survey were identified (2014−2020). We identified 23 survey questions as study outcomes and grouped them into three domains of medical care utilization, financial barriers to care, and financial distress. Associations between the three domains and associations of study outcomes between cancer types were examined using weighted univariate analyses and multivariable linear and logistic regressions. Results: The final study group consisted of 6248 respondents with solid tumors and 398 with blood cancers (diagnosed ≤ 5 years). Across all respondents with cancer, higher medical care utilization is generally associated with increased financial barriers to care. Compared to respondents with solid tumors, respondents with blood cancers had a higher level of medical care utilization (β = 0.36, p = 0.02), a lower level of financial barriers to care (β = −0.19, p < 0.0001), and a higher level of financial distress in affording care (β = 0.64, p = 0.03). Conclusions: Patients and survivors with blood cancers and solid tumors demonstrate divergent patterns in care utilization, financial barriers, and financial distress. Future research and interventions on financial toxicity should be tailored for individual cancer groups, recognizing the differences in medical care utilization, which affect the experienced financial barriers.
The concept of time toxicity in oncology refers to the presence of frequent healthcare-related interactions that can interfere with patient well-being. In this review, we examine several ...manifestations of time toxicity in non-Hodgkin lymphoma and multiple myeloma and discuss their impact on decision-making with patients. For example, time toxicity may influence the choice of chemoimmunotherapy versus lenalidomide-rituximab in follicular lymphoma. In myeloma, it may inform the optimal dosing schedule for proteasome inhibitors and bisphosphonates. In both malignancies, varying time toxicity profiles are a key distinction between chimeric antigen receptor T-cell therapies and bispecific antibodies. We outline the challenges with measuring time toxicity as a trial endpoint but discuss its importance as a consideration for patient care, both in standard-of-care settings and in clinical trials. Throughout the review, we highlight strategies to lower the time toxicity of therapies in lymphoma and myeloma without compromising their efficacy or patient safety.
Background
Enfortumab vedotin (EV) is a novel antibody‐drug conjugate approved for advanced urothelial cancer (aUC) refractory to prior therapy. In the Urothelial Cancer Network to Investigate ...Therapeutic Experiences (UNITE) study, the authors looked at the experience with EV in patient subsets of interest for which activity had not been well defined in clinical trials.
Methods
UNITE was a retrospective study of patients with aUC treated with recently approved agents. This initial analysis focused on patients treated with EV. Patient data were ed from chart reviews by investigators at each site. The observed response rate (ORR) was investigator‐assessed for patients with at least 1 post‐baseline scan or clear evidence of clinical progression. ORRs were compared across subsets of interest for patients treated with EV monotherapy.
Results
The initial UNITE analysis included 304 patients from 16 institutions; 260 of these patients were treated with EV monotherapy and included in the analyses. In the monotherapy cohort, the ORR was 52%, and it was >40% in all reported subsets of interest, including patients with comorbidities previously excluded from clinical trials (baseline renal impairment, diabetes, and neuropathy) and patients with fibroblast growth factor receptor 3 (FGFR3) alterations. Progression‐free survival and overall survival were 6.8 and 14.4 months, respectively. Patients with a pure urothelial histology had a higher ORR than patients with a variant histology component (58% vs 42%; P = .06).
Conclusions
In a large retrospective cohort, responses to EV monotherapy were consistent with data previously reported in clinical trials and were also observed in various patient subsets, including patients with variant histology, patients with FGFR3 alterations, and patients previously excluded from clinical trials with an estimated glomerular filtration rate < 30 mL/min and significant comorbidities.
Lay Summary
Enfortumab vedotin, approved by the Food and Drug Administration in 2019, is an important new drug for the treatment of patients with advanced bladder cancer.
This study looks at the effectiveness of enfortumab vedotin as it has been used at multiple centers since approval, and focuses on important patient populations previously excluded from clinical trials. These populations include patients with decreased kidney function, diabetes, and important mutations.
Enfortumab vedotin is effective for treating these patients. Previously reported clinical trial data have been replicated in this real‐world setting, and support the use of this drug in broader patient populations.
On the basis of initial data from the Urothelial Cancer Network to Investigate Therapeutic Experiences study, enfortumab vedotin has activity in diverse populations of patients with urothelial cancer, including patients with variant histologies, patients with FGFR3 alterations, and patients with significant comorbidities previously excluded from clinical trials. Additionally, in this large, multi‐institutional, retrospective cohort of patients with urothelial cancer, responses to enfortumab vedotin in patients treated outside a clinical trial are consistent with and complementary to prior clinical trial data.
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