Hanna, Kirollos S.

Introduction: Chronic lymphocytic leukaemia (CLL) is the most common leukaemia type. In 2020, there were an estimated 207,463 people living with CLL, with an annual incidence of approximately 4.9 per 100,000 in the United States (US). Zanubrutinib is a Bruton tyrosine kinase inhibitor that is FDA-approved and an NCCN preferred and recommended treatment of CLL. In the phase 3 ALPINE trial (NCT03734016), zanubrutinib elicited a significantly higher overall response rate and significantly longer progression-free survival (PFS) than ibrutinib. This study aimed to compare zanubrutinib versus ibrutinib in Relapsed/Refractory (R/R) CLL by calculating the number needed to treat (NNT) to avoid one progression or death and associated incremental costs. Methods:A health-economic model was developed to evaluate the number of R/R CLL patients needed to be treated to avoid a progression or death from the US payer perspective. Payer blend was assumed with 40% Commercial and 60% Medicare payer mix. Clinical efficacy data were extracted from the ALPINE trial. Final analysis result of 24-month PFS (79.5% for zanubrutinib and 67.3% for ibrutinib) was used for the base-case analysis in the model. Treatment, adverse event management, other medical resource use, and subsequent treatment costs were considered in the model. The NNT, incremental cost per treated patient, and incremental cost per additional patient with progression or death were captured. Deterministic sensitivity analyses were conducted to assess parameter uncertainties and explore key model drivers. Scenario analyses were conducted to test the impact of different PFS estimates. Results: The base-case results fromthe NNT model showed that for every 8 patients treated with zanubrutinib, 1 event of progression or death would be avoided compared to using ibrutinib. The total costs per patient treated with zanubrutinib and ibrutinib are $370,558 and $430,150, respectively, with a cost savings of $59,593 associated with using zanubrutinib (Table). Drug costs and PFS have the greatest impact on the incremental cost per patient. Varying the PFS scenarios, including adjustment with drug interruption, COVID death, or treatment discontinuation, change the NNT from 8 to 12, and are associated with cost savings of $58,179 to $67,153 per zanubrutinib-treated patient in a 24-month time frame. Applying the model result to a hypothetical scenario of a clinical practice of 100 patients treated with zanubrutinib versus ibrutinib suggest that approximately 13 patients will avoid disease progression events or death. Conclusions: The NNT model suggests thatusing zanubrutinib to treat R/R CLL patients, compared to ibrutinib, will result in more favorable clinical and economic outcomes in the US.

52 Background: When combination medical therapy incorporates both IV and oral anti-cancer agents, patients may experience compound side effects and face challenges with treatment adherence. To assess how community cancer programs may improve care coordination for patients receiving combination IV/oral systemic therapy, the Association of Community Cancer Centers (ACCC) conducted a mixed-methods study that involved healthcare professionals (HCPs), patients and caregivers. Methods: The study followed a sequential quantitative-qualitative design to answer questions around the barriers or challenges associated with combination IV/oral systemic therapy. The quantitative phase included an online survey of HCPs (by ACCC) and a survey of patients and caregivers (by Edge Research, in collaboration with several patient advocacy organizations). In the quantitative phase, the survey results were contextualized through two HCP focus groups and individual HCP interviews. Results: Comparing and contrasting the patient survey (n = 113) and HCP survey (n = 157) results revealed insights around the following themes: Top Challenges: Patients felt their top challenges were side effects (57.5%); inconvenience going to medical appointments (37.2%); and financial burden (36.3%). HCPs perceived top challenges as cost of care to the patient (24.0%); coordination and delivery of oral agents (22.1%); and health insurance coverage (21.9%). In focus groups, HCPs explained how they were investing significant staffing resources to prevent and mitigate financial toxicity, especially for patients receiving oral therapies. Methods of Communication: 35.4% of patients “highly preferred” using email to communicate with HCPs about their combination regimens. However, HCPs felt that email was one of the least effective methods of communicating with patients. In focus groups, HCPs agreed that email is convenient when communicating about non-urgent matters. However, they were concerned that some patients may use email to communicate about urgent issues. Treatment-related AEs: When patients experienced treatment-related AEs, 30.1% said their clinicians tried a dose modification or hold. HCPs had mixed perceptions regarding the effectiveness of dose holidays. Those who felt this was highly effective included: advanced practice providers (42.9%), nurses (28.1%); oncologists (16.7%); and pharmacists (16.7%). Conclusions: This study identifies opportunities to improve care coordination for patients receiving combination IV/oral systemic anti-cancer regimens. These findings may inform the creation and dissemination of effective practices and quality improvement projects. These results may also help cancer programs tailor resources and incorporate proactive steps to address some of the key challenges patients may face.

Objective Chronic lymphocytic leukemia and small lymphocytic lymphoma remain the most prevalent adult leukemia in Western countries. Novel therapeutics have established long-term efficacy and have changed the landscape in patient management. In contrast, novel approaches pose opportunities for patients to be treated for finite durations. In this manuscript, we highlight long-term safety and efficacy data with Bruton's tyrosine kinase inhibitors and combination BCL2 + anti-CD20 therapies. We also offer key considerations for treatment selection and outline ongoing trials which may continue to expand therapeutic options and approaches. Data sources An electronic search of the PubMed database was performed to obtain key literature in chronic lymphocytic leukemia and small lymphocytic lymphoma published using the following search terms: chronic lymphocytic leukemia/small lymphocytic lymphoma, Richter syndrome, and histologic transformation. The search results were narrowed by selecting studies in humans published in English. Results were confined to the following article types: Clinical Trial, Phase II; Clinical Trial, Phase III; Clinical Trial, Phase IV; Guideline; Randomized Controlled Trial; Meta-Analysis; Systematic Reviews; and Validation Studies. Data summary Chronic lymphocytic leukemia and small lymphocytic lymphoma are different manifestations of the same disease and are managed in much the same way. Bruton's tyrosine kinase inhibitors have demonstrated long and durable efficacy benefits in patients with newly diagnosed chronic lymphocytic leukemia/small lymphocytic lymphoma and in the relapsed/refractory setting. Despite these benefits, long terms adverse events have posed challenges for patients and have led to treatment discontinuations. Additionally, the use of monotherapy Bruton's tyrosine kinase inhibitor's requires chronic use of the medications leading to added financial implications. BCL2 inhibition with venetoclax in combination with anti-CD20 monoclonal antibodies has offered a novel and finite treatment approach in frontline and relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma. Ongoing clinical trials are in investigating this modality further to enhance durable responses utilizing a combination Bruton's tyrosine kinase inhibitor's and BCL2 inhibitors. Conclusion The treatment armamentarium of chronic lymphocytic leukemia/small lymphocytic lymphoma continues to evolve. Despite the long term, durable responses with Bruton's tyrosine kinase inhibitor's, it is likely that finite treatment durations could become the standard of care as a result of continued, long-term responses.

Abstract Purpose The treatment landscape of advanced bladder cancer continues to evolve with novel therapeutics approved in recent years and many in the pipeline. Here we review the role of the novel agents enfortumab vedotin and sacituzumab govitecan in treatment of advanced disease. Summary Patients with advanced bladder cancer often first receive platinum-based therapy, while immune checkpoint inhibitors offer a maintenance option following cytotoxic chemotherapy or a second-line option. Despite various first- and second-line options, patients with significant comorbidities and treatment-related adverse events will experience disease progression requiring alternative treatment. Enfortumab vedotin and sacituzumab govitecan are novel antibody-drug conjugates approved in patients with advanced bladder cancer following platinum-based and immune checkpoint inhibitor therapy. Following platinum-based therapy and immunotherapy in patients with advanced bladder cancer, enfortumab vedotin, targeting Nectin-4, improves overall survival while sacituzumab govitecan, targeting Trop-2, is associated with a 27% response rate. With these new approaches to disease management, however, it remains critical to understand safety, efficacy, and operational considerations to optimize outcomes. Conclusion When selecting an antibody-drug conjugate to treat patients with bladder cancer, it is important to note the adverse event profile of each agent to optimize outcomes and safety for patients.

Multiple myeloma, a malignant neoplasm of plasma cells that accumulate in bone marrow, accounts for approximately 18% of hematologic malignancies in the United States. Patients are often treated with triplet therapy and may undergo stem cell transplantation. Despite effective therapies, multiple myeloma remains incurable. Patients often require maintenance therapy, and many will progress or relapsed following upfront treatment. Selection of treatment in the relapse/refractory setting is complex due numerous active therapeutic agents and combinations. Treatment is often tailored to prior exposure and duration. In 2020, three novel pharmacological agents were approved in the relapsed setting. We highlight the clinical safety and efficacy of selinexor, isatuximab-irfc, and belantamab mafodotin for patients with multiple myeloma.

Urothelial carcinoma is the sixth most common cancer type in the United States. Although most patients present with early stage disease which is associated with improved outcomes, many will progress to locally advanced or metastatic disease. Immune checkpoint inhibitors have significantly impacted the treatment paradigm for patients and have resulted in improved survival rates. Despite their proven efficacy, many ongoing clinical trials continue to refine combinations with chemotherapy, sequencing of therapies and the role of ligand expression. Additionally, novel targets have been identified for advanced urothelial carcinoma and have led to the approval of the antibody-drug conjugate, enfortumab vedotin, and the fibroblast growth factor receptor-targeted, erdafitinib. Enrollment in a clinical trial is strongly encouraged for all stages of advanced or metastatic disease. Numerous ongoing clinical trials are likely to impact the treatment armamentarium for patients. In this manuscript, we highlight key updates in the clinical management for patients and outline ongoing trials.

The national pandemic resulting from the novel coronavirus, COVID-19, has made the delivery of care for patients with cancer a challenge. There are competing risks of mortality from cancer versus serious complications and higher risk of death from COVID-19 in immunocompromised hosts. Furthermore, compounding these concerns is the inadequate supply of personal protective equipment, decreased hospital capacity, and paucity of effective treatments or vaccines to date for COVID-19. Guidance measures and recommendations have been published by national organizations aiming to facilitate the delivery of care in a safe and effective manner, many of which, are permanently adoptable interventions. Given the critical importance to continue chemotherapy, there remains additional interventions to further enhance patient safety while conserving healthcare resources such as adjustments in medication administration, reduction in laboratory or drug monitoring, and home delivery of specialty infusions. In this manuscript, we outline how to implement these actionable interventions of chemotherapy and supportive care delivery to further enhance the current precautionary measures while maintaining safe and effective patient care. Coupled with current published standards, these strategies can help alleviate the numerous challenges associated with this pandemic.