Treatment Pattern, Healthcare Resource Utilization and Symptom Burden Among Patients with Triple Class Exposed Multiple Myeloma: A Population-Based Cohort Study.

PURPOSE: This study aims to describe the treatment patterns, outcomes, health care utilization and symptom burden of triple class exposed (TCE) relapsed/refractory patents with multiple myeloma (MM) receiving a subsequent line of treatment (LOT). METHODS: This is a retrospective observational cohort study using administrative databases in Ontario, Canada. Outcomes were captured for TCE patients receiving a subsequent LOT and included: treatment regimen details, time to next treatment (TTNT), overall survival (OS), health care utilization, palliative care referral, and patient reported symptoms. RESULTS: Of the 16,777 patients diagnosed with MM between 2007-2021 in Ontario, 1358 (8%) patients were classified as TCE. Among the TCE MM patients, 489 (36%) received a subsequent LOT. The two most commonly administered therapies post TCE were carfilzomib/dexamethasone (n = 111, 22%) and pomalidomide/dexamethasone(n = 95, 19%). Median TTNT was 1.7 months (95%CI 1.2-2.4 months) and median OS 12.8 months (95%CI 10.8-16.5). Healthcare utilization was high with 276 (56%) of patients evaluated in an emergency department (ED) or admitted to hospital. There was high symptom burden as reported by patients with moderate-severe impairment in well-being, fatigue, pain and drowsiness noted in greater than 25% of the cohort. Palliative care referrals rates were low with only 10% (n = 48) patients referred to palliative care. Among the patients that died during study follow up, the majority died in hospital (n = 147,44%). CONCLUSION: Our study reports one of the largest series of real-world TCE patients published and demonstrates the poor outcomes of TCE patients receiving a subsequent LOT.

Antibodies and bispecifics for multiple myeloma: effective effector therapy.

The therapeutic landscape in multiple myeloma (MM) has changed dramatically over the last 2 decades. With the introduction of novel immunotherapies, patients with MM can expect deeper responses, longer remissions, and improved overall survival. Since its approval by the US Food and Drug Administration in 2015, the monoclonal antibody specific for CD38, daratumumab, has been incorporated into both frontline and relapsed treatment regimens. Its role as a maintenance therapy is currently being explored. Subsequently, a variety of novel antibody therapeutics have evolved from the success of daratumumab, using similar concepts to target the malignant plasma cell clone. Noteworthy naked monoclonal antibodies include isatuximab, another agent directed against CD38, and elotuzumab, an agent directed against SLAM family member 7. Antibody-drug conjugates, complex molecules composed of an antibody tethered to a cytotoxic drug, target malignant cells and deliver a lethal payload. The first to market is belantamab mafodotin, which targets B-cell maturation antigen (BCMA) on malignant plasma cells and delivers a potent microtubule inhibitor, monomethyl auristatin F. Additionally, bispecific T-cell antibodies are in development that engage the immune system directly by simultaneously binding CD3 on T cells and a target epitope-such as BCMA, G-protein coupled receptor family C group 5 member D (GPRC5d), and Fc receptor homologue 5 (FcRH5)-on malignant cells. Currently, teclistamab, an anti-BCMA bispecific, is closest to approval for commercial use. In this review, we explore the evolving landscape of antibodies in the treatment of MM, including their role in frontline and relapse settings.

Optimal Timing of Allogeneic Stem Cell Transplantation for Primary Myelofibrosis.

Primary myelofibrosis (PMF) is a chronic myeloproliferative neoplasm characterized by cytopenias, splenomegaly, and risk of leukemic transformation. In light of newer therapies, such as ruxolitinib, that are not curative but improve quality of life, the timing of transplantation needs more in-depth analysis to determine which patients would benefit from an early versus a delayed transplantation strategy. Because prospective clinical trials are impractical for diseases with only one curative option, such as PMF, we developed a Markov cohort model to simulate the long-term disease trajectory in patients with PMF and predict the optimal timing of transplantation stratified by Dynamic International Prognostic Scoring System (DIPSS) risk. In this decision model, a hypothetical cohort of patients begins in the alive with PMF state and can transition monthly to other health states. Transition probabilities were acquired from published literature. We performed probabilistic analyses by jointly varying all model parameters over 1000 simulations. Irrespective of DIPSS risk, all patients with PMF benefited from transplantation with respect to life expectancy gained. Life expectancy gains from transplantation peaked at 9.7 months (95% confidence interval [CI], 9.5 to 9.9 months) from diagnosis in patients with high-risk disease and at 16.6 months (95% CI, 16.4 to 16.8 months) from diagnosis in patients with intermediate-2 disease. Patients with intermediate-1 risk had a delayed peak in net gain in life expectancy at 20.5 months (95% CI, 20.2 to 20.7 months). Patients with low-risk disease had a greater net gain in life expectancy the longer that transplantation was delayed; this trend plateaued at 29 to 45 months. Our modeling suggests that preparation for transplantation is indicated upfront for patients diagnosed with intermediate-2 risk and high-risk PMF, whereas this can be delayed for low-risk or intermediate-1 risk disease.