Person:

Cliff, Edward

Smoldering multiple myeloma (SMM) is an asymptomatic condition that precedes newly diagnosed multiple myeloma (ND MM) and is present in ~1 of 200 individuals (0.5%) aged >40 years.1 The optimal management of patients with high-risk SMM (HR-SMM) remains controversial. Among proponents of early intervention in HR-SMM, there are predominantly 2 strategies that have been tested in clinical trials: 1 with low-intensity regimens, such as lenalidomide and dexamethasone,2,3 aimed at preventing morbidites such as fractures and renal failure, and another strategy which instead uses intensive regimens with the aim of cure. Intensive approaches include multidrug combination induction therapy with or without high-dose melphalan and autologous hematopoietic cell transplantation (HDM-AHCT).4-6 An important distinction between these 2 strategies is that although the former has been subjected to randomized controlled trials (RCTs) against observation, the latter, to date, has only been tested in single-arm studies.

Bispecific antibodies, a novel immunotherapy with promising efficacy against multiple myeloma, form immune synapses between T-cell surface marker CD3 and malignant cell markers, including B-cell maturation antigen (BCMA), FcRH5, and G protein–coupled receptor GPRC5D. These bispecific antibodies so effectively deplete plasma cells (and to some extent T-cells) that patients are at increased risk of developing infections. A systematic review and meta-analysis of infections in published studies of patients with myeloma treated with bispecific antibodies was conducted to better characterize the infection risks. A literature search used MEDLINE, EMBASE, and Cochrane to identify relevant studies between inception and February 10, 2023, including major conference presentations. Phase 1b-3 clinical trials and observational studies were included. Sixteen clinical trials comprising 1666 patients were included. Median follow-up was 7.6 months and 38% of the cohort had penta-drug refractory disease. Pooled prevalence of all-grade infections was 56%, whereas the prevalence of grade ≥3 infections was 24%. Patients who were treated with BCMA-targeted bispecifics had significantly higher rates of grade ≥3 infections than non-BCMA bispecifics (25% vs 20%). Similarly, patients treated with bispecifics in combination with other agents had significantly higher rate of all-grade infection than those receiving monotherapy (71% vs 52%). In observational studies (n = 293), excluded from the primary analysis to ensure no overlap with patients in clinical trials, several infections classically associated with T-cell depletion were identified. This systematic review identifies BCMA-targeted bispecifics and bispecific combination therapy as having higher infection risk, requiring vigilant infection screening and prophylaxis strategies.

This cross-sectional study analyzes trends in Medicare Part D use and spending on oral-targeted drugs for chronic lymphocytic leukemia from 2014 to 2020.