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BACKGROUND Survival is poor among patients with triple-class-exposed relapsed and refractory multiple myeloma. Idecabtagene vicleucel (ide-cel), a B-cell maturation antigen-directed chimeric antigen receptor (CAR) T-cell therapy, previously led to deep, durable responses in patients with heavily pretreated relapsed and refractory multiple myeloma. METHODS In this international, open-label, phase 3 trial involving adults with relapsed and refractory multiple myeloma who had received two to four regimens previously (including immunomodulatory agents, proteasome inhibitors, and daratumumab) and who had disease refractory to the last regimen, we randomly assigned patients in a 2:1 ratio to receive either ide-cel (dose range, 150x106 to 450x106 CAR-positive T cells) or one of five standard regimens. The primary end point was progression-free survival. Key secondary end points were overall response (partial response or better) and overall survival. Safety was assessed. RESULTS A total of 386 patients underwent randomization: 254 to ide-cel and 132 to a standard regimen. A total of 66% of the patients had triple-class-refractory disease, and 95% had daratumumab-refractory disease. At a median follow-up of 18.6 months, the median progression-free survival was 13.3 months in the ide-cel group, as compared with 4.4 months in the standard-regimen group (hazard ratio for disease progression or death, 0.49; 95% confidence interval, 0.38 to 0.65; P<0.001). A response occurred in 71% of the patients in the ide-cel group and in 42% of those in the standard-regimen group (P<0.001); a complete response occurred in 39% and 5%, respectively. Data on overall survival were immature. Adverse events of grade 3 or 4 occurred in 93% of the patients in the ide-cel group and in 75% of those in the standard-regimen group. Among the 225 patients who received ide-cel, cytokine release syndrome occurred in 88%, with 5% having an event of grade 3 or higher, and investigator-identified neurotoxic effects occurred in 15%, with 3% having an event of grade 3 or higher. CONCLUSIONS Ide-cel therapy significantly prolonged progression-free survival and improved response as compared with standard regimens in patients with triple-class-exposed relapsed and refractory multiple myeloma who had received two to four regimens previously. The toxicity of ide-cel was consistent with previous reports. (Funded by 2seventy bio and Celgene, a Bristol-Myers Squibb company; KarMMa-3 ClinicalTrials.gov number, NCT03651128.). [ABSTRACT FROM AUTHOR]

RT is an important therapeutic modality utilized at various stages along the treatment continuum in MM. However, there has been no national study of RT utilization and data on the factors that influence use are lacking due to its palliative nature and the fact that RT can be used multiple times over the course of MM treatment. The Connect® MM Registry is a largely community-based registry that provides a unique opportunity to evaluate real-world use and factors that influence RT use in MM treatment. The Connect MM Registry is a large, US, multicenter, prospective observational cohort study of patients (pts) aged ≥ 18 y with newly diagnosed MM from 250 community, academic, and government sites. This analysis investigated Registry pts who received RT. RT utilization was captured quarterly over the entire course of pt treatment, in the first 6 months from study enrollment and in the last 6 months prior to death. Data from 9/28/2009 — 2/4/2021 were used in this analysis. The Connect MM Registry included 3011 pts of whom 903 (30%) received RT at any time. Twenty-one percent (636/3011) received RT within the first 6 months of study enrollment and 16% (241/1526) within the last 6 months before death (among all death pts). Overall, pts were predominantly white (83%), male (57%), with a median age of 67 y (range 24 – 94) and received a triplet anti-MM regimen (55%). At baseline, most common indications for RT were pain (65%), impending fracture (13%), or neurologic compression (12%). On multivariable analysis, overall RT use was significantly less common in pts with Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 – 1 vs 2+ (odds ratio [OR], 0.58; P = 0.0014) and more common in ISS stage I + II vs III pts (OR, 1.61; P = 0.0009). We observed no statistically significant difference regarding pt age, sex, race/ethnicity, insurance status, geographic region, intent to transplant, or use of novel anti-MM agents in first line of treatment. In the first 6 months after study enrollment, there was more than double the odds of RT use in pts with ISS I+II vs III (OR, 2.07; P < 0.001) and in pts with ECOG PS 0–1 vs 2+ (OR, 0.46; P < 0.001). No other sociodemographic or clinical factors studied were significant. In the 6 months before death, the only factor associated with increased RT use was increasing lines of MM therapy (OR, 1.19; P < 0.001). These results from the CONNECT MM Registry, representative of real-world practice, show that even in the era of novel anti-MM agents, RT is used frequently for pt care. RT use is dictated by clinical factors, including PS and disease stage, rather than sociodemographic factors. Earlier in MM diagnosis, RT may be used as an adjunct to palliate symptoms (poor PS) or to delay systemic therapy (early stage). Toward the end of life, RT is more frequently used for palliation, with limited systemic options after multiple lines of therapy. [ABSTRACT FROM AUTHOR]