Evolving Real-World Characteristics and Step-up Dosing Among Early Initiators of Teclistamab for Multiple Myeloma - a National All-Payer Claims Database Study

Abstract

Introduction: Teclistamab, a first-in-class B-cell maturation antigen (BCMA) x CD3 bispecific antibody with a personalized, weight-based dosing schedule, gained United States (US) regulatory approval in October 2022 for the treatment of triple-class exposed relapsed/refractory multiple myeloma (MM). Prior real-world analyses using hospital chargemaster or single-center data (Tan SOHO 2023, Firestone ASCO 2023) found that early initiators of teclistamab were elderly, diverse, frail, heavily pretreated, and had significant comorbidities. The evolving characteristics of patients receiving teclistamab over time and the operationalization of step-up dosing (SUD) nationally have not been characterized. Methods: This is a retrospective, observational, descriptive study using the All-payer Real-world Multiple Myeloma Research-ready Data (ARMMRD) registry, derived from STATinMED RWD Insights all-payer claims data that covers approximately 87% of the nationally insured population in the US, from January 1, 2014 to May 31, 2023. The intake period was October 26, 2022 to May 31, 2023; patients were indexed on the earliest outpatient claim of a teclistamab 30mg/3mL vial or admission date of the earliest hospitalization with teclistamab. A claims-based algorithm was applied to best approximate the SUD period per label which includes the first two step-up doses and the first treatment dose. Patients were included if they had ≥1 MM diagnosis claim on or any time prior to index, age ≥18 years on index, and continuous eligibility for 6 months before index (baseline period). Patients who received teclistamab on or before the approval date were excluded. Patient characteristics and length of SUD were analyzed descriptively across 4 index timing-based cohorts: 1) those indexed through February 2023; 2) in March 2023; 3) in April 2023; and 4) in May 2023. Results: A total of 124 patients were included in the study. Median (interquartile range [IQR]) age was 71.5 (14.5) years; 33.9% were age ≥75 years; 72.6% had Medicare insurance; 49.2% were male. Most were White (62.1%) and non-Hispanic (63.7%), with 12.1% Black. The mean (standard deviation [SD]) Quan-Charlson Comorbidity Index score was 4.2 (3.6) for the overall population; the cohort indexed in March 2023 had the highest score at 5.8 (3.9). Similarly, while the overall comorbidity burden was high in the overall population, the cohort indexed in March 2023 had the highest rates for many comorbidities (Table 1). Among 68 patients with continuous eligibility since the initial MM diagnosis, 16.2% had prior exposure to a commercial BCMA therapy: 10.3% were exposed to BCMA chimeric antigen receptor (CAR)-T therapy and 8.8% to belantamab mafodotin. Among 99 patients who completed SUD by the data cutoff, 87 (87.9%) completed SUD in one inpatient admission, 4 (4.0%) fully outpatient, and 8 (8.1%) in hybrid inpatient/outpatient settings. Among patients with ≥1 teclistamab hospitalization, the median (IQR) length of stay was 8.0 (4.0) days, with mean (SD) of 8.3 (2.9) days after omitting extreme outliers. Over time, the mean (SD) length of the SUD period shortened from 12.1 (9.0) days to 6.7 (1.2) days. However, the percentage of patients who received teclistamab SUD in one hospitalization remained relatively constant (Figure 1). Conclusion: This is the first national real-world study using all-payer claims data of patients initiating teclistamab in the first 7 months of market availability. Like prior reports, early initiators of this first-in-class bispecific represented a diverse and elderly population with substantial comorbidities; yet, across the index time-based cohorts, the average comorbidity index score fell. Teclistamab SUD was generally administered through a single hospitalization, which may reflect logistical considerations with adverse event monitoring and elective hospital readmissions. Nonetheless, the duration of SUD period appeared to shorten over time, and most admitted patients were discharged without delay. Study limitations include the nature of insurance claims data, small sample size per subgroup, and lack of granular data on CRS incidence and management; however, to our knowledge, this is the largest analysis of real-world teclistamab use to date. Additional analyses are warranted to understand evolving trends in teclistamab SUD and establish best practices as the field grows more familiar with bispecific antibodies in MM.