SUMMARY

• Summarized below are real-world, observational and retrospective studies and registries which evaluated the step-up dosing (SUD) of TECVAYLI in adult patients with multiple myeloma (MM).^1-3
• Additional data in smaller sample sizes have been identified and are included below for your reference.

Real-world data

Tan et al (2023)¹ presented a retrospective, observational study that evaluated patient profiles and the SUD process as well as the real-world incidence and management of cytokine release syndrome (CRS) in patients with MM who had initiated TECVAYLI in a hospital setting in the first 5 months of United States (US) market availability.

Study Design/Methods

• The study used the Premier Healthcare Database (which represents 1 in 5 inpatient hospital stays in the US from >600 acute care hospitals), a hospital chargemaster database containing inpatient and outpatient visits from nonprofit, nongovernmental, community, and teaching hospitals and health systems.
• Eligible patients included adults (≥18 years of age) with MM who received ≥1 TECVAYLI administration between November 1, 2022, and April 1, 2023, and were not part of a clinical trial.
• Patients who met the following criteria were defined as having a complete SUD period:
  • Patients with dosage data available.
  • Patients who had received a TECVAYLI 30 mg/3 mL vial; the date of the hospital encounter for the first 30 mg/3 mL vial was considered the first dose of the SUD period and used as an index.
  • Patients who subsequently received a TECVAYLI 153 mg/1.7 mL vial between 1 and 7 days following a prior 30 mg/3 mL vial; the first 153 mg/1.7 mL vial was considered the last dose of the SUD period.
• Patients who did not meet the above criteria were considered as having an incomplete SUD period.

Results

• A total of 113 patients were included in the study.

Step-up Dosing

• Among the 88 patients with dosage information, 58 (65.9%) had a complete SUD period at data cutoff, with all doses administered in a single inpatient admission.
• In total, 31 (53.5%) patients started TECVAYLI on day 1 of admission.
• The mean (standard deviation [SD]) length of stay (LOS) was 8.6 (1.7) days after omitting extreme outliers.
• A 3-day (39.7%) or 2-day (20.7%) interval or other (39.7%) intervals were reported between SUDs.

CRS Incidence and Management

• CRS events among patients who completed TECVAYLI SUD are presented in Table: CRS Events Among Patients Who Completed TECVAYLI SUD.
• In total, 100% of patients received corticosteroids, 98.3% received diphenhydramine, 87.9% received acetaminophen, and 10.3% received tocilizumab at any time during SUD.

Banerjee et al (2023)² presented a retrospective, observational analysis that evaluated patient profiles and healthcare resource utilization (HCRU) during the SUD period and the incidence of real-world CRS in patients with MM who had received TECVAYLI.

Study Design/Methods

• The study utilized data from the All-payer Real-world Multiple Myeloma Research-ready Data (ARMMRD) registry, sourced from STATinMED real-world data (RWD) insights, encompassing all-payer claims data that spanned approximately 87% of the nationally insured population in the US, spanning from January 1, 2014, to July 31, 2023.
• Adult patients (≥18 years of age) with MM who had ≥1 commercial TECVAYLI claim within the ARMMRD registry during the identification period (October 26, 2022, to July 31, 2023) were included in this study.
• The index date was determined as the earliest outpatient claim for a TECVAYLI 30 mg/3 mL vial or the admission date of the earliest hospitalization claim containing TECVAYLI.
• Patients who had received TECVAYLI on or before the approval date were excluded from the analysis.
• A claim-based algorithm was employed to identify patients with a complete SUD period based on the following criteria:
  • Patients who have had ≥1 inpatient admission or ≥1 outpatient claim for a TECVAYLI 30 mg/3 mL vial; the earliest admission date (if inpatient) or claim date (if outpatient) was defined as the start date of the SUD period.
  • All inpatient or outpatient claims for TECVAYLI with a <5-day gap between claims within a 21-day continuous enrollment period were rolled up as part of the SUD period. If the index claim was an outpatient claim, an additional outpatient claim for a TECVAYLI 153 mg/1.7 mL vial was required.
  • The end date of the SUD period was the discharge date, if the last encounter was an inpatient admission, or claim date +4 days, if the last encounter was an outpatient claim for a 153 mg/1.7 mL vial.

Results

• In total, 182 patients with a claim for TECVAYLI were included in the study.
• The mean (SD) Quan-Charlson Comorbidity Index (Quan-CCI) score was 4.0 (3.6) for the overall population, and the cohort indexed in March 2023 had the highest Quan-CCI score of 5.6 (3.8).
• Of the 92 patients who met the criteria for evaluable treatment history, 15 (16.3%) had prior exposure to a commercial B-cell maturation antigen (BCMA) therapy.

HCRU During SUD

• Of the 131 patients who had a complete SUD period by the data cutoff, 112 (85.5%) completed TECVAYLI SUD in 1 inpatient admission.
  • Of the 19 (14.5%) patients with >1 encounter with SUD, 2 (10.5%) were all inpatient admissions, 5 (26.3%) were all outpatient administrations, and 12 (63.2%) were in hybrid inpatient/outpatient settings.
• The median (interquartile range) LOS was 8.0 (4.0) days (mean [SD], 8.5 [3.0] days) after omitting extreme outliers (N=115) among 126 (96.2%) patients with ≥1 TECVAYLI-related hospitalization during SUD.
• Over time, the mean (SD) LOS in patients who had ≥1 TECVAYLI-related hospitalization during SUD decreased from 11.4 (9.0) days for patients indexed through February 2023 to 7.0 (1.4) days for those indexed in July 2023 (outliers included). See Table: Mean LOS Among Patients With ≥1 TECVAYLI-Related Admission During SUD (n=126).

Safety - CRS Events

• Of the 131 patients with a complete SUD period, 54 (41.2%) had an International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) diagnosis code for CRS and 32 (24.4%) experienced CRS-related symptoms per the Keating algorithm. See Table: Real-World CRS Events Among Patients Who Completed TECVAYLI SUD.

• During the complete SUD period, 7 (5.3%) patients had tocilizumab-related claims, 14 (10.7%) had dexamethasone-related claims, 8 (6.1%) had antihistamine-related claims, and 4 (3.1%) had acetaminophen-related claims.

Banerjee et al (2023)³ presented a real-world, retrospective analysis of Acentrus MM electronic medical records (EMRs) that evaluated the dosing patterns, HCRU, and the early safety outcomes during TECVAYLI SUD among US patients receiving TECVAYLI.

Study Design/Methods

• Adult patients (≥18 years old) with MM who had received ≥1 dose of TECVAYLI between October 26, 2022, and May 31, 2023, were included.
• Patients with diagnosis codes for clinical trials on the index date or those who had indicators of receiving TECVAYLI in a clinical trial setting were excluded.
• Patients were indexed on the day of the first TECVAYLI dose.
• Patient characteristics were captured during the 6-month baseline period before the index date.
• Dosing patterns, healthcare settings (inpatient or outpatient), LOS at the hospital, and rate, severity, and treatment for CRS and immune effector cell-associated neurotoxicity syndrome (ICANS) were described among patients with complete SUD data.
• Patients were considered to have complete SUD data if they had received the 2 SUDs (30 mg/3 mL vial size) and the first treatment dose (153 mg/1.7 mL vial size), with strength confirmed in the database, and had at least 7 days of data or the next dose observed after the first treatment dose (to allow sufficient time for capturing treatment outcomes of the first dose) by the data cutoff.

Results

• A total of 104 patients (median age, 65 years [range, 43-89]; male, 58%) were included in the study.
• Prevalent baseline comorbidities included anemia (67%), hypertension (57%), renal impairment/failure (54%), lytic bone lesions (35%), hypogammaglobulinemia (25%), and extramedullary plasmacytomas (12%).
• Twenty five percent of patients were previously treated with BCMA-targeted therapies.

SUD Patterns

• In the cohort of 104 patients, data pertaining to SUD were available for 76 patients. Within this subset, 65 patients (86%) completed the SUD in an all-inpatient setting. Additionally, 64/65 (98%) patients received all 3 doses in a single admission. Alternatively, 10 patients (13%) received all 3 doses in an outpatient setting. One patient received SUD in inpatient as well as outpatient settings.
• A total of 42% of patients had an exact 2-day dosing interval (eg, days 1-3-5), and 16% of patients had an exact 3-day dosing interval (eg, days 1-4-7); 75% of patients received the third dose within 7 days of TECVAYLI initiation.
• Among the 36 patients with detailed inpatient data, the median LOS for inpatient SUD was 8.0 days, excluding 1 extreme outlier. Median LOS generally trended downward over time, from 11 days in December 2022 to 6.5 days in May 2023. See Table: Hospital LOS for TECVAYLI SUD by Index Month.

Safety

• Data pertaining to CRS and ICANS in patients with complete SUD (n=76) have been summarized in Table: CRS and ICANS Outcomes in Patients With Complete SUD.
• A total of 99% of patients received acetaminophen, 96% received diphenhydramine, and 71% received corticosteroids on the days of TECVAYLI administration.
  • No patients received prophylactic treatments within 2 days prior to the administration of the first TECVAYLI dose.
• A total of 3% of patients received tocilizumab on the same day as their first dose (unclear whether tocilizumab was given for prophylaxis or treatment), and 12% received tocilizumab after TECVAYLI dosing.

Additional data

• Graf et al (2024)⁴ published a retrospective, single center analysis evaluating the safety and utility of a condensed SUD schedule for TECVAYLI in 25 patients at the Medical University of South Carolina.
• Kawasaki et al (2024)⁵ published a retrospective, single center exploratory analysis evaluating safety outcomes of a TECVAYLI accelerated 2-day SUD escalation in 27 patients at the University of California (UC) Davis Health system.

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File databases (and/or other resources, including internal/external databases) was conducted on 10 December 2024.