Restarting TECVAYLI After Dosage Delay

PRODUCT LABELING

Restarting TECVAYLI After Dosage Delay

• If a dose of TECVAYLI is delayed, restart therapy based on: Recommendations for Restarting Therapy With TECVAYLI After Dose Delay and resume the treatment schedule accordingly.¹
• Administer pretreatment medications as indicated in Recommendations for Restarting Therapy With TECVAYLI After Dose Delay.¹
• Due to the risk of cytokine release syndrome (CRS) and neurologic toxicity, including immune effector cell-associated neurotoxicity (ICANS), patients should be hospitalized for 48 hours after administration of both step-up dose (SUD) 1 and SUD 2. Instruct patients to remain within proximity of a healthcare facility and monitor them daily for
  48 hours after the first treatment dose within the TECVAYLI step-up dosing schedule.¹

CLINICAL DATA

Quijano Cardé et al (2026)² published the results of population pharmacokinetic (PK) and cytokine dynamics modeling along with retrospective clinical analysis of the CRS data from MajesTEC-1 to evaluate extended dosing intervals of TECVAYLI for updated restarting recommendations.

Study Design/Methods

• Population PK analysis was conducted using a two‑compartment model with first-order absorption and parallel time‑independent and time-dependent elimination pathways.²
  • A virtual population of 1000 patients (generated from individual baseline demographics and disease-related characteristics) representative of the MajesTEC-1 population along with the population PK model projected steady-state concentration-time profiles occurring after 2 simulated dose delays after the thirteenth 1.5 mg/kg weekly (QW) dose and the seventh 1.5 mg/kg biweekly (Q2W) dose.
  • Subsequently, these serum concentrations were compared with the estimated median trough concentrations (C_trough) associated with SUDs, which provided time windows for retrospective analysis of the clinical data related to CRS.
  • Following prolonged dose interruptions, a sensitivity analysis of the population PK model predictions was conducted, considering that the potential re-expression of B-cell maturation antigen (BCMA) and immune recovery after treatment interruption would restore target‑mediated drug disposition and increase TECVAYLI clearance.
  • In patients receiving the recommended phase 2 dose (RP2D) who experienced prolonged dosing intervals (>28 days; n=21), post hoc model-based simulations of individual PK profiles were generated and compared with the observed PK data.
• Based on TECVAYLI’s mechanism of action and calibrated using clinical data, a quantitative systems pharmacology (QSP) model was applied to simulate cytokine dynamics and support switching of TECVAYLI dosing from QW to Q2W in patients who reached a sustained complete response (CR).²
  • The QSP model was updated using data including longitudinal serum concentrations of interleukin (IL)-6 and IL-10, incidence and severity of CRS, and dosing information for TECVAYLI and tocilizumab.
• A retrospective clinical safety analysis was performed using MajesTEC‑1 data with a data cutoff of August 22, 2023. Population PK analysis predictions were used to define the time windows for evaluation of repeat SUD and incidence of CRS events during prolonged dosing intervals (>28-62 days, ≥63-111 days, and ≥112 days) per American Society for Transplantation and Cellular Therapy (ASTCT) criteria.²

Results

Population PK Modeling

• The population PK modeling analysis demonstrated satisfactory concordance between observed serum concentrations and modelestimated values after prolonged dosing intervals.²
• At steady state, the median serum TECVAYLI concentrations at 62 days after the last QW dose (1.05 μg/mL) or Q2W dose (0.839 μg/mL) were similar to or slightly lower than the median serum C_trough estimated after SUD 2 (1.05 μg/mL).²
• Median serum TECVAYLI concentrations at 111 days after the last QW dose (0.246 μg/mL) or Q2W dose (0.195 μg/mL) at steady state were estimated to be similar to or higher than the median serum C_trough estimated after SUD 1 (0.168 μg/mL).²

QSP Model Simulations of Cytokine Levels Following Prolonged Dosing Intervals

• Median maximal concentrations of IL‑6 and IL‑10 observed after restarting TECVAYLI QW dosing following 62- or 111-day treatment delays were comparable to or lower than the median concentrations observed after initial TECVAYLI SUDs.²
  • In simulated patients who maintained ≥ partial response (PR) until onset of dosing delay, median maximal cytokine levels after treatment reinitiation were ~30%-45% lower than median levels observed following initial SUDs during QW dosing.
• Median maximal concentrations of IL‑6 and IL‑10 observed after restarting TECVAYLI Q2W dosing following 62- or 111-day treatment delays were lower than median concentrations observed after initial TECVAYLI SUDs.²
  • In simulated patients who maintained ≥PR until onset of dosing delay, median maximal cytokine levels after treatment reinitiation were ~42%-50% lower than median levels observed following initial SUDs during Q2W dosing.
• A reduction in median maximal cytokine levels was observed when treatment was resumed treatment at 1.5 mg/kg QW after a 62-day dose delay, as well as when treatment was restarted at SUD 2 following a 111-day dose delay. This was consistent with findings of dose-delay simulations following QW TECVAYLI dosing.²
• The medial estimated ratios of peak IL-6 and IL-10 levels are summarized in Table: Model Estimated Ratios of Maximal IL-6 And IL-10 Concentrations Following Proposed Restart Recommendations After Dose Delay From QW Or Q2W Dosing at SS to Their Respective Maximal Values After Initial SUDs.

Retrospective Clinical Analysis of Prolonged Dosing Intervals

• Of 165 patients in the MajesTEC1 RP2D population, 61 patients experienced prolonged dosing intervals (>28 days) during QW or less frequent dosing. A total of 128 prolonged dosing intervals were reported during TECVAYLI treatment.²
• Most prolonged intervals were >28-62 days. See Table: CRS Occurrence After Prolonged Dosing Intervals in Retrospective Clinical Analysis for additional details.²
• Only 2 patients (with 1 dose delay each) had 3 low-grade CRS events after prolonged dosing intervals of >28-62 days.²
• All other >28-62day intervals were not associated with CRS events upon treatment restart; for 78% of these intervals, patients resumed treatment at 1.5 mg/kg without repeat SUD.²
• Fifteen patients had 18 dosing intervals of ≥63-111 days (50% restarted at SUD2), and 7 patients had 8 intervals of ≥112 days (50% restarted at SUD1 followed by SUD2).²
• No CRS events were observed at treatment reinitiation for dosing intervals of ≥63 days.²

Additional data

Other relevant data have been identified in addition to the data summarized above:

• van de Donk et al (2024)³ applied population pharmacokinetic modeling to a retrospective clinical analysis of MajesTEC-1 (at a data cutoff of August 22, 2023) to evaluate repeat SUD and CRS events in the setting of prolonged dosing intervals (>28-62 days, ≥63-111 days, and ≥112 days).
• Tan et al (2025)⁴ examined the impact of omitting repeat SUD on the incidence of CRS and/or ICANS in TECVAYLI or talquetamab patients restarting therapy after a prolonged dose delay (>28 days) outside of a clinical trial at Memorial Sloan Kettering.

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 04 May 2026.