SUMMARY

• Janssen does not recommend the use of TECVAYLI in a manner that is inconsistent with the approved labeling.
• IMMUNO-PRISM (PRecision Intervention Smoldering Myeloma) is a multi-arm, randomized, phase 2 platform study investigating the efficacy of TECVAYLI or other immunotherapies against a control arm of lenalidomide + dexamethasone in patients with high-risk smoldering multiple myeloma (SMM).^1,2
  • Nadeem et al (2023)¹ presented the initial efficacy and safety results from the first 19 enrolled patients with high-risk SMM in the Immuno-PRISM study. In the 12 patients treated with TECVAYLI, the overall response rate (ORR) was 100%. No dose-limiting toxicities (DLTs) were observed in the safety run-in (SRI) cohort. Cytokine release syndrome (CRS) was reported in 58% of TECVAYLI patients and no patients experienced immune effector cell-associated neurotoxicity syndrome (ICANS).

cLINICAL daTA - IMMUNO-PRISM STUDY

Immuno-PRISM (clinicaltrials.gov identifier NCT05469893) is a multi-arm, randomized, phase 2 platform study investigating the efficacy of TECVAYLI or other immunotherapies against a control arm of lenalidomide + dexamethasone in patients with high-risk SMM.^1,2

Study Design/Methods

• Key eligibility criteria
  • High-risk SMM defined as having 1 of the following 2 criteria^1,2:
    • International Myeloma Working Group (IMWG) high risk per “20-2-20” criteria, defined as presence of any 2 of the following:
      • Serum M spike ≥2 g/dL, involved-to-uninvolved free light chain (FLC) ratio ≥20, bone marrow plasma cells (BMPCs) ≥20%.
    • OR an IMWG total score of 9 using the following scoring system:
      • FLC ratio: >10-25=2, >25-40=3, >40=5.
      • Serum M-Protein (g/dL): >1.5-3=3, >3=4.
      • BMPC (%): >15-20=2, >20-30=3, >30-40=5, >40=6.
      • Fluorescence In Situ Hybridization (FISH) abnormality (t[4,14], t[14,16], 1q gain, or del13q)=2.
  • Presence of ≥10% BMPCs and at least 1 of the following^1,2:
    • Evolving pattern: evolving Monoclonal Protein (eMP) (≥10% increase in monoclonal protein/immunoglobulin [Ig]) within the first 6 months (only if M-protein ≥3 g/dL) and/or ≥25% increase in M-protein/Ig within the first 12 months, with a minimum required increase of 0.5 g/dL in M-protein and/or 500 mg/dL in Ig.
    • Abnormal plasma cell immunophenotype (≥95% of BMPCs are clonal) and reduction of ≥1 uninvolved Ig isotype (only IgG; IgA and IgM will be considered).
    • High-risk cytogenetics defined as presence of t(4;14), t(14;16), t(14;20), 17p deletion, TP53 mutation, or 1q21 gain.
• Exclusion criteria: presence of SLiM-CRAB criteria for active multiple myeloma, diagnosed or treated for another malignancy within 2 years of enrollment, prior SMM directed therapy administered within 6 months of beginning treatment, stroke or seizure within 6 months, or uncontrolled intercurrent illnesses including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.^1,2
• Primary endpoint: complete response rate (CRR).^1,2
• Key secondary endpoints: safety, progression free survival (PFS), minimal residual disease (MRD) negativity, ORR, overall survival.^1,2
• SRI: safety was established by using a SRI method to enroll 6 patients directly into the TECVAYLI arm.^1,2
  • The first 3 patients received a lower than recommended phase 2 dose (RP2D) of TECVAYLI 0.72 mg/kg weekly (cycle 1).
  • The next 3 patients received the RP2D of TECVAYLI 1.5 mg/kg weekly (cycle 1).
• Dosing: once safety was established, patients were randomized 1:2 into one of the following arms (study treatment will continue as long as there are disease benefits from the study drugs or for a maximum of 24 months)^1,2:
  • Lenalidomide and dexamethasone (n=15)
  • TECVAYLI (n=30)
    • After screening, patients received 2 step-up doses (SUDs) of TECVAYLI: 0.06 mg/kg on day 1 and 0.3 mg/kg on day 3 of cycle 1.
    • Following step-up dosing, patients received TECVAYLI 1.5 mg/kg once weekly (QW) in cycles 1-2, TECVAYLI 3 mg/kg once every other week (Q2W) in
      cycles 3-6, and TECVAYLI 3 mg/kg once every 4 weeks (Q4W) in cycles 7-24.
  • After 4 cycles, patients had the option of stem-cell collection.

Nadeem et al (2023)¹ presented the initial efficacy and safety results from the first 19 enrolled patients with high-risk SMM in the Immuno-PRISM study.

Results

Treatment Disposition, Baseline Demographics, and Disease Characteristics

• Baseline patient characteristics are presented in Table: Immuno-PRISM Study: Patient Characteristics.

Efficacy

• Efficacy outcomes for patients who received TECVAYLI are detailed in Table: Immuno-PRISM Study: Efficacy-Response in the TECVAYLI arm.
• No patients progressed while on TECVAYLI treatment.
• Stem-cell collection was successful in all eligible patients (average stem cell yield of 8.94 x 10⁶ CD34⁺ cells/kg).

Safety

• No DLTs were observed in the SRI cohort.
• The hematologic adverse events (AEs) of grade 3 or higher were grade 4 neutropenia in 21% of patients (4/19) and grade 4 thrombocytopenia in 1 patient (5%). All grade 3 or higher toxicities resolved.
• Grade 3 or higher non-hematologic AEs observed in the first 19 enrolled patients were grade 3 increased alanine aminotransferase (ALT) in 3 patients (16%) and grade 3 diarrhea in 1 patient (5%). All grade 3 or higher toxicities resolved.

Cytokine Release Syndrome

• Out of the 12 patients treated with TECVAYLI, CRS was reported in 7 patients (58%). Grade 1 CRS was reported in 7 patients and grade 2 CRS was reported in 2 patients (which required tocilizumab). No patients had grade 3 or greater CRS.

Neurotoxicity

• Out of the 12 patients treated with TECVAYLI, no patients experienced ICANS, and no delayed neurotoxicity was observed.

Infections

• A summary of the incidence and types of grade 2 or higher infections are provided in Table: Immuno-PRISM Study: Infections in the TECVAYLI arm (Grade 2 or Higher).¹
• All patients with hypogammaglobulinemia, treated with TECVAYLI, received intravenous immunoglobulin (IVIG).
  • Prior to IVIG initiation, mean IgG levels were 418 mg/dL. Normalization of IgG levels within 2 doses of IVIG was achieved in 64% of patients.

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 06 March 2025.