TECVAYLI - Use in High-Risk Smoldering Multiple Myeloma

SUMMARY

• Johnson & Johnson does not recommend the use of TECVAYLI in a manner that is inconsistent with the approved labeling.
• TECVAYLI is not approved by the regulatory agencies for the treatment of patients with high-risk smoldering multiple myeloma (SMM).
• 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 SMM.^1-3
  • Nadeem et al (2026)² presented efficacy and safety results from the phase 2 Immuno-PRISM study evaluating TECVAYLI vs lenalidomide + dexamethasone in patients with high-risk SMM. Among 45 TECVAYLI-treated patients, 75.6% achieved a complete response or better (≥CR) and 86.7% achieved a very good partial response or better (≥VGPR). Minimal residual disease (MRD) negativity at a sensitivity threshold of 10^-5 was achieved in 82% of patients, and the 2-year estimated progression-free survival (PFS) rate was 92%. Cytokine release syndrome (CRS) occurred in 71.1% of TECVAYLI-treated patients, with no grade ≥3 events. No patients experienced immune effector cell-associated neurotoxicity syndrome (ICANS).
  • 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. CRS was reported in 58% of TECVAYLI patients and no patients experienced ICANS.

cLINICAL daTA - IMMUNO-PRISM STUDY

Immuno-PRISM (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.^1-3

Study Design/Methods

• Key eligibility criteria
  • High-risk SMM defined as having 1 of the following 2 criteria^1-3:
    • 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^1-3:
    • 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.^1-3
• Primary endpoint: complete response rate (CRR).^1-3
• Key secondary endpoints: safety, PFS, MRD negativity, ORR, overall survival (OS), duration of response (DOR), time to progression (TTP).^1,3
• SRI: safety was established by using a SRI method to enroll 6 patients directly into the TECVAYLI arm.^1-3
  • 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)^2,3:
  • Lenalidomide and dexamethasone (n=20; treatment received by 14 patients [6 patients withdrew consent before treatment initiation]).
  • TECVAYLI (n=40; treatment received by 39 patients [1 patient withdrew consent before treatment initiation]).
    • 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 7-12.
  • After 4 cycles, patients had the option of stem-cell collection.

Nadeem et al (2026)² presented the efficacy and safety results from the phase 2 Immuno-PRISM trial evaluating TECVAYLI vs lenalidomide + dexamethasone in patients with high-risk SMM.

Results

Baseline Demographics, and Disease Characteristics

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

Efficacy

• Response outcomes for patients who received TECVAYLI are detailed in Table: Immuno-PRISM Study: IMWG Response.
• Among TECVAYLI-treated patients, 3 were primary non-responders, 3 remained on treatment after achieving a partial response (PR), and 2 attained a complete response (CR) but remained MRD-positive by next-generation sequencing (NGS).
• MRD negativity
  • The median time to MRD negativity was 6.2 months. At this time point, MRD negativity by NGS was achieved in 82% (37/45) of TECVAYLI-treated patients at a sensitivity threshold of 10^-5 and 78% (35/45) at a sensitivity threshold of 10^-6, see Table: Immuno-PRISM Study: MRD Negativity in TECVAYLI-Treated Patients.
  • No cases of MRD negativity at a sensitivity threshold of 10^-5 were reported among patients receiving lenalidomide + dexamethasone.
  • Sustained MRD negativity through the latest available assessment was reported in 100% of the patients (n=28) with serial MRD assessments who were MRD-negative at first assessment.
• At a median follow-up of 23.4 months, PFS was improved with TECVAYLI vs lenalidomide + dexamethasone, see Table: Immuno-PRISM Study: PFS and OS.
• Disease progression by SLiM-CRAB criteria and/or biochemical progression was reported in 8 patients: 3 (7%) in the TECVAYLI arm and 5 (36%) in the lenalidomide + dexamethasone arm.
  • CRAB progression was reported in 5 patients: 2 (4%) in the TECVAYLI arm and 3 (21%) in the lenalidomide + dexamethasone arm.
  • All progression events involved myeloma-related bone disease detected by magnetic resonance imaging (MRI; n=2) or positron emission tomography-computed tomography (PET-CT; n=3).
• TECVAYLI-treated nonresponders: Primary nonresponders (n=3) had disease-burden markers comparable to those of responders, with no baseline B-cell maturation antigen (BCMA) alterations identified; 2 subsequently achieved deep responses to conventional myeloma therapy.

Safety

• CRS was reported in 71.1% of patients receiving TECVAYLI (grade 1, 64.4%; grade 2, 6.7%), with no grade ≥3 events.
• ICANS or neurological toxicities were not reported.
• No difference in grade ≥3 infections was reported between the TECVAYLI and lenalidomide + dexamethasone arms; all TECVAYLI-treated patients received intravenous immunoglobulin (IVIG) prophylaxis.
• Safety outcomes are summarized in Table: Immuno-PRISM Study: Safety Profile.

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 8.94×10⁶ 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 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 03 July 2026.