SUMMARY

• TECVAYLI is not approved by the regulatory agencies for the treatment of patients with high-risk smoldering multiple myeloma (SMM). 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 multiple arm, randomized, phase 2 platform study investigating the efficacy of TECVAYLI or other immunotherapies against a control arm of lenalidomide and dexamethasone combination in participants with high-risk SMM.^1,2
  • Nadeem et al (2023) presented (at the 65th American Society of Hematology [ASH] Annual Meeting) the initial efficacy and safety results in the first 19 enrolled patients with high-risk SMM.¹

cLINICAL daTA - IMMUNO-PRISM STUDY

Immuno-PRISM (clinical trials.gov identifier NCT05469893) is a multiple arm, randomized, phase 2 platform study investigating the efficacy of TECVAYLI or other immunotherapies against a control arm of lenalidomide and dexamethasone combination in patients with high-risk smoldering multiple myeloma.^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 two of the following:
      • Serum M spike ≥2 gm/dL, involved to uninvolved free light chain (FLC) ratio ≥20, bone marrow plasma cell (BMPC) % ≥20%.
    • OR a 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% BMPC and at least one 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/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 immunoglobulin 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, 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 in study, stroke or seizure within 6 months, 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, overall response rate (ORR), overall survival.^1,2
• Safety run-in: safety was established by using a safety run-in 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 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, TECVAYLI 3 mg/kg once every 4 weeks (Q4W) in cycles 7-24.
  • After 4 cycles, patients had the option of stem cell collection.

Results

Initial efficacy and safety results of the first 19 enrolled patients with high-risk SMM are summarized below.¹

Patient characteristics

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

Efficacy

• Efficacy outcomes for patients who received TECVAYLI are detailed in Table: Immuno-PRISM: Efficacy - Response.
• No patients progressed while on TECVAYLI treatment.¹
• Stem-cell collection was successful in all eligible patients (average stem cell yield of 8.94 x 10⁶ CD34+ cells/kg).¹

Safety

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

Cytokine Release Syndrome (CRS)

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

Neurotoxicity

• Out of the 12 patients treated with TECVAYLI, no patients experienced immune effector cell-associated neurotoxicity syndrome (ICANS) and no delayed neurotoxicity was observed.¹

Infections

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

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 22 March 2024.