SUMMARY

• Janssen does not recommend any practices, procedures or usage that deviate from the product labeling or are not approved by the regulatory agencies.
• MajesTEC-1 (MMY1001) is a phase 1/2, multicohort study evaluating the efficacy and safety of TECVAYLI in patients with relapsed or refractory multiple myeloma (RRMM).^1-3
  • Cohort A (triple-class exposed) included 165 patients with RRMM who were previously treated with a proteasome inhibitor (PI), an immunomodulatory agent, and an anti-CD38 monoclonal antibody.³
    • Costa et al (2024)⁴ presented a subgroup analysis of the MajesTEC-1 study, evaluating the efficacy and safety in patients with high-risk (HR) features, including patients ≥75 years of age. As of the data cutoff on August 22, 2023, the overall response rate (ORR) was 63% in all patients and 54.2% in patients ≥75 years of age. Any-grade treatment-emergent adverse events (TEAEs) were reported in 100% of patients ≥75 years of age; 87.5% of TEAEs were grade 3/4.
• Pasvolsky (2024)⁵ presented a retrospective, multicenter study of real-world outcomes of a large cohort of elderly patients (<75 years and ≥75 years) with RRMM receiving standard-of-care (SOC) TECVAYLI treatment.
• Dima et al (2023)⁶ evaluated the efficacy and safety of TECVAYLI in patients >70 years of age compared to those ≤70 years of age in a retrospective, real-world study.
• Dieterle et al (2023)⁷ described the use of TECVAYLI in 3 patients, >80 years of age, with RRMM who received ≥3 prior lines of therapy (LOTs).

CLINICAL DATA - MAJESTEC-1 STUDY

MajesTEC-1 (MMY1001; clinicaltrials.gov identifiers: NCT03145181, NCT04557098) is evaluating the safety and efficacy of TECVAYLI in patients with RRMM.^1-3

Study Design/Methods

• The main objectives are as follows: part 1 (dose escalation), to determine the recommended phase 2 dose (RP2D) for TECVAYLI; part 2 (dose expansion), to distinguish safety and tolerability at RP2D; and part 3 (phase 2 component), to evaluate the efficacy of TECVAYLI at RP2D.^3,8
• Key eligibility criteria:
  • Cohort A: received ≥3 prior LOTs (including a PI, an immunomodulatory drug, and an anti-CD38 mAb) and no prior B-cell maturation antigen (BCMA)-targeted therapy use.³
• Primary endpoint for Cohort A: ORR.³
• Key secondary endpoint for Cohort A: safety.³

Cohort A

Costa et al (2024)⁴ presented a subgroup analysis from the MajesTEC-1 study evaluating the efficacy and safety in patients with HR features. Results specific to patients ≥75 years of age are summarized below.

Results

Treatment Disposition, Baseline Demographics, and Disease Characteristics

• By the data cutoff date of August 22, 2023, a total of 165 patients had received TECVAYLI at the RP2D; 24 patients (14.5%) were aged ≥75 years.

Efficacy

• Select efficacy outcomes, including the response rate and duration of response (DOR), were evaluated. The response rate in the overall population and in patients aged ≥75 years is presented in Table: MajesTEC-1 Study (Cohort A): Summary of ORR. DOR in the overall population and in patients aged ≥75 years is presented in Table: MajesTEC-1 Study (Cohort A): DOR to TECVAYLI.

Safety

• A summary of safety outcomes in the overall population and in patients in patients aged ≥75 years is provided in Table: MajesTEC-1 Study (Cohort A): Summary of Safety Outcomes.

Real-world data

Pasvolsky et al (2024)⁵ presented a retrospective, multicenter study of a large cohort of elderly patients (<75 years and ≥75 years) with RRMM receiving SOC TECVAYLI treatment.

Study Design/Methods

• This retrospective, multicenter study included data of patients with RRMM who received SOC TECVAYLI at 13 centers of the United States (US) Multiple Myeloma Immunotherapy Consortium with a data cutoff date was April 30, 2024.
• Patients included in this study were divided into the following groups: age <75 years and age ≥75 years.

Results

Treatment Disposition, Baseline Demographics, and Disease Characteristics

• A total of 302 patients and 83 patients were included in the <75-year and ≥75-year age groups, respectively. Baseline characteristics of these patients are presented in Table: Baseline Patient Characteristics.

Efficacy

• Overall response was observed in 53% and 62% of patients in the <75-year and ≥75-year age groups, respectively. See Table: Summary of Efficacy Response for additional details.
• Multivariable analysis of the study population is presented in the Table: Multivariable Analysis of Survival Outcomes (<75 Years vs ≥75 Years): PFS and OS.

Safety

• All-grade CRS events were reported in 59% of patients (n=177) in the <75-year age group and in 52% of patients (n=43) in the ≥75-year age group. See Table: Summary of CRS Events for additional details.
• All-grade ICANS events were reported in 13% of patients (n=38) in the <75-year age group and in 19% of patients (n=16) in the ≥75-year age group. See Table: Summary of ICANS Events for additional details.
• Causes of deaths reported in the study population are detailed in Table: Causes of Death.

Dima et al (2023)⁶ presented efficacy and safety data from a retrospective, real-world study evaluating the use of TECVAYLI in older patients (>70 years) with RRMM compared to younger patients (≤70 years).  

Study Design/Methods

• The study population consisted of patients with RRMM who received TECVAYLI as of July 1, 2023 at 5 US academic centers, part of the US Myeloma Innovations Research Collaboration.
• Outcomes assessed included ORR, complete response or better (≥CR), and safety. Responses were assessed using the International Myeloma Working Group (IMWG) criteria.

Results

Treatment Disposition, Baseline Demographics, and Disease Characteristics

• A total of 102 patients were included in the study, including 33 patients (32%), who were >70 years of age and 69 (68%) who were ≤70 years of age.
• Additional baseline characteristics are summarized in Table: Baseline Characteristics.⁴

Efficacy

• At a median follow-up of 3.2 months, ORR (70% vs 61%, P=0.37) and ≥CR (30% vs 28%, P=0.8) were comparable in patients >70 years vs ≤70 years.
• Median estimated progression-free survival was 5.4 vs 3.8 months in patients >70 years vs ≤70 years respectively (P=0.61).

Safety

• Detailed safety data is reported in the Table: Safety Outcomes for Patients >70 years of Age vs Patients ≤70 Years of Age.6

CLINICAL DATA - case reports

Dieterle et al (2023)⁷ reported on the efficacy and safety of TECVAYLI administered at the recommended dosing schedule in patients (N=3) aged >80 years after ≥3 prior LOT. A case report of an octogenarian is summarized below.

• Disease characteristics: An elderly patient (80 years) presented with initial cervical pain and high lambda free serum light chains (FSLCs). The patient fulfilled 3 of 4 CRAB criteria (hypercalcemia, renal dysfunction, anemia, and bone lesions) and was diagnosed with multiple myeloma. Bone marrow biopsy revealed 80% plasma cell infiltration and unfavorable cytogenetics (t[11;14]; monosomy 13; CKS1B gene amplification in 1q21).
• Treatment: After an initial course of radiation, the patient received a first LOT of bortezomib-cyclophosphamide-dexamethasone (5 cycles), a second LOT of daratumumab-lenalidomide-dexamethasone (10 cycles), and a third LOT of daratumumab-pomalidomide-dexamethasone (6 cycles). Prior to TECVAYLI initiation, bridging therapy with cyclophosphamide and dexamethasone was administered to limit disease progression. At the age of 82 years, the patient received step-up doses of TECVAYLI subcutaneously (SC; day 1, 0.06 mg/kg; day 3, 0.3 mg/kg, and day 5, 1.5 mg/kg) in cycle 1. Subsequent TECVAYLI doses (1.5 mg/kg SC weekly) were administered in an outpatient setting.
• Response: The patient achieved complete remission (lambda FSLCs <0.5 mg/L, immunofixation negativity in serum and urine) 1 and 2 months after TECVAYLI initiation.
• Safety: Hematologic adverse events were reported as Grade 1 pancytopenia. No CRS or ICANS events were reported.

Two additional patients >80 years suffering from symptomatic RRMM after proteosome inhibitor, immunomodulatory agent, and anti-CD38 mAb therapy were treated with TECVAYLI. Data on disease characteristics, treatment duration, response, and safety are summarized in the Table: Detailed Patient Characteristics of Octogenarians Treated With TECVAYLI.⁹

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 31 January 2025.