SUMMARY

• MajesTEC-1 (MMY1001) is a phase 1/2, multicohort study evaluating the safety and efficacy of TECVAYLI in patients with relapsed or refractory multiple myeloma (RRMM). Cohort A (triple-class exposed) evaluated the safety and efficacy of TECVAYLI in RRMM after prior exposure to a proteasome inhibitor (PI), an immunomodulatory agent, and an anti-CD38 monoclonal antibody.^1-8
  • Moreau et al (2021)¹ presented the primary efficacy and safety results from the phase 1/2 MajesTEC-1 study Cohort A at a median follow-up of 7.8 months. The overall response rate (ORR) was 62.0% in the efficacy analysis population [N=150]). The most common adverse events (AEs; any grade) were cytokine release syndrome (CRS; 71.5%) and neutropenia (65.5%).
  • Garfall et al (2024)⁶ presented longer-term efficacy and safety results from the phase 1/2 MajesTEC-1 study Cohort A at a median follow-up of 30.4 months. The ORR was 63.0%. The most commonly reported treatment-emergent adverse events (TEAEs; any grade) were infections (78.8%), CRS (72.1%), and neutropenia (71.5%).
• Costa et al (2024)^9,10 presented results from subgroup analyses evaluating efficacy and safety outcomes in patients by prior lines of therapy (LOT) and in patients with high-risk (HR) features in the MajesTEC-1 study.
• van de Donk et al (2024)^11,12 conducted a post hoc analysis that evaluated the potential impact of coronavirus disease 2019 (COVID-19) on outcomes in patients receiving the recommended phase 2 dose (RP2D) of TECVAYLI in the MajesTEC-1 study. At a median follow-up of 22.8 months, any grade and grade 3/4 COVID-19 infection were reported in 29.1% (n=48) and 21.2% (n=35) of patients, respectively and deaths due to COVID-19 infection were reported in 10.9% of patients (n=18).
• Usmani et al (2023)¹³ presented efficacy and safety data for 63 patients who switched from weekly (QW) to a less frequent dosing interval of TECVAYLI (every other week [Q2W] or every 4 weeks [Q4W]) in the MajesTEC-1 study. At a median follow-up of 12.6 months (range, 1-25), the median duration of response (DOR) was not reached in patients who received TECVAYLI at less frequent dosing intervals.
• Moreau et al (2022)³ published pharmacokinetic (PK), immunogenicity and biomarker data for patients receiving TECVAYLI in the MajesTEC-1 study at a median follow-up of 14.1 months (range, 0.3-24.4).
• Frerichs et al (2024)¹⁴ evaluated the impact of TECVAYLI RP2D on humoral immunity in patients with RRMM in the MajesTEC-1 study.
• Martin et al (2024)¹⁵ reported patient-reported outcomes (PROs) in 125 patients from phase 2 of the MajesTEC-1 study. Health-related quality of life (HRQoL) reported, generally, an increase in the proportion of patients reporting clinically meaningful improvements from baseline for all scales of the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) (≥10 points) and EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) (≥7 points) questionnaires.
• Other relevant data have been identified in addition to the data summarized above:
  • Matous et al (2024)¹⁶ presented results from an evaluation of higher step-up doses (SUDs) on CRS in 2 exploratory phase 1 cohorts from MajesTEC-1 (Cohort 22: SUDs of 0.1 mg/kg and 0.5 mg/kg or Cohort 23: SUDs of 0.2 mg/kg and 0.7 mg/kg). At a median follow-up of 10.2 months for Cohort 22 and 3.2 months for Cohort 23, a total of 22 CRS events were reported in 16 patients (8 patients in each cohort; all grade 1/2). Median onset of CRS through Cycle 1 Day 1 was 2.0 days in Cohort 22 and 2.5 days in Cohort 23; median CRS duration was 2 days in both cohorts. Recurrent CRS was reported in 2 patients in each cohort. All patients received supportive therapy. Tocilizumab was given to 5 patients (62.5%) in Cohort 22 and 4 patients (50.0%) in Cohort 23. All CRS events resolved. No cases of immune effector cell-associated neurotoxicity syndrome (ICANS) were reported.

CLINICAL DATA - majestec-1 study - cohort a

MajesTEC-1 (MMY1001; clinicaltrials.gov identifiers: NCT03145181; NCT04557098) is evaluating the safety and efficacy of TECVAYLI in patients with RRMM.^1-8

• Cohort A of the MajesTEC-1 study evaluated the efficacy and safety of TECVAYLI in 165 patients with RRMM after ≥3 prior LOT, including triple-class exposure to a PI, an immunomodulatory drug and an anti-CD38 monoclonal antibody. Of the 165 patients enrolled in the RP2D Cohort, 40 patients were enrolled in phase 1 and 125 patients were enrolled in phase 2.³

Study Design/Methods

• The main objectives of MajesTEC-1 are as follows: Part 1 (dose escalation) to determine the RP2D for TECVAYLI; Part 2 (dose expansion) to distinguish safety and tolerability of TECVAYLI at the RP2D; Part 3 (the phase 2 component) to evaluate the efficacy of TECVAYLI at the RP2D.^2,3,17
• Key eligibility criteria: ≥18 years of age, documented RRMM per International Myeloma Working Group (IMWG) criteria, ≥3 prior lines of treatment including a PI, an immunomodulatory drug, and an anti-CD38 monoclonal antibody, Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.^3,17
• Key exclusion criteria¹⁷:
  • B-cell maturation antigen (BCMA) therapy, targeted therapy, epigenetic therapy, or treatment with an investigational drug or use of an invasive investigational medical device within 21 days or at least 5 half-lives, whichever is less.
  • Monoclonal antibody or cytotoxic therapy within 21 days.
  • PI therapy within 14 days.
  • Immunomodulatory drug therapy within 7 days.
  • Gene-modified adoptive cell therapy (eg, chimeric antigen receptor modified T cells, natural killer cells) within 3 months.
  • Radiotherapy within 14 days or focal radiation within 7 days.
  • Vaccination with live, attenuated vaccine within 4 weeks prior to the first dose of TECVAYLI, during treatment, and for 30 days after the last dose of TECVAYLI, unless first discussed with sponsor.
  • Received a cumulative dose of corticosteroids equivalent to ≥140 mg of prednisone within 14 days prior to first dose of TECVAYLI (does not include pretreatment medication).
  • Allogeneic stem cell transplant within 6 months before the first dose of TECVAYLI (patient who received an allogeneic transplant must be off all immunosuppressive medications for 6 weeks without signs of graft-versus-host disease) or autologous stem cell transplant within 12 weeks before the first dose of TECVAYLI.
• Primary endpoint: ORR (defined as partial response or better [≥PR] according to IMWG criteria).^3,4
• Key secondary endpoints: DOR, very good partial response or better (≥VGPR), complete response or better (≥CR), stringent complete response (sCR), time to response, minimal residual disease (MRD) status, progression-free survival (PFS), overall survival (OS), safety, PK, immunogenicity, and PROs.^3,4
• Exploratory endpoints: soluble BCMA levels, cytokines, and T-cell activation markers.³
• Dosing:
  • Step-up doses of TECVAYLI (0.06 mg/kg and 0.3 mg/kg subcutaneously [SC]) were administered 2-4 days apart and completed 2-4 days prior to the first full treatment dose of TECVAYLI 1.5 mg/kg SC.³
  • Subsequent treatment doses: TECVAYLI 1.5 mg/kg SC QW until progressive disease or unacceptable toxicity.^3,4
  • The option to switch to Q2W if patients achieved the following response:
    • Phase 1: ≥PR for ≥4 cycles.^4,13
    • Phase 2: ≥CR for ≥6 months.^4,13
  • Patients could then switch to Q4W dosing if they exhibited continued response on the Q2W schedule.^4,13
  • Premedications: dexamethasone, acetaminophen, and diphenhydramine were required to be administered for each step-up dose and the first full treatment dose of TECVAYLI.³
• Patients were required to be hospitalized for at least 48 hours from the start of the injection, for each step-up dose and the first full treatment dose of TECVAYLI.¹⁷

PRIMARY EFFICACY AND SAFETY ANALYSIS

Moreau et al (2021)¹ presented the primary efficacy and safety results from the phase 1/2 MajesTEC-1 study Cohort A at a median follow-up of 7.8 months (range, 0.5-18).

Results

Treatment Disposition

• At clinical data cutoff, the median treatment duration was 5.9 months (range, 0.2-18.0) for the primary safety analysis set (N=165). Of these patients, 46.7% (n=77) received treatment for ≥6 months and 16.4% (n=27) received treatment for ≥9 months. There were no TECVAYLI dose reductions.
• The pivotal Cohort included 165 patients. The phase 1 RP2D Cohort included 40 patients; of these, 20 patients continued TECVAYLI treatment and 20 discontinued due to progressive disease (n=16), physician decision (n=3), or patient withdrawal (n=1).
• In the phase 2 RP2D Cohort (n=125), 75 patients continued treatment and 50 patients discontinued due to progressive disease (n=29), death (n=9), physician decision (n=7), patient withdrawal (n=4), or AE (n=1).
• Baseline characteristics and demographics for Cohort A are presented in Table: MajesTEC-1 Study (Cohort A): Baseline Characteristics and Demographics.

Efficacy

Response Rates

• At a median follow-up of 7.8 months (range, 0.5-18), the ORR was 62% (95% confidence interval [CI], 53.7-69.8). Details are provided in Table: MajesTEC-1 Study (Cohort A): Response Rates in the Efficacy Analysis Subset.
  • ORR was consistent in the high cytogenetic risk, triple-class refractory, and penta-drug refractory subgroups.
• The median time to first response was 1.2 months (range, 0.2-5.5).

MRD Negativity

• MRD negativity rate at 10^-5 threshold was 24.7% (95% CI, 18.0-32.4; n=37).
• MRD negativity rate at 10^-6 threshold was 16.7% (95% CI, 11.1-23.6; n=25).
• MRD negativity rate was 41.9% in patients who achieved ≥CR.

Duration of Response

• The median follow-up for responders (n=93) was 8.0 months (range, 2.4-18.0), with 91.4% of patients having at least 6 months of follow-up.
• Median DOR and OS was not reached.
• For responders (n=93), the event-free rate was 92.5% (95% CI, 80.6-97.2) at 6 months and 85.9% (95% CI, 70.0-93.7) at 9 months.
• The 6-month PFS rate was 64.4% (95% CI, 56.0-71.7), and 9-month PFS rate was 58.5% (95% CI, 48.8-67.0).
• Of the responders, 82 patients were alive without disease progression or subsequent treatment, 11 patients had progressed or died, and 1 patient (no longer on treatment) continued to respond.
• Nineteen patients changed to less frequent dosing.

Safety

• AEs reported in ≥20% of patients in the safety analysis set are presented in Table: MajesTEC-1 Study (Cohort A): AEs (≥20%) in the Safety Analysis Set.
• Serious adverse events (SAEs) were reported in 53.3% (n=88) of patients; investigator-assessed TECVAYLI-related SAEs were reported in 33 patients.
• A total of 63% of patients (n=104) reported infections (grade 3/4, 35.2%; opportunistic, 5.5% [n=9]).
• Hypogammaglobulinemia was observed in 72.1% of patients (n=119), with 41% of patients receiving intravenous immunoglobulin (IVIG) during the study.
• A total of 9 deaths due to AEs were reported; none were related to TECVAYLI (COVID-19, n=7; hemoperitoneum, n=1; pneumonia, n=1).
• No patients required dose reduction, including those who had neurotoxic events.
• One patient discontinued TECVAYLI due to adenoviral pneumonia; no treatment discontinuations due to CRS or neurotoxicity were reported.

Cytokine Release Syndrome

• Of the 71.5% all-grade CRS events reported, most were grade 1 (49.7%) or grade 2 (21.2%). One transient grade 3 CRS event was reported, which resolved.
• CRS events were limited to the step-up dosing phase and cycle 1 in 97% of cases. For detailed parameters as well as mitigation strategies used for CRS, see Table: MajesTEC-1 Study (Cohort A): CRS.
• More than 1 tocilizumab dose was given to 2.4% of patients for a single CRS event.
• All CRS events resolved; no treatment discontinuations due to CRS were reported.

Neurotoxicity

• Headache (8.5%) was the most commonly reported neurotoxic event. Additional details and supportive measures used for neurotoxicity are presented in Table: MajesTEC-1 Study (Cohort A): Neurotoxicity.
• No grade ≥3 neurotoxicity AEs were reported.

PK and Immunogenicity

• TECVAYLI SC 1.5 mg/kg maintained exposure over the max EC₉₀.
• At the RP2D, no patients developed anti-teclistamab antibodies (n=146).

LONG-TERM EFFICACY AND SAFETY ANALYSES

Moreau et al (2022)³ published efficacy and safety results from the MajesTEC-1 study at a median follow-up of 14.1 months. van de Donk et al (2023)^4,5,18 presented updated efficacy and safety results from the MajesTEC-1 study at a median follow-up of 23 months. Martin et al (2023)¹⁹ published a detailed overview of incidence and management of CRS with TECVAYLI in the MajesTEC-1 study. Nooka et al (2024)²⁰ published the incidence, timing, and management of infections in patients receiving TECVAYLI in the MajesTEC-1 study at a median follow-up of 22.8 months. Garfall et al (2024)⁶ presented long-term efficacy and safety results from the MajesTEC-1 study at a median follow-up of 30.4 months. The results for the latest follow-up are summarized below.

Results

Treatment Disposition

• At a median follow-up of 30.4 months, 165 patients had received TECVAYLI at the RP2D. Of these, 65 patients had transitioned to less frequent dosing (eg, Q2W).
  • At the data cutoff of August 22, 2023, 38 patients remained on treatment (37 patients remained on a less frequent dosing schedule).

Efficacy

Response Rates

• At a median follow-up of 30.4 months, ORR was 63.0%. Additional details are provided in Table: MajesTEC-1 Study (Cohort A): Summary of ORR.

MRD Negativity

• Overall, 85.7% of MRD-evaluable patients (48/56) achieved MRD negativity at a threshold of 10⁵; 56.1% of patients (23/41) sustained MRD negativity for ≥6 months, and 38.9% of patients (14/36) sustained MRD negativity for ≥12 months.

Durability of Response

• DOR, PFS, and OS in select patient subgroups are summarized in Table: MajesTEC-1 Study (Cohort A): DOR, PFS, and OS in Select Patient Subgroups.

Safety

• At a median follow-up of 30.4 months, no new safety signals were reported.
• TEAEs occurring in ≥20% of patients are summarized in Table: MajesTEC-1 Study (Cohort A): Summary of TEAEs (≥20%).
• No new cases of CRS or immune effector cell-associated neurotoxicity syndrome (ICANS) were reported at the 30.4-month follow-up.
• A total of 22 deaths due to infection were reported, of which 18 deaths were due to COVID-19.
  • No new deaths due to COVID-19 TEAEs were reported since the 22.8-month follow-up.
• TEAEs leading to dose reduction were reported in 1 patient (0.6%) and TEAEs leading to discontinuation were reported in 8 patients (4.8%); 5 discontinuations were due to infection.

CLINICAL DATA - majestec-1 study - SUbGROUP ANALYSES

Costa et al (2024)⁹ presented a subgroup analysis evaluating the efficacy and safety of TECVAYLI in patients who received 2-3 prior LOT vs patients who received ≥4 prior LOT at a follow-up of 30.4 months.

Results

Baseline Characteristics

• At a median follow-up of 30.4 months 22.6% of patients (n=43) had received ≤3 prior LOT and 74% of patients (n=122) had received >3 prior LOT.
• Patient characteristics are provided in Table: MajesTEC-1 Study (Cohort A): Baseline Characteristics in Patients by Number of Prior LOT.

Efficacy

• Response rates in patients by the number of prior LOT are presented in Table: MajesTEC-1 Study (Cohort A): Efficacy Outcomes in Patients by Number of Prior LOT.

Safety

• A summary of safety outcomes in patients by number of prior LOT is provided in Table: MajesTEC-1 Study (Cohort A): Summary of Safety Outcomes in Patients by Number of Prior LOT.

Costa et al (2024)¹⁰ presented a subgroup analysis evaluating efficacy and safety outcomes in patients with HR features from the MajesTEC-1 study.

Results

Baseline Characteristics

• At a data cutoff of Aug 22, 2023, a total of 165 patients had received TECVAYLI at the RP2D. Patient characteristics are provided in Table: MajesTEC-1 Study (Cohort A): Baseline Characteristics of Patients With HR Features.
• HR features evaluated included the following:
  • Penta-drug refractory (≥2 PIs, ≥2 immunomodulatory drugs, and ≥1 anti-CD38 monoclonal antibodies), HR cytogenetics (del[17p], t[4:14], t[14;16]), age ≥75 years, bone marrow plasma cells (BMPCs) ≥60%, extramedullary disease (EMD; ≥1 soft tissue plasmacytoma with no contact with bony structures, a stricter definition than used in other clinical trials), International Staging System (ISS) stage III.

Efficacy

• Select efficacy outcomes including response rates and DOR were evaluated. Response rates in patients with HR features are presented in Table: MajesTEC-1 Study (Cohort A): Summary of ORR in Patients With HR Features. Details on DOR in patients with HR features are provided in Table: MajesTEC-1 Study (Cohort A): DOR to TECVAYLI in Patients With HR Features.

Safety

• A summary of safety outcomes in patients with HR features is provided in Table: MajesTEC-1 Study (Cohort A): Summary of Safety Outcomes in Patients With HR Features.

impact of COVID-19 on outcomes in MajesTEC-1 Study (COHORT A)

van de Donk et al 2024^11,12 conducted a post hoc analysis that evaluated the potential impact of COVID-19 on outcomes in patients receiving the RP2D of TECVAYLI in the MajesTEC-1 study (data cutoff date January 4, 2023). Of note, MajesTEC-1 recruitment occurred concurrently with the pandemic, starting in March of 2020. COVID-19 vaccines were not approved until late 2020 to early 2021, approximately 9 months into MajesTEC-1 enrollment.

Methods

• Infections (including COVID-19) were managed per institutional guidelines and/or TECVAYLI interruption; annual inactivated influenza and COVID‐19 vaccinations (including booster doses) were recommended per availability.
• Patients with grade 5 COVID-19 infection were censored at the time of the last disease evaluation for analyses of PFS (n=17) and DOR (n=13) if death occurred without disease progression. All patients who died from COVID-19 (n=18) were censored at the time of death for analysis of OS.
• Outcomes were analyzed in all patients, in patients with ≥CR, by the number of prior LOT (≤3 or >3), and in a phase 2 efficacy population of 110 patients enrolled by March 18, 2021.

Results

Treatment Disposition, Baseline Characteristics, and Disease/Treatment Characteristics

• At a median follow-up of 22.8 months, a total of 165 patients with RRMM who were treated with TECVAYLI were included in this analysis.
• Patients had a mean age of 64 years (range, 33-84) and received a median of 5 prior LOT (range, 2-14).
• At study entry, 77.6% of patients were triple-class refractory and 30.3% were penta- drug refractory (≥2 immunomodulatory drugs, ≥2 PIs, and ≥1 anti-CD38 antibody).

Safety

• Any-grade and grade 3/4 COVID-19 infection was reported in 29.1% (n=48) and 21.2% (n=35) of patients, respectively, and deaths due to COVID-19 infection were reported in 10.9% of patients (n=18); 4 deaths from COVID-19 were considered by the investigators to be related to TECVAYLI treatment.
• Supportive therapies (including glucocorticoids, anti-infectives, hyperimmune plasma, and tocilizumab) were used to treat COVID-19 in 24.2% of patients. Antivirals (remdesivir) were used in 9.1% of patients.
• TECVAYLI administration was interrupted in 17.6% (n=29) of patients.
• A total of 7.9% of patients (n=13), including 1/18 patients who died of COVID-19, were vaccinated at least once with a COVID-19 vaccine before TECVAYLI was administered. The patient who died received 2 doses before starting TECVAYLI.
• A total of 60% of patients (n=99), including 13/18 patients who died of COVID19, were vaccinated at least once with a COVID-19 vaccine on study overall (1 dose, n=3; 2 doses, n=4; 3 doses, n=3; 4 doses, n=3 [the patient who was vaccinated pre-TECVAYLI received their 3^rd dose on-study]).
• Patients who never received a COVID-19 vaccination tended to die of COVID-19 earlier during TECVAYLI treatment (range, 0.7-5.9 months) compared to patients who received ≥1 COVID-19 vaccination (range, 2.4-25.9 months). A greater proportion of deaths occurred in 2021 (5/5 vs 5/13 respectively) compared to 2022 (0/5 vs 8/13, respectively).

Impact of COVID-19 on Efficacy Outcomes

• At a median follow-up of 22.8 months, when data for COVID-19 deaths were censored, prolonged median PFS, OS, and DOR were observed compared with the overall MajesTEC-1 analysis.
• The median PFS, OS, and DOR with TECVAYLI in the RP2D Cohort of MajesTEC-1 overall analysis and when censored for COVID-19 deaths are presented in Table: MajesTEC-1 Study (Cohort A): Efficacy Outcomes After Overall Analysis and When Censored for COVID-19 Deaths.

Dosing Interval Adjustment in MajesTEC-1 Study (Cohort A)

Usmani et al 2023¹³ assessed efficacy and safety in 63 patients who switched to a less frequent dosing interval of TECVAYLI (Q2W or Q4W) in the MajesTEC-1 study.

Study Design/Methods

• In addition to the study design outlined earlier; patients had the option to switch to Q2W if they achieved the following response:
  • Phase 1: ≥PR for ≥4 cycles.
  • Phase 2: ≥CR for ≥6 months.
• Patients could then switch to Q4W dosing if they exhibited continued response on the Q2W schedule.

Results

Treatment Disposition

• At a median follow-up of 23 months, 165 patients were treated at TECVAYLI RP2D, with 104 patients achieving a response. Among these responders, 63 patients were switched to TECVAYLI Q2W dosing (Phase 1, n=22; Phase 2, n=41). Of these, 9 patients continued to TECVAYLI Q4W dosing.
  • Among the 63 patients who switched to Q2W dosing, 54 patients were eligible to switch to Q2W dosing per protocol. Additionally, 9 patients who switched were ineligible per protocol (AEs, n=3; other reasons, n=6).
  • The median time to switch from the first TECVAYLI QW dose to the first Q2W dose was 11.3 months (range, 3-30; median 6.8 months in Phase 1; 12.7 months in Phase 2).
• See Table: MajesTEC-1 Study (Cohort A): Baseline Characteristics of Patients Who Switched to Q2W or Q4W Dosing for additional details.

Efficacy

• At the time of switching, 54 patients (85.7%) were in ≥CR, 8 patients were in ≥VGPR, and 1 patient had a PR.
• The median follow-up for patients after switching to TECVAYLI Q2W dosing or Q4W, was 12.6 months (range, 1-25).
• The median DOR was not reached. Among the patients that switched, 68.7% of patients (95% CI, 53.6-79.7) observed a durable response for ≥2 years since the first response.

Safety

• Five deaths occurred (4 due to COVID-19).

Infections

• The incidence of Grade ≥3 treatment-emergent infections was 15.6% in patients who switched to TECVAYLI Q2W dosing by 1 year.
• The incidence of Grade ≥ 3 treatment-emergent infections was 33.3% in patients who continued TECVAYLI QW dosing by 1 year.

Pharmacokinetics and Immunogenicity in MajesTEC-1 Study (Cohort A)

Moreau et al 2022³ published PK, immunogenicity and biomarker data for patients receiving TECVAYLI in the MajesTEC-1 study at a median follow-up of 14.1 months (range, 0.3-24.4).

• No patients treated at RP2D of TECVAYLI developed anti-teclistamab antibodies (n=146).
• As a potential marker of tumor burden and response, serum levels of soluble BCMA were assessed in 59 patients who had a ≥PR within the first month of study treatment. Of these 59 evaluable patients, 68% (n=40) observed rapid decreases in total levels of soluble BCMA.

Impact on Humoral Immunity in MajesTEC-1 Study (Cohort A)

Frerichs et al 2024¹⁴ evaluated the impact of the TECVAYLI RP2D on polyclonal immunoglobulin (Ig) and B-cell counts in patients with RRMM (N=135) in the MajesTEC-1 study.

• TECVAYLI therapy eliminated normal plasma cells in ex vivo assays, induced rapid depletion of peripheral blood B cells, and reduced the levels of polyclonal immunoglobulin G (IgG), IgA, IgE, and IgM without recovery over time.
• Response to vaccines against Streptococcus pneumoniae (n=17; 7.1% response rate), Haemophilus influenzae type B (n=17; 5.9% response rate), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; n=13; none of the patients had a
  vaccine-induced anti-spike IgG response) was severely impaired in patients treated with TECVAYLI versus the observed vaccination response in patients with newly diagnosed multiple myeloma or RRMM.
• The impact of IVIG supplementation on risk of infections was analyzed in 52 patients. Of note, prophylactic IVIG significantly lowered the risk of serious infections among patients treated with TECVAYLI (cumulative incidence of infections at 6 months: 5.3% in the IVIG group vs 54.8% in the observation-only group [P<0.001]).

Patient-Reported Outcomes in MajesTEC-1 Study (Cohort A)

Martin et al 2024¹⁵ reported PRO data from 125 patients enrolled in phase 2 Cohort of MajesTEC-1, based on a clinical cutoff date of March 16, 2022. HRQoL was assessed using the EORTC QLQ-C30 and EQ-5D-5L questionnaires.

• Generally, there was an increase in the proportion of patients reporting clinically meaningful improvements from baseline over time for all scales of the EORTC QLQ-C30 (≥10 points) and EQ-5D-5L (≥7 points) questionnaires.
  • At cycle 12, clinically meaningful improvements were reported by 50% of patients for pain and fatigue. Meaningful improvements were reported by 8% of patients for nausea and vomiting, and 49% of patients for global health status.
  • At cycles 2-12, changes in the EQ-5D-5L visual analog scale (VAS) scores indicated improvement in general health, with >50% of patients showing an overall improvement from cycle 10 onwards.
  • Clinically meaningful worsening symptoms generally decreased in patients for all scales of the EORTC QLQ-C30 and EQ-5D-5L VAS scores over time.
  • At all time points, clinically meaningful worsening of pain, nausea, and vomiting was reported in <40% of patients and that of fatigue in <50% of patients at cycles 4 through 12.
  • At cycle 12, clinically meaningful worsening of pain, fatigue, and nausea and vomiting was reported in <25% of patients.
• From baseline, scores for emotional functioning showed an improvement at all timepoints. From baseline to cycle 2, scores for physical functioning and role functioning initially worsened but later showed improvement by cycles 6 (role functioning) and 8 (physical functioning). Little change was observed in cognitive and social functioning during the study.
  • Across the subgroups, patients reaching ≥CR, VGPR, or PR showed similar trends of improvement in emotional, physical, and role functioning scores, and little change from baseline in cognitive and social functioning.

Literature Search

A literature search of Ovid MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File databases (and/or other resources, including internal/external databases) was conducted on 09 December 2024.