SUMMARY

• Janssen does not recommend the use of TECVAYLI in a manner inconsistent with the approved labeling.
• Infections have been reported as an adverse event (AE) in the MajesTEC-1, MajesTEC-2, MajesTEC-4, MajesTEC-5, MajesTEC-7, RedirecTT-1, and TRIMM-2 studies.^1-15
• MajesTEC-1 is a phase 1/2, multicohort study evaluating the safety and efficacy of TECVAYLI in patients with relapsed or refractory multiple myeloma (RRMM).^1-3,16,17
  • Cohort A (triple-class exposed) included 165 patients who were previously treated with a proteasome inhibitor (PI), an immunomodulatory agent, and an anti-CD38 monoclonal antibody.¹
    • van de Donk et al (2024)^18,19 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. At a median follow-up of 22.8 months, any-grade and grade 3/4 COVID-19 infection was reported in 29.1% and 21.2% of patients, respectively and deaths due to COVID-19 infection were reported in 18 patients.
    • Nooka et al (2023)²⁰ published the incidence, timing, and management of infections in patients receiving TECVAYLI. At a median follow-up of 22.8 months, any grade infections were reported in 80% of patients, with grade 3/4 infections reported in 55.2% of patients.
    • Garfall et al (2024)¹⁷ presented the incidence of infections at a median follow-up of 30.4 months. No new deaths due to COVID-19 treatment-emergent adverse events (TEAEs) were reported since the 22.8-month follow-up.
  • Cohort C included 40 patients previously treated with a PI, an immunomodulatory agent, an anti-CD38 monoclonal antibody and anti-B-cell maturation antigen (BCMA)-targeted therapies.^10,16
    • Touzeau et al (2024)¹⁰ published the incidence of infections at a median follow-up of 28.0 months. Any grade infections were reported in 70% of patients overall. Of these, 32.5% were grade 3/4, and 10% were grade 5.
  • The prophylactic tocilizumab cohort is evaluating the administration of intravenous (IV) tocilizumab (8 mg/kg) prior to TECVAYLI dosing for the reduction of cytokine release syndrome (CRS) in 24 patients.^3,21
    • van de Donk et al (2024)²¹ presented the incidence of infections at a median follow-up of 8.1 months. Any grade infections were reported in 79.2% of patients, with grade 3/4 infections reported in 25.0% of patients.
• MajesTEC-2 is an ongoing, phase 1b, multicohort study evaluating the safety and efficacy of TECVAYLI in combination with other anticancer therapies in patients with multiple myeloma (MM).^4-6,11,22
  • Cohort A included 17 patients with RRMM who received TECVAYLI in combination with DARZALEX FASPRO^® (daratumumab and hyaluronidase) and pomalidomide.¹¹
    • D’Souza et al (2024)¹¹ presented the incidence of infections at a median follow-up of 16.2 months. Any-grade infections were reported in 94.1% of patients, with grade 3/4 infections reported in 64.7% of patients.
  • Cohort C included 28 patients with RRMM who received TECVAYLI and nirogacestat.⁴
    • Offner et al (2023)⁴ presented the incidence of infections at a median follow-up of 14.7 months. The most common infections (≥20%) were COVID-19, pneumonia, bronchitis, and upper respiratory tract infections. The most frequently reported grade 3/4 infection was pneumonia.
  • Cohort D included 31 patients with MM who received TECVAYLI in combination with lenalidomide (Tec-Len).⁵
    • Tan et al (2023)⁵ presented the incidence of infections at a median follow-up of 10.8 months. Any grade infections were reported in 80.6% of patients, with grade 3/4 infections reported in 45.2% of patients.
  • Cohort E included 32 patients with RRMM who received TECVAYLI in combination with DARZALEX FASPRO and lenalidomide (Tec-DR).⁶
    • Searle et al (2022)⁶ presented the incidence of infections at a median follow-up of 8.4 months. Any grade infections were reported in 90.6% of patients, with grade 3/4 infections reported in 37.5% of patients.
• MajesTEC-4 is an open-label, randomized, multicenter, phase 3 study assessing the safety and efficacy of Tec-Len and TECVAYLI alone vs lenalidomide alone as maintenance therapy after an autologous stem cell transplant (ASCT) in patients with newly diagnosed multiple myeloma (NDMM).^14,23 
  • Zamagni et al (2024)²³ presented the incidence of infections from a safety run-in (SRI) consisting of 3 cohorts.
    • Cohort 1 (Tec-Len; TECVAYLI weekly [QW] to once every 4 weeks [Q4W]; N=32): At a median follow-up of 21.1 months, any-grade infections were reported in 93.8% of patients, with grade 3/4 infections reported in 37.5% of patients.
    • Cohort 2 (Tec-Len; TECVAYLI Q4W; N=32): At a median follow-up of 9.2 months, any-grade infections were reported in 78.1% of patients, with grade 3/4 infections reported in 28.1% of patients.
    • Cohort 3 (TECVAYLI Q4W; N=30): At a median follow-up of 9.2 months, any-grade infections were reported in 76.7% of patients, with grade 3/4 infections reported in 20.0% of patients.
• MajesTEC-5 is an open-label, nonrandomized, phase 2 study assessing the safety and efficacy of TECVAYLI- and TALVEY^® (talquetamab-tgvs)-based combination regimens in patients with transplant-eligible newly diagnosed multiple myeloma (TE-NDMM).^12,13
  • Raab et al (2024)¹³ presented the incidence of infections from 3 induction cohorts of the MajesTEC-5 study.
    • Arm A (Tec [QW]-DR; n=10): Any-grade infections were reported in 100% of patients, with grade 3/4 infections reported in 40% of patients.
    • Arm A1 (Tec [Q4W]-DR; n=20): Any-grade infections were reported in 90% of patients, with grade 3/4 infections reported in 45% of patients.
    • Arm B (TECVAYLI Q4W in combination with DARZALEX FASPRO, bortezomib, and lenalidomide; Tec [Q4W]-DVR; n=19): Any-grade infections were reported in 57.9% of patients, with grade 3/4 infections reported in 21.1% of patients.
• MajesTEC-7 is a randomized, phase 3, open-label, multicenter study comparing the safety and efficacy of Tec-DR and TALVEY in combination with DARZALEX FASPRO and lenalidomide (Tal-DR) vs DARZALEX FASPRO in combination with lenalidomide and dexamethasone (DRd) in patients with NDMM who are ineligible or not intended for transplant as initial therapy.^9,24
  • Touzeau et al (2024)²⁴ presented the incidence of infections from SRI Cohort 1 (Tec-DR) at a median follow-up of 13.8 months. Any-grade infections were reported in 100% of patients, with grade 3/4 infections reported in 30.8% of patients.
• RedirecTT-1 is an ongoing, open-label, phase 1b/2 study evaluating the safety and efficacy of TALVEY AND TECVAYLI combination in patients with RRMM.^7,15,25
  • Cohen et al (2025)^15,26 published the incidence of infections from the phase 1 dose-escalation segment of the RedirecTT-1 study.
    • All dose levels (dose levels 1-5; N=94): At a median follow-up of 20.3 months, any-grade infections were reported in 89% of patients, with grade 3/4 infections reported in 64% of patients.
• TRIMM-2 is an ongoing, phase 1b, multicohort study evaluating the safety and efficacy of DARZALEX FASPRO regimens in combination with bispecific T-cell redirecting antibodies in patients with RRMM.^8,11,27
  • D’Souza et al (2024)¹¹ presented the incidence of infections in the TECVAYLI + DARZALEX FASPRO + pomalidomide cohort at a median follow-up of 38.3 months. Any-grade infections were reported in 90% of patients, with grade 3/4 infections reported in 60% of patients.
  • Rodriguez-Otero et al (2022)⁸ presented the incidence of infections in the TECVAYLI and DARZALEX FASPRO cohort at a median follow-up of 8.6 months. Any-grade infections were reported in 67.7% of patients, with grade 3/4 infections reported in 27.7% of patients.
• Other relevant data has been identified in addition to the data summarized above:
  • Siegel et al (2024)²⁸ described a case of a female patient with MM treated sequentially with TECVAYLI and TALVEY who developed renal failure from BK virus (BKV) nephritis and fatal neurologic decline from progressive multifocal leukoencephalopathy (PML).

PRODUCT LABELING

• TECVAYLI (teclistamab-cqyv) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/TECVAYLI-pi.pdf.
• DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/DARZALEX+Faspro-pi.pdf.
• TALVEY (talquetamab-tgvs) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/TALVEY-pi.pdf.

clinical data - majestec-1 study

MajesTEC-1 (NCT03145181; NCT04557098) is evaluating the safety and efficacy of TECVAYLI in patients with RRMM.^1-3,10,17

Study Design/Methods

The main objectives 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 safety and efficacy of TECVAYLI at the RP2D.^1,29

• Key eligibility criteria:
  • Cohort A: ≥3 prior lines of therapy (LOTs) including a PI, an immunomodulatory drug, and an anti-CD38 monoclonal antibody, no prior BCMA-targeted therapy use.^1,2
  • Cohort C: ≥3 prior LOTs, including a prior PI, an immunomodulatory drug, and an anti-CD38 monoclonal antibody, enrolled patients who had prior exposure to BCMA-targeted treatment (chimeric antigen receptor [CAR]-T cell and/or antibody drug conjugate [ADC]).¹⁰
  • Prophylactic tocilizumab cohort: ≥3 prior LOTs including a PI, an immunomodulatory drug, and an anti-CD38 monoclonal antibody.³

Cohort A

van de Donk et al (2024)^18,19 conducted a post hoc analysis that evaluated the potential impact of COVID-19 on outcomes in 165 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 were managed per institutional guidelines and/or TECVAYLI interruption; vaccination (including booster doses) was recommended per availability.
• Patients with grade 5 COVID-19 infection were censored at the time of last disease evaluation for analyses of progression-free survival (PFS; n=17) and duration of response (DOR; n=13) if death was reported without disease progression. All patients who died from COVID-19 (n=18) were censored at the time of death for analysis of overall survival (OS).

Safety Results

• 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 18 patients (10.9%); 4 deaths from COVID-19 were considered by the investigators to be related to TECVAYLI treatment.
• TECVAYLI administration was interrupted in 17.6% of patients (n=29).
• 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 COVID-19, 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 were reported in 2021 (5/5 vs 5/13, respectively) compared to 2022 (0/5 vs 8/13, respectively).
• Supportive therapies were used to treat COVID-19 in 24.2% of patients, including antivirals (remdesivir) in 9.1% of patients. Additional details on management of COVID-19 infections are summarized in Table: MajesTEC-1 Study (Cohort A): Management of COVID-19 Infections.¹⁹ 

Nooka et al (2023)²⁰ published the incidence, timing, and management of infections in 165 patients receiving TECVAYLI in the MajesTEC-1 study at a median follow-up of 22.8 months (range, 0.3-33.6).

Methods

• This exploratory analysis of infections occurring in patients from MajesTEC-1 (data cutoff date January 4, 2023) included overall infections and selected categories of clinically relevant infections often observed in MM patients (including viral, COVID-19, fungal, Pneumocystis jirovecii pneumonia [PJP], respiratory and gastrointestinal [GI] infections).
• Monitoring for infections occurred frequently; infections were graded per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v4.03.
• TECVAYLI was delayed during febrile neutropenia, grade 3 neutropenia with infection, grade 4 neutropenia, or grade ≥3 nonhematologic toxicities requiring intervention or associated with an AE, and interrupted in patients with hepatitis B virus (HBV) reactivation until infection was controlled.

Safety Results

• See Table: MajesTEC-1 Study (Cohort A): Incidence and Maximum Toxicity Grade of Infections for a summary of the incidence and types of infections.
• Any-grade infections were reported in 80% of patients (n=132), with grade 3/4 infections reported in 55.2% of patients (n=91).
  • The median time to first onset of any grade infection was 1.7 months (range, 0.0-24.7) and grade ≥3 infection was 4.2 months (range, 0.0-34.6).
  • Grade 3/4 infections were more frequent within 2 months of starting TECVAYLI relative to other time points in the study.
  • Fewer grade ≥3 infections were reported between 1 and 1.5 years in patients who switched to biweekly dosing by 1 year as compared to those who remained on once weekly (QW) dosing at 1 year (15.6% vs 33.3%).
• Opportunistic infections were reported in 9.1% of patients (n=15).
• Treatment discontinuation related to infection was reported in 3% of patients (n=5) due to grade 3 adenoviral pneumonia and concurrent grade 3 PJP (n=1), grade 3 COVID-19 (n=1), grade 4 COVID-19 (n=1), grade 4 PML (n=1, from which the patient died), and grade 4 sepsis (n=1) respectively.
• A total of 21 deaths (12.7%) related to infections were reported.

Key Viral Infections (excluding COVID-19)

• Infections caused by an identified viral pathogen were reported in 12.1% of patients (n=20).
• Viral infections were most commonly caused by adenovirus (n=5; after 3-27 months), parvovirus B19 (n=5; after 11-18 months), oral herpes (n=4; after 0.6-3 months, including 3 confirmed herpes simplex virus [HSV] infections), and herpes zoster (n=3; after 5-24 months).
• Approximately half of the viral infections were reported within 6.6 months of starting TECVAYLI.
• Viral reactivations were reported as follows:
  • Adenoviral (grade 2) reactivation in 1 patient after 2.4 months.
  • Cytomegalovirus (CMV; grade 3) reactivation in 1 patient after 4.2 months.
  • CMV viremia in 2 patients after 1.2 months and 10.7 months, respectively.
  • HBV (grade 3) reactivation in 1 patient after 3.5 months (without prophylaxis).
• Treatment discontinuations were reported in 2 patients, one at 2.5 months (concurrent grade 3 adenoviral pneumonia and PJP) and the other at 13.6 months (grade 4 PML). The patient with grade 4 PML did not restart TECVAYLI treatment and died after 16.1 months.

COVID-19 Infections

• COVID-19 was reported in 29.1% of patients (n=48) overall, with grade 3/4 events reported in 21.1% of patients (n=35). Death due to COVID-19 infections was reported in 18 patients.
• COVID-19 infections (all grades) were observed throughout TECVAYLI treatment.
• Most patients were enrolled before COVID-19 vaccines were available.
• Discontinuations due to COVID-19 infections were reported in 2 patients (one due to a grade 3 COVID-19 infection at 20.7 months and another due to a grade 4 infection at 16.4 months).

Fungal Infections (excluding PJP)

• Fungal infections were reported in 5.5% of patients (n=9).
• Most fungal infections were reported approximately within the first 3 months of TECVAYLI treatment.
• A total of 4 patients had Candida infections of which 3 patients had grade 2 oral candidiasis and 1 patient had grade 2 skin Candida. These were observed after approximately 1 month of starting TECVAYLI treatment, with the exception of 1 case of oral candidiasis after 14.8 months. No fungemia was reported.
• A single grade 2 Aspergillus infection was observed in 1 patient, however the patient died from COVID-19 infection before the Aspergillus infection was resolved.

PJP Infections

• PJP infections (all grade 3/4) were reported in 7 patients (4.2%), occurring after 2.5-7.8 months of TECVAYLI treatment and lasting for 8-60 days.
• Four patients were not receiving prophylaxis at the time of infection; 2 of these 4 patients had stopped prophylaxis 3-4 months prior to the infection and 2 patients never received PJP prophylaxis.
• Treatment discontinuation was reported in 1 patient with concurrent grade 3 PJP and grade 3 adenoviral pneumonia.
• PJP resolved in all patients.

Respiratory Infections (excluding PJP and COVID-19)

• Respiratory infections were reported in 57.6% of patients (n=95), with grade 3/4 respiratory infections reported in 19.4% of patients.
• Respiratory infections (all grades) were observed throughout TECVAYLI treatment. Pneumonia was most frequently observed, most commonly due to pseudomonal pneumonia (where causative pathogen was identified).
• Deaths due to respiratory infections were reported after 1.9 months (bilateral pneumonia, pathogen unknown) and after 10.6 months (pneumococcal pneumonia).
• No treatment discontinuations were observed, however there were 30 treatment interruptions due to grade 3 infections.

GI Infections

• GI infections were reported in 9.1% of patients (n=15).
• GI infections mostly were reported within the first 13 months of TECVAYLI treatment.
• Treatment was interrupted in 2 patients with grade 3 infections, 1 patient with diverticulitis (after 2.6 months and after patient had discontinued TECVAYLI due to concurrent grade 3 PJP and grade 3 adenoviral pneumonia) and 1 patient with infectious enterocolitis (after 9.6 months).

Garfall et al (2024)¹⁷ presented the incidence of infections in Cohort A of the MajesTEC-1 study at a longer median follow-up of 30.4 months.

Safety Results

• The incidence of treatment-emergent infections at a median follow-up of 30.4 months are summarized in Table: MajesTEC-1 (Cohort A): Treatment-Emergent Infections.
• 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 have been reported since the 22.8-month follow-up.
• Treatment discontinuations due to infections were reported in 5 patients.

Cohort C Safety Results

Touzeau et al (2024)¹⁰ published the incidence of infections in Cohort C of the MajesTEC-1 study at a median follow-up of 28.0 months (range, 0.7-31.1).

• The incidence of infections is provided in Table: MajesTEC-1 Study (Cohort C): Incidence of Infections ≥10%.
• Of the 3 patients (7.5%) who discontinued TECVAYLI due to AEs, 1 case was considered treatment-related by the investigator (hepatitis E virus infection).
• One patient died due to COVID-19 that investigators considered related to TECVAYLI treatment.
• Of the 10 patients with grade 5 TEAEs:
  • One patient had a cause of death reported as cardiac arrest. This patient had pneumonia that began 10 days prior to death.
  • Four patients (10%) had a cause of death reported as COVID-19. Three patients had received at least 1 COVID-19 vaccination prior to TECVAYLI treatment, and 1 patient had no record of prior COVID-19 vaccination. Patient recruitment began in October 2020, coinciding with the COVID-19 pandemic and overlapping with peak infection and death rates globally per the World Health Organization data.

Prophylactic Tocilizumab Cohort Safety Results

van de Donk et al (2024)²¹ presented the incidence of infections in the prophylactic tocilizumab cohort of the MajesTEC-1 study at a median follow-up of 8.1 months (range, 0.9-13.2).

• Among the 24 patients who received prophylactic tocilizumab, any grade infections were reported in 79.2% of patients (n=19), with grade 3/4 infections reported in 25% of patients (n=6).
  • Infections reported were pneumonia (n=4), bacterial infection (n=1), diverticulitis (n=1), CMV infection (n=1), sepsis (n=1), and septic shock (n=1).

clinical data - Majestec-2 Study

MajesTEC-2 (NCT04722146) is an ongoing, phase 1b, multicohort, open-label study evaluating the safety and efficacy of TECVAYLI in combination with other anticancer treatments in patients with MM.^4-6,11,22

Study Design/Methods

• Key Eligibility Criteria
  • Cohort A (TECVAYLI and DARZALEX FASPRO and pomalidomide): 1 to 3 prior LOTs, including a PI and lenalidomide.¹¹
  • Cohort C (TECVAYLI and nirogacestat): disease progression within 12 months of last LOT; ≥3 prior LOTs or double refractory to a PI, and an immunomodulatory drug and triple-class exposed to a PI, an immunomodulatory drug, and an anti-CD38 monoclonal antibody. Patients with prior exposure to BCMA-targeted therapy were permitted.^4,22
  • Cohort D (Tec-Len): ≥2 prior LOTs including a PI, an immunomodulatory drug, and an anti-CD38 monoclonal antibody, no prior BCMA-targeted therapy.⁵
  • Cohort E (Tec-DR): 1 to 3 prior LOTs including a PI, and an immunomodulatory drug, no prior BCMA-targeted therapy.⁶

Cohort A Safety Results

D’Souza et al (2024)¹¹ presented the incidence of infections in Cohort A of the MajesTEC-2 study at a median follow-up of 16.2 months (range, 0.5-34.5).

• The incidence and types of infections are presented in Table: MajesTEC-2 Study (Cohort A): Infections (≥15% Overall).
• One patient died due to pseudomonal bacteremia, and 3 patients died due to COVID-19-related pneumonia.
• No fatal infections were reported following implementation of intensified infection prophylaxis, including emphasis on immunoglobulin (Ig) replacement.

Cohort C Safety Results

Offner et al (2023)⁴ presented the incidence of infections in Cohort C of the MajesTEC-2 study at a median follow-up of 14.7 months (range, 0.5-22.9).

• The incidence of infections is presented in Table: MajesTEC-2 (Cohort C): Incidence of Infections (≥20% Overall).
• No dose-limiting toxicities (DLTs) related to infections were reported.
• Infection-related deaths were reported in 4 patients (COVID-19, sepsis, septic shock and PJP).
• A single patient discontinued TECVAYLI therapy due to pneumonia.

Cohort D Safety Results

Tan et al (2023)⁵ presented the incidence of infections in Cohort D of the MajesTEC-2 study at a median follow-up of 10.8 months (range, 1.1-16.8).

• Infections of any grade were reported in 80.6% of patients (n=25), with grade 3/4 infections reported in 45.2% of patients (n=14). The most frequently reported infections were pneumonia (22.6% [all grade 3/4]), COVID-19 (any grade: 19.4%; grade 3/4: 3.2%), and sepsis (any grade: 16.1%; grade 3/4: 9.7%).

Cohort E Safety Results

Searle et al (2022)⁶ presented the incidence of infections in Cohort E of the MajesTEC-2 study at a median follow-up of 8.4 months (range, 1.1-12.9).

• The incidence and types of infections are presented in Table: MajesTEC-2 (Cohort E): Incidence of Infections.
• Additionally, grade 3/4 AEs for anorectal infection (n=1), gastroenteritis (n=1), Haemophilus infection (n=1), and urinary tract infection (n=1) have been reported.
• Two patients discontinued treatment due to an infection-related AE: COVID-19.
• Two deaths were reported due to infection-related AEs: COVID-19 (n=1, 77 days after last dose) and multi-organ failure related to sepsis (n=1).

CLINICAL DATA - MajesTEC-4 study

MajesTEC-4 (NCT05243797) is an open-label, randomized, multicenter, phase 3 study evaluating the safety and efficacy of Tec-Len and TECVAYLI alone vs lenalidomide alone as maintenance therapy in patients with NDMM.^14,23

Study Design/Methods

SRI Cohorts

• An SRI period consisting of 3 cohorts was used to establish safety prior to enrolling the randomized phase of the study.²³
• Maintenance regimen (2-year fixed duration): patients who achieved a complete response (CR) on Tec-Len after 1-year discontinued TECVAYLI and continued lenalidomide for an additional year.²³
• Key eligibility criteria: NDMM, receipt of 4 to 6 cycles of 3- or 4-drug induction therapy (PI and/or immunomodulatory drug ± anti-CD38 antibody), and ASCT (single or tandem ASCT permitted) ± consolidation with PR or better.²³

Safety Results

Zamagni et al (2024)²³ presented the incidence of infections from SRI Cohort 1 (Tec-Len; TECVAYLI QW to Q4W) at a median follow-up of 21.1 months (range, 14.8-23.8), SRI Cohort 2 (Tec-Len; TECVAYLI Q4W) at a median follow-up of 9.2 months (range, 1.2-12.2), and SRI Cohort 3 (TECVAYLI Q4W) at a median follow-up of 9.2 months (range, 3.7-11.5).

• Details on infections are provided in Table: MajesTEC-4/EMN30 Study (SRI Cohorts): Infections.
• One death due to COVID-19-related TEAE was reported in SRI Cohort 2.
• Prophylactic intravenous immunoglobulin (IVIG) replacement was advised to maintain serum IgG levels of ≥400 mg/dL. Prophylaxis for Pneumocystis carinii/Pneumocystis jirovecii pneumonia and herpes zoster reactivation and routine antibiotic and antiviral prophylaxis were recommended.

CLINICAL DATA - MajesTEC-5 study

MajesTEC-5 (GMMG-HD10; DSMM-XX) is an open-label, nonrandomized, phase 2 study assessing the safety and efficacy of TECVAYLI- and TALVEY-based combination regimens in patients with TE-NDMM.^12,13

Study Design/Methods

• Key eligibility criteria: presence of NDMM for which high-dose therapy (HDT) and ASCT were intended as part of the treatment plan, completion of HDT and ASCT within 12 months of induction start and within 6 months of the last ASCT (7 months if consolidation was received), receipt of only 1 prior LOT, and achievement of at least PR as per International Myeloma Working Group (IMWG) 2016 without evidence of progression at the time of enrollment.¹³

Safety Results

Raab et al (2024)¹³ presented the incidence of infections from 3 induction cohorts of the MajesTEC-5 study.

• Details on infections are provided in Table: MajesTEC-5 Study: Infections (>10% in Any Arm).
• No treatment discontinuations were reported due to infection.
• Infection prophylaxis, including Ig replacement, was strongly recommended. Prophylaxis for Pneumocystis jirovecii pneumonia and herpes zoster reactivation and routine antibiotic prophylaxis were recommended.

CLINICAL DATA - MajesTEC-7 study - TECVAYLI + TALVEY Cohort

MajesTEC-7 (NCT05552222) is a randomized, phase 3, open-label, multicenter study comparing the safety and efficacy of Tec-DR and Tal-DR vs DRd in patients with NDMM who are ineligible or not intended for transplant as initial therapy.^9,24

Study Design/Methods

SRI Cohort 1 (Tec-DR)

• An SRI period was used to establish safety prior to enrolling the randomized phase of the study.²⁴
• Key eligibility criteria: NDMM either ineligible or not intended for ASCT.^9,24

Safety Results

Touzeau et al (2024)²⁴ presented the initial results from the SRI of 26 patients in Cohort 1 (Tec-DR) of the MajesTEC-7 study at a median follow-up of 13.8 months (range, 2.0-15.4).

• The incidence of treatment-emergent infections is summarized in Table: MajesTEC-7 SRI Cohort 1 (Tec-DR): Treatment-Emergent Infections.
• Grade 3/4 infections did not increase with cumulative exposure to Tec-DR and most grade 3/4 infections had first onset within the first 3 treatment cycles.
• One patient discontinued all study treatment due to death in cycle 3 from influenza pneumonia.

clinical data - REDIRECTT-1 study - TALVEY + TECVAYLI COHORT

RedirecTT-1 (NCT04586426) is an ongoing, open-label, phase 1b/2 study evaluating the safety and effectiveness of the combination of TALVEY and TECVAYLI in patients with RRMM.^7,15,25

Study Design/Methods

• Key eligibility criteria: relapsed or refractory or intolerant to established therapies including the last LOT, prior exposure to a PI, an immunomodulatory drug, and an anti-CD38 monoclonal antibody.^15,25

Safety Results

Cohen et al (2025)^15,26 published the incidence of infections from the phase 1 dose-escalation segment of the RedirecTT-1 study at a median follow-up of 20.3 months (range, 0.5-37.1) in the all dose levels (dose levels 1-5) and 18.2 months in the recommended phase 2 regimen (RP2R; dose level 5) cohorts.

• Details on infections are presented in Table: RedirecTT-1 Study (TALVEY + TECVAYLI Cohort): Infections (≥5% Overall).^15,25,26
• Across all dose levels, the incidence of first onset of grade ≥3 infections was higher in the first 6 months of study treatment and then plateaued. The timing of the first onset of grade ≥3 infections is shown in Table: RedirecTT-1 Study (TALVEY + TECVAYLI Cohort): Timing of First Onset of Grade ≥3 Infections in Patients Across All Dose Levels.^15,26
• Infection prophylaxis was administered as per institutional guidelines. A total of 82% of patients (n=77) across all dose levels received antiviral prophylaxis, and 49% of the patients (n=46) received prophylaxis against Pneumocystis jirovecii pneumonia.^15,26
• In total, 63% of patients (n=59) received a COVID-19 vaccine.¹⁵
• Immunoglobulin replacement therapy (0.4 g/kg every 3-6 weeks) was recommended to maintain serum IgG levels above 400 mg/dL, regardless of current or past infections, with monitoring recommended at least every 3 months after reaching steady state.²⁶
• Immunoglobulin replacement was provided per institutional guidelines for managing serious, recurrent, or chronic infections.²⁶
• Deaths due to infections were reported in 11 patients (11.7%) in the all dose levels cohort and 3 patients (6.8%) in the RP2R cohort.^15,26

clinical data - Trimm-2 study

TRIMM-2 (NCT04108195) is an ongoing, phase 1b, 2-part, multicohort, open-label study evaluating the safety and efficacy DARZALEX FASPRO regimens in combination with bispecific T-cell redirection antibodies in patients with RRMM.^8,11,27

Study Design/Methods

• Key eligibility criteria: received ≥3 prior LOTs including a PI, immunomodulatory drug or were double refractory to PI and immunomodulatory drug; prior anti-CD38 therapy was permitted with a 90-day washout, prior BCMA-targeted therapies were also permitted.⁸

Safety Results

D'Souza et al (2024)¹¹ presented the incidence of infections in the TECVAYLI + DARZALEX FASPRO + pomalidomide cohort at a median follow-up of 38.3 months (range, 1.2-39.6).

• The incidence and types of infections are presented in Table: TRIMM-2 Study (TECVAYLI + DARZALEX FASPRO + Pomalidomide Cohort): Infections.
• Deaths due to infection were reported in 2 patients, 1 due to pneumonia and 1 due to COVID-19 pneumonia.
• No fatal infections occurred following implementation of intensified infection prophylaxis, including emphasis on Ig replacement.

Rodriguez-Otero et al (2022)⁸ presented the incidence of infections in the TECVAYLI and DARZALEX FASPRO cohort at a median follow-up of 8.6 months (range, 0.3-19.6).

• Infections were reported in 67.7% of patients (n=44); 27.7% of infections were grade 3/4.
• Three infection-related deaths were reported (bacterial pneumonia, sepsis, COVID-19). The deaths were considered unrelated to treatment with TECVAYLI or DARZALEX FASPRO.

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 21 April 2025.