SUMMARY  

• Janssen does not recommend the use of TECVAYLI in a manner inconsistent with the approved labeling.
• Summarized in this response are select real-world studies, some of which included patients from the pre-approval access program, evaluating the overall efficacy and safety of TECVAYLI in >100 patients with relapsed or refractory multiple myeloma (RRMM).

CLINICAL DATA

Tan et al (2025)¹ conducted a retrospective, observational study involving patients ≥18 years old with RRMM treated with ≥1 dose of TECVAYLI at Memorial Sloan Kettering Cancer Center in the United States (US).

• Patients received a median of 5 prior lines of therapy (LOTs; interquartile range [IQR], 4-8). B-cell maturation antigen (BCMA)-targeted therapies were administered to 35.8% of patients (n=44), including 19.5% (n=24) who had previously received chimeric antigen receptor T (CAR-T)-cell therapy. Step-up dosing (SUD) was completed by 95.9% of patients, with 92.7% treated as inpatients, 4.1% as outpatients, and 3.3% through a hybrid approach.
• At a median follow-up of 17 months (95% confidence interval [CI], 14-20), the overall response rate (ORR) was 61.6% among 112 response-evaluable patients. Of these, 47.3% achieved a very good partial response or better (≥VGPR), including 14.3% with partial response (PR), 34.8% with very good partial response (VGPR), 11.6% with complete response (CR), and 0.9% with stringent complete response (sCR). At 18 months, 59% of patients (95% CI, 46-75) were still in response, overall survival (OS) rate was 60% (95% CI, 51-71), the progression-free survival (PFS) rate was 36% (95% CI, 27-47), and median duration of response (DOR) was not reached (NR).
• During SUD, cytokine release syndrome (CRS) was reported in 54.5% of patients (grade 1, 39%; grade 2, 13.8%; unknown, 1.6%) and immune effector cell-associated neurotoxicity syndrome (ICANS) in 13% of patients (grade 1, 4.9%; grade 2, 6.5%; grade 4, 0.8%; unknown, 0.8%). Post-SUD, no ICANS events were reported, while CRS events were reported in 1.6% of patients, all grade 1. Infections during TECVAYLI treatment were reported in 71.5% of patients, with grade 3 and 4 infections in 29.3% and 2.4%, respectively. Grade 5 infections were reported in 7.3% of patients. Among the 121 patients, ≥ 1 dose of intravenous immunoglobulin (IVIG) was administered to 6.6% of patients as primary prophylaxis against infection and to 44.6% of patients for treatment of hypogammaglobulinemia and/or infection.

Razzo et al (2025)^2,3 conducted a retrospective analysis on the efficacy and safety of TECVAYLI in 509 patients with RRMM across 15 US academic centers (US Myeloma Immunotherapy Consortium) between August 9, 2022, and January 1, 2024.

• Overall, 81% of patients (n=405) were triple-class refractory, patients received a median of 6 prior LOTs (range, 2-18), and 236 patients had previous exposure to BCMA-targeted therapy. A total of 89% of patients would have been ineligible for the MajesTEC-1 trial.
• At a median follow-up of 10.1 months (95% CI, 9.7-10.8), partial response or better (≥PR) was observed in 270 patients (53%), with 228 patients (45%) achieving ≥VGPR and 130 patients (25.3%) achieving CR/sCR. The estimated median PFS was 5.8 months (95% CI, 4.4-7.2), and the estimated 12-month OS probability was 61% (95% CI, 56-66). Among patients achieving ≥VGPR, the estimated median PFS was 16.1 months (95% CI, 13.5-NR) and the estimated 12-month OS probability was 90% (95% CI, 85-95).
• CRS was reported in 276 patients (54%); grade ≥3 CRS was reported in 7 patients (1.4%). Tocilizumab (n=163) and/or steroids (n=70) were used for the management of CRS. ICANS was reported in 57 patients (11%); grade ≥3 ICANS was reported in 11 patients (2.2%). No fatal CRS/ICANS events occurred. Infections were reported in 214 patients (42%); serious infections were reported in 113 patients (22%). Infection-related deaths were reported in 27 patients (5%). IVIG supplementation was administered to 191 patients (38%).
• In the subgroup analysis, patients with recent BCMA therapy (≤9 months) had lower responses (≥PR, 39%) compared with >9 months (56%) or no prior BCMA (58%).

Perrot et al (2025)⁴ conducted a retrospective analysis on the efficacy and safety of TECVAYLI in 303 patients with RRMM across 30 French centers from October 14, 2022, to September 14, 2023 in an early access program. The study (IFM 2024-09) was submitted to the French Health Data Hub.

• All patients were triple-class exposed, having received a median of 4 prior LOTs and 13.6% of patients (n=41) had previous exposure to BCMA-targeted therapy. TECVAYLI 1.5 mg/kg was administered subcutaneously (SC) weekly (QW) following 2 step-up doses (0.06 mg/kg and 0.3 mg/kg).
• At a median follow-up of 11.9 months (range, 9.2-14.8), the ORR was 68.8%, with 61.4% of patients achieving a ≥VGPR. The median PFS was 11.3 months (95% CI, 8.9-14.9) overall and 17 months (95% CI, 16.4-not available [NA]) in responding patients (n=175). The median OS was 17 months (95% CI, 13.8-NA).
• As of data cutoff (June 17, 2024), 125 patients (41.3%) had died, primarily from progressive disease (66.4%). No new safety signals were observed for CRS, or ICANS. Tocilizumab (n=76, 25.6%) and/or dexamethasone (n=64, 21.5%) was administered to 107 patients for CRS and/or ICANS. In 294 patients with available data, immunoglobulin (Ig) supplementation was administered in 61.4% of patients (n=186), including 41.8% (n=122) as primary prophylaxis. TECVAYLI was discontinued in 13% of patients due to infections and 29.9% of patients (n=99) were readmitted at least once for infections.  

Mohan et al (2024)⁵ conducted a retrospective cohort study on the efficacy and safety of TECVAYLI in 110 patients with RRMM across 5 US academic centers from January 2023 to August 2023.

• Overall, 86% of patients (n=95) were triple-class refractory, having received a median of 6 prior LOT and 35% of patients (n=38) had previous exposure to BCMA-targeted therapy. TECVAYLI 1.5 mg/kg was administered SC QW (or as an alternative schedule at the physician’s discretion) following 2 step-up doses (0.06 mg/kg and 0.3 mg/kg).
• At a median follow-up of 3.5 months (range, 0.4-10.9), the ORR was 62% in 98 evaluable patients, with 51% of patients achieving a ≥VGPR. ORR in patients with and without prior BCMA-targeted therapies was 54% vs 67%, respectively (P=0.23). The median PFS and median OS were NR. The estimated 6-month PFS and OS were 52% (95% CI, 42-64) and 80% (95% CI, 72-89), respectively.
• As of data cutoff (August 31, 2023), CRS was reported in 56% of patients; grade 3 CRS was reported in 1 patient and grade 4 was reported in 4 patients. ICANS was reported in 11% of patients (n=12); ≥grade 3 ICANS was reported in 5 patients (4.5%) with 1 grade 5 event. Tocilizumab was administered to 36% of patients (n=40) for CRS and systemic steroids were administered for CRS and/or ICANS in 17% of patients (n=19). Overall, 78 infections were diagnosed in 44 patients; all grades and ≥grade 3 infections were 40% (n=44) and 26% (n=29), respectively. IVIG supplementation was administered to 43% of patients (n=46) as primary prophylaxis.

Dima et al (2024)⁶ conducted a retrospective analysis on the efficacy and safety of TECVAYLI in 106 patients with RRMM, including patients in an expanded access program, across 5 US academic centers (US Myeloma Innovations Research Collaborative) from August 1, 2022, to August 15, 2023.

• Overall, 92% of patients were triple-class refractory, having received a median of 6 prior LOT and 53% of patients (n=56) had previous exposure to BCMA-targeted therapy. TECVAYLI 1.5 mg/kg was administered SC QW following 2 step-up doses (0.06 mg/kg and 0.3 mg/kg).
• At a median follow-up of 3.8 months, 45% of patients (n=46) had progressed while on TECVAYLI. The ORR was 66%, with 29% of patients achieving a ≥CR. The median PFS was 5.4 months (95% CI, 3.4-NR) and median OS was NR (95% CI, NR-NR). The estimated 10-month OS rate was 67% (95% CI, 57-79). The ORR in the BCMA exposed subgroup was 59%. Patients who initiated treatment with TECVAYLI within three months of their last BCMA-directed therapy showed lower ORR (42.9% vs 64.3%; P=0.27) and ≥VGPR (35.7% vs 47.6%; P=0.64) compared to those who started TECVAYLI more than three months after their last BCMA therapy.
• CRS was reported in 64% of patients (n=68); grade 3 CRS was reported in 1 patient and recurrent CRS was reported in 2 patients. Tocilizumab was administered to 40% of patients (n=42) and systemic steroids were administered in 21% of patients (n=22) for CRS. A total of 16 ICANS events were reported in 15 patients; grade 3 ICANS was reported in 2 patients and grade 4 was reported in 1 patient. Tocilizumab and corticosteroids were administered in 1 and 14 patients, respectively, for ICANS. A total of 39 infections were reported in 33 patients; 46% were grade 3 or 4. IVIG supplementation was administered to 42% of patients (n=44). A total of 29 patients died, primarily from progressive disease (86%).

Reidhammer et al (2024)^7,8 conducted a retrospective analysis on the efficacy and safety of TECVAYLI in 123 patients with RRMM across 18 German centers from July 2022 to October 2023. Patients received TECVAYLI through the pre-approval access program or may have received commercial TECVAYLI.

• Overall, 92.6% of patients were triple-class refractory, having received a median of 6 prior LOT and 37.4% of patients (n=45) had previous exposure to BCMA-targeted therapy. TECVAYLI 1.5 mg/kg was administered SC QW following 2 step-up doses (0.06 mg/kg and 0.3 mg/kg).
• At a median follow-up of 5.5 months, the ORR was 59.3%, with 22.0% of patients achieving a complete or near CR and 26.0% of patients achieving a VGPR. The median PFS was 8.7 months (55% events still censored at data cutoff) and median OS was NR. The median interval from last BCMA-directed therapy to TECVAYLI was 6.0 months in anti-BCMA-pretreated patients. The ORR was 54.8% in BCMA-pretreated patients, compared with 64.5% in BCMA-naïve patients. The difference was exclusively noted for patients pretreated with ide-cel (n=21) having an ORR of 33% (P< 0.01, chi-square test). The DOR was NR in patients with ≥PR and did not differ significantly between ide-cel-pretreated and ide-cel-naïve patients (P=0.54). Response rates did not significantly differ by interval from prior CAR-T to TECVAYLI initiation (>3 vs <3 months: 33% vs 20%, P=0.57; >6 vs <6 months: 22% vs 36%, P=0.49).
• CRS was reported in 58.5% of patients (n=72); grade ≥3 CRS was reported in 2 patients. ICANS was reported in 7.3% of patients (n=9); grade ≥3 ICANS was reported in 1 patient. Tocilizumab was administered to 23.6% and dexamethasone to 16.2% of patients. Infections were reported in 54.5% of patients (n=67); grade ≥3 infections were reported in 26.8% of patients (n=33).

Razzo et al (2024)⁹ conducted a retrospective analysis on the efficacy and safety of TECVAYLI in 385 patients with RRMM across 14 centers in the US Myeloma Immunotherapy Consortium from October 2022 to October 2023.

• Overall, 84% of patients were triple-class refractory, having received a median of 6 prior LOT and 58% of patients had previous exposure to gene, cellular or BCMA targeted therapies.  
• The ORR was 55%, with 12% of patients achieving a sCR and 13% of patients achieving a CR. At a median potential follow-up of 9.21 months, the median PFS was 6.64 months (95% CI, 5.69-8.94) and 17.49 months (95% CI, 13.32-NR) in patients achieving a ≥PR (n=211). The median OS was NR (95% CI, 13.38-NR).
• ORR was 62% of patients without prior BCMA exposure, compared to 49% in patients with prior exposure (P=0.01). Mean PFS was 8.94 months in BCMA-naïve patients vs 5.72 in patients with prior BCMA exposure (P=0.042). In patients achieving ≥VGPR, mean PFS was 17.5 months in the BCMA-naïve group vs NR in patients with prior BCMA exposure (P=0.433).
• Among 187 patients, prior BCMA-directed therapy included ide-cel in 40% of patients (n=75), belantamab in 26% of patients (n=48), ide-cel plus belantamab in 14% of  patients (n=26), other agents in 12% of patients (n=22), 5.3% of patients cilta-cel (n=10), belantamab plus other in 1.1% of patients (n=2), cilta-cel plus belantamab in 1.1% of patients (n=2), and ide-cel plus other in 1.1% of patients (n=2). A total of 117 of 164 evaluable patients (71%) had achieved ≥PR to prior BCMA therapy. The median time from last anti-BCMA therapy to TECVAYLI was 286 days (IQR 1,330; range 3).
• CRS was reported in 57% of patients (n=219); grade ≥3 CRS was reported in 4 patients. ICANS was reported in 12% of patients (n=48); grade ≥3 ICANS was reported in 10 patients (2.6%). Infections were reported in 43% of patients (n=166); grade ≥3 infections were reported in 22% of patients (n=83).

Tan et al (2024)¹⁰ conducted a retrospective analysis on the long-term efficacy and safety of TECVAYLI in 223 patients with RRMM across 9 academic centers in 5 countries from May 24, 2022, to January 4, 2024. Data were collected until September 30, 2024.

• A total of 83% of patients were triple-class refractory, having received a median of 6 prior LOT and 42% of patients had previous exposure to BCMA-targeted therapy.
• At a median follow-up of 16 months (95% CI, 14-17), the ORR was 66% in 207 response-evaluable patients, with 27% of patients achieving a sCR/CR and 32% of patients achieving a VGPR. The median PFS was 7.6 months (95% CI, 5.5-14) and the median OS was 20 months (95% CI, 18-NR). The ORR was 75% in BCMA-naïve patients, compared with 53% in patients with prior BCMA exposure (P=0.001).
• Infections occurred in 58.3% of patients (n=130); 25.1% of which were grade ≥3, including 10 patients with grade 5 infection. A total of 35.4% of patients (n=79) had ≥2 infections while on TECVAYLI.

Balev et al (2024)¹¹ conducted a retrospective analysis on the efficacy and safety of TECVAYLI in 168 patients with RRMM across 5 US academic centers.

• Overall, 83% of patients were triple-class refractory, having received a median of 5 prior LOT and 33% of patients had previous exposure to BCMA-targeted therapy.
• At a median follow-up of 8.5 months, the ORR was 71%, with 60% of patients achieving a ≥VGPR. The median PFS was 12 months, and median OS was 18 months.
• CRS was reported in 54% of patients (grade ≥3, 0.6%). ICANS was reported in 9.0% of patients (grade ≥3, 1.8%). Infections were reported in 54.8% of patients (grade ≥3, 30.2%). Deaths related to infections were reported in 2.3% of patients. Primary IVIG prophylaxis was administered to 38% 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 23 September 2025.