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 evaluating the overall efficacy and safety of TECVAYLI in >100 patients with relapsed or refractory multiple myeloma (RRMM).

CLINICAL DATA

Perrot et al (2024)¹ 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 lines of therapy (LOT) and 13.6% of patients (n=41) had previous exposure to B-cell maturation antigen (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 overall response rate (ORR) was 68.8%, with 61.4% of patients achieving a very good partial response (VGPR) or better. The median progression-free survival (PFS) was 11.3 months (95% confidence interval [CI], 8.9-14.9) overall and 17 months (95% CI, 16.4-not available [NA]) in responding patients (n=175). The median overall survival (OS) was 17 months (95% CI, 13.8-NA).
• As of data cut-off (June 17, 2024), 125 patients (41.3%) had died, primarily from progressive disease (66.4%). No new safety signals were observed for cytokine release syndrome (CRS), or immune effector-cell associated neurotoxicity syndrome (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)² conducted a retrospective cohort study on the efficacy and safety of TECVAYLI in 110 patients with RRMM across 5 United States (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. The median PFS and median OS were not reached (NR). The estimated 6-month PFS and OS were 52% (95% CI, 42-64) and 80% (95% CI, 72-89), respectively.
• As of data cut-off (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. Intravenous immunoglobulin (IVIG) supplementation was administered to 43% of patients (n=46) as primary prophylaxis.

Dima et al (2024)³ 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 complete response (CR) or better. 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).
• 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)⁴ 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.

• 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 cut-off) and median OS was NR.
• 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)⁵ 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 anti-BCMA targeted therapies.  
• The ORR was 55%, with 12% of patients achieving a stringent complete response (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 partial response or better (n=211). The median OS was NR (95% CI, 13.38-NR).
• 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)⁶ 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).
• 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)⁷ 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 07 February 2025.