TALVEY - Use in Plasma Cell Leukemia

SUMMARY

• TALVEY is not approved by the regulatory agencies for the treatment of patients with plasma cell leukemia (PCL).
• Johnson & Johnson does not recommend the use of TALVEY in a manner that is inconsistent with the approved labeling.
• MonumenTAL-1 is an ongoing, open-label, phase 1/2 study evaluating the efficacy and safety of TALVEY in patients with relapsed or refractory multiple myeloma (RRMM).¹ 
  • Per protocol, patients with PCL (>2 x 10⁹/L plasma cells by standard differential), were excluded from enrollment.^1,2 
• Gaballa et al (2026)³ published a multicenter, retrospective study evaluating the efficacy and safety of bispecific antibodies (BsAbs), including TALVEY and TECVAYLI, in 122 patients with PCL from 15 United States (US) academic centers.
• Bernardi et al (2024)⁴ presented the clinical course of a 40-year-old male with primary plasma cell leukemia (pPCL) who was treated with TALVEY as 5^th line therapy.
• Other relevant literature has been identified in addition to the data summarized above.^5,6

PRODUCT LABELING

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

RETROSPECTIVE STUDY

Gaballa et al (2026)³ published a multicenter, retrospective Multiple Myeloma (MM) Immunotherapy Consortium study evaluating the efficacy and safety of BsAbs, including TECVAYLI and TALVEY, in patients with PCL.

Study Design/Methods

• This study included patients with primary and secondary PCL from 15 US academic centers who were treated with B-cell maturation antigen (BCMA)- or G protein-coupled receptor class C group 5 member D (GPRC5D)-directed BsAbs, including TECVAYLI, elranatamab, or TALVEY.
  • Patients received TALVEY either as definitive line of therapy (TALVEY LOT) or as bridge to chimeric antigen receptor T-cell therapy (CAR-T; TALVEY Bridge)
• PCL was defined as ≥5% circulating plasma cells (CPCs) in the peripheral blood, and included primary PCL, secondary PCL, historical PCL, and active PCL.
  • Primary PCL was defined as disease arising de novo.
  • Secondary PCL was defined as disease evolving from pre-existing MM and CPCs ≥5% for the first time at BsAb initiation, in the setting of previously diagnosed MM without prior history of PCL.
  • Active PCL was defined as active disease within 30 days of BsAb initiation.
  • Historical PCL was defined as disease that developed at any time from initial diagnosis through the last LOT prior to BsAb.
• Primary endpoints included overall response rate (ORR), progression‑free survival (PFS), and overall survival (OS).
• Secondary endpoints included incidence and severity of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), and the incidence of infections during follow-up.

Results

Treatment Disposition, Baseline Demographics, and Disease Characteristics

• A total of 122 patients with PCL who were treated with BsAbs from 15 US centers were included in this study (27% primary PCL, 73% secondary PCL, 49% active PCL, 48% historical PCL, and 3% prior PCL with unknown disease status at treatment initiation). See Table: Baseline Characteristics for additional details.

Treatment Exposure

• Patients were treated across 4 BsAb cohorts:
  • TECVAYLI: 37% (n=45)
  • TALVEY LOT: 42% (n=51)
  • TALVEY as a bridge to CAR-T: 11% (n=13)
  • Elranatamab: 11% (n=13)
• BsAbs were administered as monotherapy in 94% of patients and in combination with other agents (including pomalidomide [4%], bortezomib [1%], and chemotherapy [1%]) in 6% of patients.
• A majority of the patients receiving TALVEY were treated with the 0.8 mg/kg every-2-week regimen (96% in the TALVEY LOT cohort and 91% in the TALVEY bridge cohort), whereas only 4% and 9%, respectively, received the 0.4 mg/kg weekly schedule.

Efficacy

• Among 110 overall evaluable patients, survival outcomes varied significantly by treatment cohort at a median follow-up of 8.3 months.
  • ORR was 55%, with responses varying across treatment cohorts.
  • Summary of efficacy outcomes in overall population is shown in Table: Efficacy Outcomes by Treatment Cohort in Overall Population.

Active PCL Subgroup

• Among 60 with active PCL at the time of BsAb initiation, survival differed significantly by therapy in favor of TALVEY LOT (P<0.001 for PFS and P=0.002 for OS).
  • Median PFS was 3.2 months (95% confidence interval [CI], 0-7.9), and the median OS was 5.2 months (95% CI, 0-13).
  • Efficacy response in the evaluable patients with active PCL is shown in Table: Efficacy Outcomes by Treatment Cohort in the Evaluable Patients With Active PCL at the Time of BsAb Initiation.
  • Among patients with active PCL, PFS did not differ significantly with primary vs secondary PCL (8.8 months [95% CI, 0-18] vs 1.6 months [95% CI, 1-2.2]; P=0.15).
  • Among patients with active PCL, OS did not differ significantly with primary vs secondary PCL (12.2 months [95% CI, not calculable] vs 5.2 months [95% CI, 2.5-7.9]; P=0.054).

Historical PCL Subgroup

• Among 58 patients with historical PCL, no significant differences in survival were observed between primary (n=25) and secondary PCL (n=33).
  • Median PFS was 2.1 months (95% CI, 0-4.9) vs 5.8 months (95% CI, 2-9.6) for primary vs secondary historical PCL (P=0.2).
  • Median OS was 12.3 months (95% CI, 9.4-15.2) vs 10.4 months (95% CI, 7.2-13.6) for primary vs secondary historical PCL (P=0.85).
  • Survival outcomes in the evaluable patients with historical PCL are shown in Table: Survival Outcomes by Treatment Cohort in the Evaluable Patients With Historical PCL.
  • Among patients with historical vs active PCL, median PFS was 4.4 months (95% CI, 1.8-7) vs 1.6 months (95% CI, 0.4-2.8; P=0.036) and median OS was 10.7 months (95% CI, 5.8-15.6) vs 5.3 months (95% CI, 0-10.7; P=0.004).

Multivariable Analysis

• Active PCL was associated with worse PFS (P=0.02; hazard ratio [HR], 2.1; 95% CI, 1.1-4.02) and OS (P=0.02; HR, 2.34; 95% CI, 1.12-4.87).
• TALVEY LOT was associated with improved PFS (P=0.01; HR, 0.4; 95% CI, 0.21-0.79) and OS (P=0.01; HR, 0.4; 95% CI, 0.19-0.82).
• TALVEY bridge was associated with improved PFS (P=0.05; HR, 0.29; 95% CI, 0.08-1.01) and OS (P=0.11; HR, 0.29; 95% CI, 0.07-1.33) without reaching statistical significance for both PFS and OS.

Safety

• The median hospitalization duration was 10 days (interquartile range [IQR], 8-15).
• CRS was reported as grade 1 in 41%, grade 2 in 14.8%, grade 3 in 2.5%, and grade 4 in 1.6% of patients.
• ICANS was reported as grade 1 in 8.2%, grade 2 in 7.4%, grade 3 in 3.3%, and grade 4 in 1.6% of patients.
  • Of the patients who experienced grade 3-4 ICANS (4.9%, n=6), 3 received TECVAYLI, 2 received TALVEY, and 1 received elranatamab.
• CRS and ICANS events per PCL status are summarized in Table: CRS and ICANS According to PCL Status at BsAb Initiation.
• Infections were reported in 34% of patients, including grade 1-2 in 20% and grade ≥3 in 14% of patients.
  • Among patients with infections, viral infections were reported in 40% (n=219), bacterial infections in 36%, fungal infections in 10%, and mixed-pathogen infections in 14% of patients.
  • Infection-related deaths were reported in 4% of patients (n=5) receiving BsAbs and included pneumonia, sepsis, and bacteremia.
• No deaths were attributed to CRS or ICANS.

CASE REPORT

Bernardi et al (2024)⁴ presented the clinical course of a 40yearold male with pPCL who was treated with TALVEY as 5^th-line therapy.

• Upon diagnosis of pPCL, the patient presented with bone pain with severe anemia (7.6 g/dL hemoglobin), thrombopenia at 16 g/L, white blood cells count at 15.1 g/L with 47% circulating plasma cells, hypercalcemia, elevated lactate dehydrogenase (LDH) and β2‑microglobulin, an immunoglobulin A (IgA)-lambda of 31.6 g/L, free lambda light chains of 6,730 mg/L, and 80% bone marrow plasma cell infiltration. Chromosomal karyotyping revealed a complex karyotype with 17p13.1 loss and t(14;16), and positron emission tomography-computed tomography (PET-CT) revealed increased gastric and bone marrow activity. Gastric biopsy confirmed gastric infiltration by monoclonal plasma cells.
• The patient had received 4 prior lines of therapy before initiating TALVEY as 5^th line treatment. The 4 prior lines of therapy included:
  • Four cycles of KRD (carfilzomib, lenalidomide, dexamethasone) with weekly DARZALEX FASPRO added to cycles 3 and 4.  
  • Two cycles of VP-DACE (dexamethasone, cisplatin, doxorubicin, cyclophosphamide, etoposide, bortezomib, pomalidomide).
  • Autologous hematopoietic stem-cell transplantation (HSCT) with pomalidomide maintenance, followed by one cycle of PVD (bortezomib, dexamethasone, and pomalidomide)
  • Five cycles of elranatamab.
• Fifth-line therapy with TALVEY was started using sub-cutaneous (SC) step-up dosing of 0.01 mg/kg (day 1), 0.06 mg/kg (day 3), and 0.4 mg/kg (days 5 and 7), during which the patient developed grade 1 CRS requiring intravenous (IV) tocilizumab 8 mg/kg.
• After 2 cycles of TALVEY, the patient experienced explosive relapse characterized by a rapid increase in free light chain (FLC) and PET-CT evidence of radiologic relapse with multiple new hypermetabolic bone lesions, followed by death 3 weeks later.

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 July 2026.