TALVEY – Use in Immunoglobulin Light Chain (AL) Amyloidosis

SUMMARY

• Johnson & Johnson does not recommend the use of TALVEY in a manner that is inconsistent with the approved labeling.
• Shragai et al (2026)¹ published a retrospective case series of 6 patients with relapsed/refractory (RR) AL amyloidosis who were treated with TALVEY in 2 centers.
• Even-Zohar et al (2025)² published a case report of the use of TALVEY in a 64-year old female patient with AL amyloidosis.

Case series/reports

Shragai et al (2026)¹ published a retrospective case series of 6 patients with RR AL amyloidosis who were treated with TALVEY in 2 centers. The median follow-up was 9.6 months (range, 1-22).

Methods

• All patients received TALVEY step-up dosing per local prescribing information.
• Patient data was obtained from medical electronic charts.
• The Revised Mayo Clinic Criteria were used for staging of cardiac amyloidosis.
• Minimal residual disease (MRD) was assessed using fluorescence activated cell sorting at a sensitivity threshold of 10⁻⁵. AEs were graded based on Common Terminology Criteria for Adverse Events (CTCAE); cytokine release syndrome (CRS) and immune cell-associated neurotoxicity syndrome (ICANS) were graded according to American Society for Transplantation and Cellular Therapy (ASTCT) consensus guidelines.

Results

Baseline Characteristics, Disease/Treatment Disposition

• The median age was 63 years (range, 53-74).
• Two patients had concurrent multiple myeloma. Systemic involvement included heart (n=5), kidneys (n=5), peripheral nervous system (n=3), soft tissue (n=3), gastrointestinal (n=2), and liver (n=1). Three patients had ≥3 organ involved at baseline.
• At treatment initiation, 2 patients had Mayo stage 3 or 4 disease.
• Abnormal cytogenetics were reported in 5 patients, including 1q gain (n=2), del13 (n=2), del17p (n=1), t(4;14) (n=1), and t (11;14) (n=1).
• The median prior lines of therapy (LOT) were 7 (range, 2-11). Patients were universally refractory to daratumumab, bortezomib, cyclophosphamide, and pomalidomide. Four patients were refractory to lenalidomide and belantamab mafodotin, and one patient with t(11;14) was refractory to venetoclax. Three patients received anti-BCMA CAR-T cell therapy.
• TALVEY was initiated for progressive disease (n=4) and inadequate response (n=2) for a median of 71 months (range, 8-132) and administered for a median of 5.2 cycles (range, 1-22).

Efficacy

• Five patients (83%) achieved a hematologic response, all of whom reached complete response (CR).
• The median time to documented hematological response was 26 days (range, 21-63).
• At data cutoff, 3 patients were alive and were in CR after 24, 15 and 9 months from the first dose of TALVEY; none of these patients required subsequent therapy.
• Of the 3 patients assessed for MRD-negativity, all tested negative; two of whom had sustained MRD-negativity at 6 months and 9 months.

Safety

• CRS occurred in 4 patients, all of which were grades 1-2.
• ICANS occurred in 2 patients (grade 3, n=1; grade 5, n=1).
• Severe infections occurred in 2 patients (grade 3, n=1; grade 5, n=1). Transient exacerbation of congestive heart failure occurred in 2 patients (grade 3, n=1; grade 4, n=1).
• Patients also reported dysgeusia (grade 2, n=2), xerostomia (grade 2, n=2), weight loss (grade 2, n=2), anemia (grade 3, n=1), fever/thrombocytopenia (grade 2, n=1).
• Three patients died during TALVEY treatment (sepsis, n=1; cardiac failure, n=1; primary refractory, n=1). None were attributed to TALVEY treatment. Time from TALVEY initiation to death was 6 months, 6 weeks, and 4 weeks, respectively.

Even-Zohar et al (2025)² reported the case of a 64-year-old female patient with relapsed AL amyloidosis and cardiac involvement, who initiated TALVEY after 10 prior LOTs. The findings from this case report are current at the time of article submission (March 2025).

Results

Baseline Characteristics, Disease/Treatment Disposition

• The patient was diagnosed in 2004 following sudden cardiac arrest and successful resuscitation.
• Upon diagnosis, the patient presented with 10-20% kappa-restricted plasma cells on bone marrow aspirate, t(4;14) translocation on florescence in situ hybridization (FISH), serum free kappa light chain (FLC) of 1800 mg/L, and positive Congo red staining.
• The patient’s presentation was consistent with that of AL amyloidosis with involvement of the heart, kidneys, gastrointestinal tract, soft tissue, autonomic nervous system and liver.
• The patient had previously received 10 prior LOTs, including combinations of alkylators, immunomodulatory agents, proteasome inhibitors, anti-CD38 and anti-BCMA agents.
• As a result of multiple lines of therapy, TALVEY was administered on a compassionate use basis. The patient received TALVEY 0.01 mg/kg on day 1, 0.03 mg/kg on day 4, 0.4 mg/kg on day 7, and 0.8 mg/kg on day 21. Premedication regimens were administered prior to each dose escalation.

Efficacy

• The patient achieved stringent complete response with a reduction in kappa FLC from 92.5 mg/dL to 0.16 mg/dL and difference in serum FLC (dFLC) from 92 mg/dL to 0 mg/dL within 3 weeks of receiving the full TALVEY treatment dose.
• After 6 months of treatment, she was MRD-negative at a sensitivity of 10^-5 by next-generation flow cytometry. Serum and urine immunofixations were also negative.
• She continued treatment after a year and a half, with dFLC maintained between 0 and 1.

Safety

• No CRS or neurotoxicity events were reported.
• Two weeks after the first full treatment dose, the patient developed grade 2 asthenia and dizziness which resolved after dexamethasone treatment.
• Grade 2 dysgeusia and weight loss (12% of body weight) were reported but eventually stabilized and remained stable.
• Hypogammaglobulinemia was observed prior to TALVEY treatment and worsened after initiation but was managed with IVIG 0.5 g/kg every 4 weeks. After follow-up, the patient only experienced 2 episodes of grades 1-2 respiratory tract infections.
• Grade 2 thrombocytopenia (platelets, 70,000/L) and anemia (Hb, 11 g/dL) were reported; anemia eventually became grade 3 (Hb, 9 g/dL; mean corpuscular volume [MCV], 110). There was no evidence of myelodysplasia and all other hematologic laboratory markers were within normal ranges.

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 16 September 2026.