SUMMARY

• Janssen does not recommend any practices, procedures, or usage that deviate from the product labeling or are not approved by the regulatory agencies.
• Stalker et al (2024)¹ published a single-center, retrospective case series evaluating patients with heavily pretreated relapsed or refractory (RR) systemic light chain (AL) amyloidosis who were treated with TECVAYLI.
• Mann et al (2023)² presented a retrospective analysis to evaluate the efficacy of TECVAYLI in 3 identified patients with RR AL amyloidosis and multiple myeloma (MM).
• Chakraborty et al (2023)³ evaluated the use of TECVAYLI in 7 patients with AL amyloidosis with or without concurrent relapsed or refractory multiple myeloma (RRMM) who were treated at 2 different medical centers.
• Forgeard et al (2023)⁴ conducted a multinational, retrospective case series analysis in patients with RR AL amyloidosis who received TECVAYLI.
• Leung et al (2023)⁵ reported the case of a 76-year-old female patient with relapsed AL amyloidosis and MM who initiated TECVAYLI after 6 prior lines of therapy (LOTs).

case series

Stalker et al (2024)¹ published a single-center, retrospective case series evaluating patients with heavily pretreated RR AL amyloidosis who were treated with TECVAYLI at the Hospital of the University of Pennsylvania.

Study Design/Methods

• Adult patients with biopsy-proven AL amyloidosis treated with TECVAYLI from December 2022 to February 2024 were included.
• The data cut-off for this analysis was February 29, 2024.
• All patients received TECVAYLI step-up dosing according to the United States prescribing information while hospitalized. All patients received monthly intravenous immunoglobulin (IVIG) and prophylaxis for pneumocystis jirovecii pneumonia (PJP) and herpes zoster.
• The revised Mayo Clinic Criteria were used to grade cardiac amyloidosis. The renal staging system was used to grade renal amyloidosis.
• Hematologic and organ response were assessed via consensus guidelines.
• Adverse events were graded based on Common Terminology Criteria for Adverse Events (CTCAE) and cytokine release syndrome (CRS) was graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) consensus scale.

Results

Baseline Characteristics

• Eight patients were included in this analysis. Baseline characteristics are presented in Table: Baseline Characteristics

Efficacy

• All patients achieved at least very good partial response (VGPR), with a median time to hematologic VGPR of 13 days (range, 12-18).
• All patients had normalization of free light chain (FLC) and 6 patients (75%) patients achieved undetectable FLC levels.
• Out of the 6 patients with completed immunofixations, all 6 achieved hematologic complete response (hCR). Median time to hCR was 88 days (range, 32-150).  
• The median difference between involved and uninvolved free light chains (dFLC) was 59.6 (range, 3.6–333.4) prior to TECVAYLI initiation and 1.4 (range, 0.0–78.5) on the first laboratory check after completion of TECVAYLI ramp-up.
• A total of 4/5 patients (80%) with cardiac involvement, achieved a cardiac response at a median time of 122 days (range, 54-292). The median N-terminal pro-B-type natriuretic peptide (NT proBNP) of the 5 patients with cardiac involvement was 1098 (range 150–35000) before TECVAYLI initiation and 337 (range 50–28120) after TECVAYLI on the most recent laboratory check by data cutoff.
• Of the 7 patients with renal involvement, 2 patients had achieved a response prior to TECVAYLI and 3 of the remaining 5 patients (60%) achieved renal response at a median time of 99 days (range, 75-347).  
• The median duration of response was 165 days (range, 11-410) from TECVAYLI start to discontinuation or censored at the last contact at the end of data collection.
• With a median duration of follow-up of 8.5 months (range, 1-14), all patients were still alive and 6 patients (75%) remained on TECVAYLI. A total of 4 patients were continued on TECVAYLI for ≥6 months; all transitioned to less frequent dosing (3 patients to every other week [Q2W] and 1 patient to every 4 weeks [Q4W]).
• With a median duration of follow-up of 13 months (range, 3-14), 5 of the 6 patients with hCR remained in hCR.

Safety

• Six patients developed CRS (grade 1, n=5; grade 2, n=1). The median time to onset of CRS was 4 days (range, 1-7). Tocilizumab was administered to 2 patients and 1 patient received steroids for CRS.
• No patients developed immune effector cell-associated neurotoxicity syndrome (ICANS).
• Two patients developed treatment-emergent neutropenia. One was Grade 3 agranulocytosis that improved with granulocyte colony-stimulating factor (G-CSF) and treatment discontinuation.
• Two cases of grade 2 acute kidney injury were reported. One case lasted 12 days and the other case initially lasted 7 days but worsened and eventually required TECVALYI discontinuation.
• Grade 3 sclerouveitis (n=1) developed 5 days after TECVAYLI initiation, and grade 3 hypertensive urgency (n=1) was reported within the first 5 days of TECVAYLI initiation.
• No patients developed cardiac decompensation while on TECVAYLI.
• Two cases of grade ≥ 3 infections requiring hospitalization were reported (grade 3 colitis [n=1] and grade 3 septic shock in the setting of a hip fracture after a fall [n=1]).
• Two patients discontinued TECVAYLI due to adverse events related to therapy.
  • A hematologic response was maintained in 1 patient 97 days after discontinuation.
  • The other patient had hematologic progression 153 days after discontinuation. Since then, this patient has resumed therapy with TECVAYLI and regained a complete response (CR).    

Mann et al (2023)² presented a retrospective analysis to evaluate the efficacy of TECVAYLI in 3 identified patients with RR systemic AL amyloidosis and MM.

Study Design/Methods

• All patients with RR AL amyloidosis and MM, who had received TECVAYLI at two US academic centers between October 2022 and July 2023 were included.
• Hematologic and organ response were assessed via consensus guidelines.
• Toxicity assessment was based on the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v5.0).
• CRS and neurotoxicity were graded according to the 2019 ASTCT criteria.
• All patients had TECVAYLI initiation in the hospital and received step-up doses of 0.06 mg/kg, 0.3 mg/kg, and 1.5 mg/kg followed by weekly outpatient doses of 1.5 mg/kg.
• CRS and neurologic toxicities were monitored according to institutional protocols.

Results

Baseline Characteristics

• A total of 3 patients (median age, 67 years [range, 54-70]; male, n=3; AL λ-type, n=2) were identified.
• The median number of prior therapies was 7 (5-10), and all the patients were refractory to bortezomib, lenalidomide and daratumumab.
• Median involved free light chain (iFLC) level was 228 mg/L (45.5-1272) with 10% median bone marrow plasmacytosis.
• One patient had rapidly progressive MM.

Efficacy

• At a median follow-up of 49 days (range, 44-58), 2 patients achieved hematologic response within 3 weeks of treatment initiation. Both responses were deep with iFLC <10 mg/L and were ongoing at the last follow-up. Summary of efficacy response has been given in Table: Summary of Efficacy Response.
• One patient with rapid renal progression prior to TECVAYLI had a renal response by day 42.

Safety

• Summary of safety and toxicity response is shown in Table: Summary of Safety and Toxicity Response.
• All patients received routine prophylaxis against Varicella zoster virus and PJP, as well as prophylactic IVIG.
• One patient with heavily pre-treated, high-risk MM had an aggressive clinical relapse with widespread osseous involvement within 6 months of an autologous stem cell transplant (ASCT) and experienced progressive disease as best response to TECVAYLI, requiring discontinuation after 29 days in favor of cytotoxic chemotherapy.

Chakraborty et al (2023)³ describes the use of TECVAYLI in 7 patients with AL amyloidosis with or without concurrent RRMM, who were treated at 2 different medical centers.

Study Design/Methods

• Patients who were treated with TECVAYLI since approval on October 25, 2022, were included.

Results

• A summary of baseline characteristics, efficacy, and safety results across the 7 patients is detailed in Table: Summary of Patients Treated With TECVAYLI for AL Amyloidosis.

Baseline Characteristics (N=7)

• Six patients had AL amyloidosis with concurrent RRMM; one patient had AL alone.
• The median dFLC was 20.5 mg/dL (range, 5.28-476.7).
• Baseline median NT proBNP was 3307 pg/mL (range, 214-19557).
• Median estimated glomerular filtration rate (eGFR) was 50 mL/min (range, 5-91), one patient was on peritoneal dialysis.
• All patients had prior exposure to anti-cluster of differentiation 38 (anti-CD38) monoclonal antibody. Four patients had prior exposure to B-cell maturation antigen (BCMA) targeted therapy. At the time of TECVAYLI initiation, 5 patients had disease refractory to the prior LOT.
• Five patients had cardiac involvement, 5 had renal involvement, and 5 had two or more organs involved.

Efficacy

• The median duration of follow-up for 6 of the 7 surviving patients was 3.2 months (range, 1.4-9.0).
• All 7 patients achieved hematologic VGPR or better.
• Median time to VGPR from TECVAYLI initiation was 0.6 months (range, 0.3-1.9).
• None of the patients had a hematologic relapse or progression at latest follow-up.

Safety

• Grade 1 CRS occurred in 4 patients. No patients developed ICANS.
• Grade 3 urinary tract infection and grade 4 septic shock secondary to gram-negative bacilli were reported in 2 patients (one each). There were no infection-related deaths.
• One patient developed cytopenia (grade 3 neutropenia and grade 3 thrombocytopenia).
• One patient died 40 days after last TECVAYLI dose due to progressive cardiac deterioration and failure to thrive.

Forgeard et al (2023)⁴ conducted a multinational, retrospective case series analysis in patients with RR AL amyloidosis who received TECVAYLI.

Study Design/Methods

• The study population included 17 patients from 10 university hospitals across Europe who were treated with TECVAYLI between July 2022 and August 2023.
• TECVAYLI was administered subcutaneously as follows: 0.06 mg/kg at day 1, 0.3 mg/kg at day 4, 1.5 mg/kg at day 8, and then 1.5 mg/kg weekly unless otherwise specified.
• Dexamethasone was administered based on local practice.
• VGPR was defined as a <40 mg/L dFLC, and partial response as dFLC decrease >50%.

Results

• Of the 17 patients, cardiac involvement was present in 16 (94%) and kidney involvement in 10 (59%).
• Additional patient characteristics at baseline are summarized in Table: Baseline Characteristics.

Efficacy

• At a median duration of follow-up of 3 months, patients had received a median of 3 cycles (range, 0.25-10) of TECVAYLI.
• Responses: A total of 15 patients (88%) achieved ≥VGPR, of whom 7 (41%) patients had achieved CR and 13 patients (76%) had a reduction of involved FLC of <10 mg/L).
  • One patient did not respond, and 1 was not evaluable due to early death.
• Median dFLC at the time of evaluation was 0 mg/L (range, 0-1370).
• The median time to best hematological response was 28 days (range, 14-112).
• Organ response: Five patients (29%) achieved an organ response (cardiac, n=4; cardiac=1; kidney, n=1), and 1 patient died of organ progression (initially Mayo IIIB).

Safety

• CRS/ICANS: A total of 9 patients (53%) had grade 1 CRS after TECVAYLI administration, and 2 patients received tocilizumab. One patient also had concomitant grade 3 ICANS (had a past history of unlabeled auto-inflammatory syndrome).
• Infections: Serious bacterial infections (grade 3-5) were reported in 5 patients (29%), of whom 1 died. Viral infections occurred in 5 patients (29%; grade 3, n=1).
• Twelve patients (71%) received IVIG during the reporting period.
• Two patients discontinued TECVAYLI due to adverse events (grade 3 ICANS and grade 5 infection).

case REPORT

Leung et al (2023)⁵ reported the case of a 76-year-old female patient with relapsed AL amyloidosis and MM who initiated TECVAYLI after 6 prior LOTs.

• Disease characteristics: At 71 years of age, she presented with positive fat aspirate for amyloid, with amyloid deposits that were not typed. Immunofixation found a monoclonal immunoglobin D (IgD) lambda, a free monoclonal lambda FLC, and an immunoglobulin G (IgG) kappa with no detectable M-spike. Serum kappa FLC was 1.95 mg/dL and lambda FLC was 825 mg/L, with a kappa to lambda ratio of 0.0024. The dFLC was 823 mg/dL. She had a subcutaneous nodule near her wrist, with a biopsy showing lambda light chain amyloid. She was diagnosed with Mayo stage IIIb by the modified European criteria and Mayo stage IV by the Mayo 2012 criteria, renal stage II AL amyloidosis.
• TECVAYLI treatment: TECVAYLI was initiated with standard step-up dosing, and the patient did not experience any CRS or neurotoxicity. She achieved stringent complete response (SCR) with a kappa FLC of 7 mg/dL, lambda FLC of 18 mg/dL, and dFLC of 11 mg/dL after 2 cycles; she remained on therapy after the completion of 6 cycles.

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 17 December 2024.