SUMMARY  

• Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
• Hypogammaglobulinemia may occur in patients receiving CARVYKTI.¹
• Monitor immunoglobulin levels after treatment with CARVYKTI and administer intravenous immunoglobulin (IVIG) for immunoglobulin G (IgG) <400 mg/dL. Manage per local clinical guidelines, including antibiotic or antiviral prophylaxis and monitoring for infection.¹
• Hepatitis B Virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure and death, can occur in patients with hypogammaglobulinemia.¹
• The safety of CARVYKTI was evaluated in 396 adult patients with multiple myeloma infused with CARVYKTI in 3 open-label clinical trials; CARTITUDE-1 (MMY2001; Phase 1b/2), CARTITUDE-2 (MMY2003; Phase 2) and CARTITUDE-4 (MMY3002; Phase 3).¹
  • In pooled studies (N=396), hypogammaglobulinemia was reported in 34% of patients with 5% of patients experiencing Grade 3 hypogammaglobulinemia.¹
  • Laboratory IgG levels fell below 500 mg/dL after infusion in 91% of patients (360/396) treated with CARVYKTI.¹
  • Overall, 58% of patients received IVIG post CARVYKTI for either an adverse reaction or prophylaxis.¹
• CARTITUDE-4 (MMY3002) is a phase 3, randomized, open-label study evaluating the efficacy and safety of CARVYKTI versus standard care (physician's choice of pomalidomide, bortezomib, and dexamethasone [PVd] or DARZALEX FASPRO^® [daratumumab and hyaluronidase], pomalidomide, and dexamethasone [DPd]) in adult patients with lenalidomide-refractory MM after 1-3 prior line(s) of therapy (LOT).²
  • Adverse events (AEs) were evaluated in the safety population which included all patients who received any part of study treatment (n=208 each in the CARVYKTI and standard care arms).²
  • At a median follow-up of 15.9 months, hypogammaglobulinemia was reported in 90.9% of patients in the CARVYKTI arm and 71.6% of patients in the standard care arm based on AE reporting and laboratory results. On the basis of AE reporting alone, the corresponding incidence of hypogammaglobulinemia was 42.3% and 6.2%, respectively. IVIG was administered in 65.9% of CARVYKTI patients and 12.5% of standard care patients.²
  • At a median follow-up of 21.5 months, treatment-emergent hypogammaglobulinemia or postbaseline IgG <500 mg/dL was reported in 90.9% of CARVYKTI patients (n=189) and 71.6% of standard care patients (n=149). IVIG was administered to 68.3% of CARVYKTI patients (n=142) and 15.9% of standard care patients (n=33).³

PRODUCT LABELING

• CARVYKTI (ciltacabtagene autoleucel) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.;  https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/CARVYKTI-pi.pdf.
• DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/DARZALEX+Faspro-pi.pdf

CLINICAL DATA - CARTITUDE-4 - PHASE 3 STUDY

CARTITUDE-4 (MMY3002; clinicaltrials.gov identifier: NCT04181827) is an ongoing, phase 3, randomized, open-label study evaluating the efficacy and safety of CARVYKTI versus standard care (physician's choice of PVd or DPd) in adult patients with lenalidomide-refractory MM after 1-3 prior LOT.²

Study Design/Methods

• The study design is shown in Figure: CARTITUDE-4 Study Design.

Results

Treatment Disposition, Patient Demographics, and Disease/Treatment Characteristics

• Overall, 419 patients were randomized to receive CARVYKTI (n=208) or standard care (n=211; DPd [n=183] or PVd [n=28]).²
  • CARVYKTI as study treatment was administered to 176 patients (84.6%). Prior to receipt of CARVYKTI, 32 patients discontinued study treatment mainly due to disease progression (n=30) or death (n=2) during bridging therapy or lymphodepletion.²
    • A total of 10 patients never received CARVYKTI as study treatment; 9 of these patients died during survival follow-up.²
    • A total of 20 patients received subsequent therapy with CARVYKTI; 10 of these patients died during survival follow-up.²
  • A total of 208 patients (98.6%) were dosed with standard care. Treatment discontinuation was reported in 131 standard care patients; discontinuation due to death was reported in 5 patients.²
• High-risk cytogenetics were present in 59.4% of CARVYKTI patients and 62.9% of standard care patients. The median prior LOT in both the CARVYKTI and standard care arms were 2 (range, 1-3).^2,6

Safety - Adverse Event - Hypogammaglobulinemia  

• AEs were evaluated in the safety population, which included all patients who received any part of study treatment (n=208 each in the CARVYKTI and standard care arms).²

Median Follow-up of 15.9 Months

• At the data cut-off date of November 1, 2022, 143 patients from the CARVYKTI arm were in the post-treatment phase and 77 patients were receiving standard care.²
• At a median follow-up of 15.9 months (range, 0.1-27.3), hypogammaglobulinemia was reported in 90.9% of patients in the CARVYKTI arm and 71.6% of patients in the standard care arm based on AE reporting and laboratory results. On the basis of AE reporting alone, the corresponding incidence of hypogammaglobulinemia was 42.3% and 6.2%, respectively.²
• IVIG was administered in 65.9% of CARVYKTI patients and 12.5% of standard care patients.²

Median Follow-up of 21.5 Months

• At a median follow-up of 21.5 months (range, 0.1-32.8; data cut-off date, April 2023), treatment-emergent hypogammaglobulinemia or postbaseline IgG <500 mg/dL was reported in 90.9% of CARVYKTI patients (n=189) and 71.6% of standard care patients (n=149).³
• IVIG was administered to 68.3% of CARVYKTI patients (n=142) and 15.9% of standard care patients (n=33).³

Literature Search

A literature search of Ovid MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File databases (and/or other resources, including internal/external databases) was conducted on 13 November 2024.