SUMMARY  

• 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, CARTITUDE-2 and CARTITUDE-4.¹ 
  • In pooled studies (N=396), hypogammaglobulinemia was reported in 34% of patients with 5% of patients experiencing Grade 3 hypogammaglobulinemia.
  • Laboratory IgG levels fell below 500 mg/dL after infusion in 91% of patients (360/396) treated with CARVYKTI.
  • Overall, 58% of patients received IVIG post CARVYKTI for either an adverse reaction or prophylaxis.
• CARTITUDE-4 is a phase 3, open-label, multicenter study evaluating CARVYKTI versus standard care regimens, DARZALEX FASPRO (daratumumab and hyaluronidase), pomalidomide, and dexamethasone (DPd) or pomalidomide, bortezomib, and dexamethasone (PVd), in patients with RRMM who received 1-3 prior LOT, including a proteasome inhibitor and an immunomodulatory drug, and are refractory to lenalidomide.²
  • van de Donk et al (2024) presented hypogammaglobinemia and immune reconstitution after a median follow of 21.5 months. Hypogammaglobulinemia (IgG <500 mg/dL postbaseline) occurred in 90.9% of CARVYKTI patients compared to 71.6% with standard care. IVIG was administered to 68.3% of CARVYKTI patients versus 15.9% with standard care.³
  • San-Miguel et al (2023) published primary results of CARTITUDE-4 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 adverse event (AE) reporting and laboratory results. IVIG was administered in 65.9% of CARVYKTI patients and 12.5% of standard care patients.²

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; NCT04181827) is a phase 3, randomized, open-label study evaluating the efficacy and safety of CARVYKTI versus standard care (PVd or DPd) in patients with lenalidomide-refractory MM after 1-3 prior LOTs.²

Study Design/Methods^2,4,5 

• Treatment arm: Randomized 1:1 to receive either CARVYKTI or standard care (PVd or DPd)
• Key eligibility criteria:
  • Received 1-3 prior lines of therapy including a PI and an immunomodulatory drug  
  • Refractory to lenalidomide
  • No prior exposure to CAR-T or BCMA targeting therapy
• Primary endpoint: Progression-free survival (PFS)

van de Donk et al (2024) presented hypogammaglobinemia and immune reconstitution after a median follow of 21.5 months (range, 0.1-32.8).³

• 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).
• IgM levels returned to baseline ~1 and 2 years, respectively, after treatment with CARVYKTI as shown in Figure: Blood Levels of IgM.
  • Measurement of IgG recovery is confounded by IVIG supplementation; however, it is expected to occur between 1 and 2 years, based on IgM recovery.

San-Miguel et al (2023) published hypogammaglobinemia and IVIG usage in CARTITUDE-4 at a median follow-up of 15.9 months (range, 0.1-27.3).²

• 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.
• 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.

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 17 November 2025.