CARVYKTI- Adverse Event - Hypogammaglobulinemia

SUMMARY  

• Johnson & Johnson does not recommend the use of CARVYKTI in a manner that is inconsistent with the approved labeling.
• 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 (Ig) levels after treatment with CARVYKTI and administer intravenous immunoglobulin (IVIG) for 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 (MM) 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 relapsed refractory multiple myeloma who received 1-3 prior lines of therapy (LOTs), including a proteasome inhibitor (PI) and an immunomodulatory drug, and are refractory to lenalidomide.^2,3
  • Einsele et al (2026)^3,4 published treatment-emergent hypogammaglobulinemia and IVIG use in safety population at a median follow-up of 33.6 months (interquartile range [IQR], 20.3-35.0). Grade 3 hypogammaglobulinemia was reported in 7.7% of patients (n=16) in the CARVYKTI arm and 1% of patients (n=2) in the standard-care arm. IVIG was administered to 71% of CARVYKTI patients (n=147) and 20% of standard-care patients (n=42).
  • van de Donk et al (2024)⁵ presented hypogammaglobulinemia 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.
  • San-Miguel et al (2023)² 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.

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 (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.^2,3

Study Design/Methods^2,6 

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

Einsele et al (2026)³ published treatment-emergent hypogammaglobulinemia and IVIG use in safety population of the CARTITUDE-4 study at a median follow-up of 33.6 months (IQR, 20.3-35.0). 

• At the May 1, 2024 data cutoff, 117 patients in the CARVYKTI arm were in the post‑treatment phase and 43 patients were receiving standard care; the safety population included 208 patients from both treatment arms.^3,4
  • Grade 1/2 hypogammaglobulinemia was reported in 37.5% of patients (n=78) in CARVYKTI arm and 7.7% of patients (n=16) in standard-care arm.
  • Grade 3 hypogammaglobulinemia was reported in 7.7% of patients (n=16) in CARVYKTI arm and 1.0% of patients (n=2) in standard-care arm.
  • No grade 4/5 hypogammaglobulinemia events were reported in the safety population.
• IVIG was administered to 71% of CARVYKTI patients (n=147) and 20% of standard care patients (n=42).³

van de Donk et al (2024)⁵ presented hypogammaglobulinemia and immune reconstitution at a median follow of 21.5 months (range, 0.1-32.8).

• 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)² published hypogammaglobulinemia and IVIG usage in CARTITUDE-4 at a median follow-up of 15.9 months (range, 0.1-27.3).

• 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 16 March 2026.