SUMMARY  

• The pharmacokinetics (PK) of CARVYKTI (CARVYKTI maximum concentration [C_max] and area under the curve in the first 28 days following CARVYKTI administration [AUC_0-28d]) was not impacted by mild hepatic dysfunction (total bilirubin ≤ upper limit of normal [ULN] and aspartate aminotransferase [AST] > ULN) or (ULN <total bilirubin ≤1.5 times ULN).¹
• Formal hepatic impairment studies of CARVYKTI were not conducted.¹
• CARTITUDE-1 (MMY2001) was a phase 1b/2, open-label, single-arm, multicenter study that evaluated CARVYKTI in patients with relapsed/refractory multiple myeloma (RRMM) who had previously received a proteasome inhibitor (PI), an immunomodulatory agent, and an anti-CD38 antibody. The combined analysis from the phase 1b/2 portions of the CARTITUDE-1 study evaluated the safety and efficacy of CARVYKTI in 97 patients with RRMM.^2-4
• 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^® [DPd]) in adult patients with lenalidomide refractory multiple myeloma (MM) after 1-3 prior lines of therapy (LOT).^5,6
  • Efficacy was evaluated in the intention-to-treat (ITT) population (all randomized patients; CARVYKTI, n=208; standard care, n=211). Subgroup analyses of progression free survival (PFS) in the CARVYKTI vs standard care arms in patients with normal and impaired baseline hepatic function (based on National Cancer Institute [NCI] criteria) favored CARYVKTI and showed effects similar to that observed in the analysis of the ITT population.^5,7
• Information pertaining to the use of CARVYKTI in patients with hepatic impairment are summarized below.

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-1 – phase 1b/2 study

CARTITUDE-1 (MMY2001; clinicaltrials.gov identifier: NCT03548207) was a phase 1b/2, open-label, single-arm, multicenter study that evaluated the safety and efficacy of CARVYKTI in patients with RRMM who had previously received a PI, an immunomodulatory agent, and an antiCD38 antibody. The combined analysis from the phase 1b/2 portions of the CARTITUDE-1 study evaluated the safety and efficacy of CARVYKTI in 97 patients with RRMM.^2-4

Study Design/Methods

CARTITUDE-1 Study Protocol - Eligibility Criteria for Hepatic Impairment  

• Select inclusion criteria included the following:
  • A total bilirubin ≤2.0 × ULN; except in patients with congenital bilirubinemia, such as Gilbert syndrome (in which case direct bilirubin ≤1.5 × ULN was required).⁸
  • AST and alanine aminotransferase (ALT) ≤3.0 × ULN.⁸
• Select exclusion criteria included the following:
  • Hepatitis B infection based on hepatitis B virus screening guide and hepatitis B virus test results. In the event the infection status is unclear, quantitative levels were necessary to determine the infection status.⁸
  • Active hepatitis C infection (anti-hepatitis C virus [HCV] antibody positive or HCV-ribonucleic acid [RNA] positive) or known to have a history of hepatitis C. For patients with known history of HCV infection, confirmation of sustained virologic response (SVR) was required for study eligibility, defined as ≥24 weeks after completion of antiviral therapy.⁸

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.^5,6

Study Design/Methods

CARTITUDE-4 Study Protocol - Eligibility Criteria for Hepatic Impairment

• Select inclusion criteria included the following:
  • A total bilirubin ≤2.0 x ULN; except in patients with congenital bilirubinemia, such as Gilbert syndrome (in which case direct bilirubin ≤1.5 x ULN was required); AST and ALT ≤3 x ULN.⁹
• Select exclusion criteria included the following:
  • Hepatitis B infection: In the event the infection status is unclear, quantitative viral levels are necessary to determine the infection status. Patients who are anti-hepatitis B serology (HBs) positive and without history of vaccination and patients with positive anti-HBc and positive anti-HBs should have hepatitis B virus (HBV)-DNA quantification test done.⁹
  • Hepatitis C infection (defined as anti-hepatitis C virus [HCV] antibody positive or HCV-ribonucleic acid [RNA] positive) or known to have a history of hepatitis C. For patients with known history of HCV infection, confirmation of sustained virologic response (SVR) was required for study eligibility, defined as ≥24 weeks after completion of antiviral therapy.⁹

Results

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]).⁵

Efficacy

ITT Population

• Efficacy was evaluated in the ITT population (all randomized patients; CARVYKTI, n=208; standard care, n=211).⁵
  • At a median follow-up of 15.9 months (range, 0.1-27.3), CARVYKTI significantly prolonged PFS vs. standard care (HR 0.26; 95% confidence interval [CI], 0.18–0.38; P<0.001); the median PFS was not reached (NR) in the CARVYKTI arm and was 11.8 months (95% CI, 9.7-13.8) in the standard care arm. The 12-month PFS rates (95% CI) for the CARVYKTI arm and standard care arms were 75.9% (69.4-81.1) and 48.6% (41.5-55.3), respectively.⁵
    • In an unweighted sensitivity analysis, CARVYKTI improved PFS compared with standard care (HR, 0.40; 95% CI, 0.29–0.55; P<0.0001).⁷
  • Subgroup analyses of PFS in the CARVYKTI vs standard care arms in patients with normal and impaired baseline hepatic function (based on NCI criteria) favored the CARYVKTI arm and showed effects similar to that observed in the analysis of the ITT population.⁷
    • Normal baseline hepatic function: HR 0.27; 95% CI (0.19-0.40).⁷
    • Impaired baseline hepatic function (mild, moderate, and severe liver dysfunction): HR 0.29; 95% CI (0.12-0.74).⁷

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 15 April 2024.