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.
• Infections have been reported as an adverse event (AE) in the CARTITUDE-1, CARTITUDE-2 and CARTITUDE-4 studies.^1-9
• 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 anticluster of differentiation 38 (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.^1,2,5
  • In the CARTITUDE-1 study, administration of CARVYKTI may have increased the risk of infection due to cytopenias or hypogammaglobulinemia. Prolonged neutropenia may have increased the risk of infection.¹⁰
    • Please see below for a summary of permitted medications, mitigation strategies and dose delays from the CARTITUDE-1 protocol related to infections.¹⁰
  • At a median follow-up of 12.4 months, infections occurred in 58% of patients (n=56) with grade 3/4 infections observed in 20% of patients (n=19).² At a longer median follow-up of 27.7 months, treatment-emergent adverse events (TEAEs) reported were consistent with the 12.4 month median follow-up.¹ Infections were not reported at the 33.4 month follow-up. Overall, fatal infections related to CARVYKTI treatment occurred in 3 patients; lung abscess (n=1), sepsis and/or septic shock (n=2).⁵
  • In the overall population (N=97), at 61.3-month follow-up, grade ≥3 infections were reported in 9 patients.¹¹
  • The safety profile of CARVYKTI remained consistent with previously reported safety outcomes.^1,2,5,12 
    • Among the 32 patients with ≥5 years of progression-free survival (PFS), 4 new grade ≥3 infections were reported.
• CARTITUDE-2 (MMY2003) is a phase 2, multicohort, open-label study evaluating CARVYKTI in patients with multiple myeloma (MM) in various clinical settings.¹³ Janssen does not recommend the use of CARVYKTI in a manner that is inconsistent with the approved labeling.
  • Cohort A is evaluating the efficacy and safety of CARVYKTI in patients who had progressive MM after 1-3 prior lines of therapy (LOTs) and were refractory to lenalidomide.^3,7,14-16
    • Initial Subgroup: evaluated the efficacy and safety of CARVYKTI manufactured with the clinical trial process in 20 patients.^3,14-16
      • At a median follow-up of 17.1 months, 2 infection related deaths were reported due to coronavirus disease 2019 (COVID-19) (n=1; treatment related; day 100) and sepsis (n=1; not treatment related; day 394).³
    • Expansion Subgroup: evaluated the efficacy and safety of CARVYKTI manufactured with a commercial process in 23 patients.⁷
      • At a median follow-up of 15.6 months, any-grade infections occurred in 34.8% of patients (n=8), with grade 3/4 infections reported in 4.3% of patients (n=1). A treatment-related death was reported in 1 patient due to sepsis that was diagnosed on day 30.⁷
  • Cohort C is evaluating the efficacy and safety of CARVYKTI in 20 patients with RRMM after a PI, an immunomodulatory drug, an anti-CD38 antibody and a non-cellular Bcell maturation antigen (BCMA)-directed therapy. Non-cellular BCMA directed therapy included bispecific antibodies (BsAbs) and antibody-drug conjugates (ADCs).^4,17
    • At a median follow-up of 18 months, 3 infection related deaths were reported due to COVID-19 pneumonia (n=2; 1 patient in each of the ADC-exposed and BsAb-exposed groups; not treatment related) and Clostridium difficile colitis (n=1 patient in the BsAb-exposed group; treatment related).^4,17
  • Cohort D is evaluating the efficacy and safety of CARVYKTI with or without lenalidomide maintenance in 17 patients who achieved less than complete response (CR) after frontline autologous stem cell transplantation (ASCT).^8,18
    • At a median follow-up of 22.4 months, any-grade infections occurred in 70.6% of patients (n=12), with grade 3/4 infections observed in 29.4% of patients (n=5).⁸
• 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.^6,19
  • AEs were evaluated in the safety population which included all patients who received any part of study treatment (n=208 in both the CARVYKTI and standard-care arm).⁶
    • At a median follow-up of 15.9 months, infections occurred in 62.0% of patients in the CARVYKTI arm (n=129) and in 71.2% of patients in the standard-care arm (n=148).⁶ Infection related deaths were reported in 9 patients in the CARVYKTI arm (COVID-19 pneumonia: n=7; neutropenic sepsis: n=1 and pneumonia: n=1) and in 4 patients in the standard-care arm (COVID-19 pneumonia: n=1; progressive multifocal leukoencephalopathy: n=1; respiratory tract infection: n=1 and septic shock: n=1).⁹
    • At a median follow-up of 21.5 months, treatment-emergent (TE) infections of any grade were reported in 61.5% and 75.5% of patients in the CARVYKTI arm (n=128) and standard-care arm (n=157), respectively. Grade ≥3 TE infections were reported in 27.4% and 26.9% of patients in the CARVYKTI arm (n=57) and standard-care arm (n=56). Grade ≥3 events decreased substantially in the CARVYKTI arm after month 6, with a more gradual decrease over time observed in the standard‑care arm.²⁰
    • At a median follow-up of 33.6 months, infections of any grade were reported in 63.5% of patients in the CARVYKTI arm and 76.4% of patients in the standard-care arm. Grade 3/4 infections were reported in 28.4% of patients in the CARVYKTI arm and 29.8% of patients in the standard-care arm. Deaths due to TE and non-TE infections were reported in 16 patients in the CARVYKTI arm and 19 patients in the standard-care arm.¹⁹

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.^1,2,5

Study Design/Methods

• The study design is presented in the Figure: CARTITUDE-1 Study Design.

CARTITUDE-1 Study Protocol - Key Permitted Medications Related to Infections

• The following are examples of supportive therapies that may be permitted during the study:
  • Standard supportive care therapies (antibiotics and other antimicrobials and other medications intended to treat symptoms of disease) and therapies intended to treat chimeric antigen receptor (CAR) T cell related toxicity (ie, cytokine release syndrome [CRS]) as clinically indicated, according to institutional standards and as deemed necessary by the investigator.¹⁰
  • Documented infectious complications should be treated with oral or intravenous antibiotics or other anti-infective agents as considered appropriate by the treating investigator, according to standard institutional practice.¹⁰

CARTITUDE-1 Study Protocol - Potential Risks and Mitigation Strategies Related to Infections

• CARVYKTI may increase the risk of infection due to cytopenias or hypogammaglobulinemia. CARVYKTI should not be administered to patients with active infection.¹⁰
• Infection Mitigation Strategies included the following:
  • Frequent monitoring for the presence of infections, with cultures or implementation of empiric antibiotic therapy as appropriate, based on clinical judgment and institutional standards. Extended use of anti-microbial therapies for at least 6 months (or longer as per institutional guidelines) or consistent with post American Society for Transplantation and Cellular Therapy consensus guidelines after CAR
    T-cell dosing was recommended.¹⁰
  • Prolonged neutropenia may increase the risk of infections. Blood counts should be monitored after CARVYKTI infusion.¹⁰
  • Infection and CRS may have a similar presentation. Investigators are strongly encouraged to evaluate for an infection at the first signs or symptoms of CRS. Cultures and imagining should be obtained; the clinical signs and symptoms should determine which tests are appropriate.¹⁰
  • Perform screening for hepatitis B virus (HBV), hepatitis C virus, and human immunodeficiency virus and monitor as clinically indicated, and initiate treatment as appropriate. Consider cytomegalovirus serology at baseline, monitor with polymerase chain reaction testing as clinically indicated per institutional guidance.¹⁰
    • HBV reactivation, in some cases resulting in fulminant hepatitis hepatic failure and death may occur in patients treated with drugs directed against B cells such as CARVYKTI. HBV reactivation has occurred in subjects who appear to have resolved hepatitis B infection.¹⁰
  • Prophylaxis for herpes zoster reactivation is recommended during study treatment as clinically indicated and routine monitoring of HBV deoxyribonucleic acid and aspartate transaminase/alanine transaminase for patients with risk of HBV reactivation.¹⁰
• Hypogammaglobulinemia Mitigation Strategies included the following:
  • Monitor immunoglobulin (Ig) levels after treatment and treated according to local guidelines including administration of Ig replacement and monitoring for infection. Patients with IgG <400 mg/dL and recurrent infections may receive prophylactic intravenous Ig as per institutional guidelines.¹⁰

CARTITUDE-1 Study Protocol - Dose Delays Related to Infections

• Infusion of CARVYKTI infusion must be delayed for any signs of active infection. For patients requiring systemic anti-microbial treatment, or with temperature ≥38°C within 48 hours before CARVYKTI infusion, the investigator must consult with the sponsor prior to dosing.¹⁰

Results

Treatment Disposition, Patient Demographics, and Disease/Treatment Characteristics

• Overall, of the 113 patients enrolled/apheresed, 101 patients were lymphodepleted and 97 patients were treated with CARVYKTI in the combined phase 1b/2 study.¹
• Prior to lymphodepletion, a total of 12 patients discontinued (progressive disease, n=2; withdrawal by subject, n=2; deaths, n=8). Prior to CARVYKTI infusion, 3 patients withdrew from treatment, and 1 patient died.¹
• Patients received a median of 6 prior LOTs (range, 3-18), 88% of patients were triplerefractory, 42% of patients were penta-refractory, and 99% of patients were refractory to last LOT.^1,5

Safety – Adverse Event - Infections  

• At a median follow-up of 12.4 months, infections occurred in 58% of patients (n=56) with grade 3/4 infections observed in 20% of patients (n=19). Upper respiratory tract infection was reported in 16% of patients (n=15); 1 patient had a grade 3 event.²
• At a longer median follow-up of 27.7 months, TEAEs reported were consistent with the 12.4-month median follow-up. The most common grade 3/4 infections reported were pneumonia (10.3%) and sepsis (4%; n=4).^1,2
• At a median follow-up of 33.4 months (range, 1.5-45.2), infections were not reported.⁵
• Fatal infections that occurred during the study are presented in Table: CARTITUDE-1: Infection Related Deaths.
  • Fatal infections related to CARVYKTI treatment occurred in 3 patients; lung abscess (n=1), sepsis and/or septic shock (n=2).⁵

Long-Term (≥5 year) Results from the CARTITUDE-1 Study

• In the overall population (N=97), at 61.3-month follow-up, 9 patients had grade ≥3 infections.¹¹
• The safety profile of CARVYKTI remained consistent with previously reported safety outcomes.^{1,2,5,121,2,5}
  • Among the 32 patients with ≥5 years of PFS, 4 new grade ≥3 infections were reported.
• Among the 47 total deaths in CARVYKTI-treated patients overall, 17 occurred without progressive disease. Of these¹¹:
  • 4 of 7 deaths within 12 months were due to infections.
  • 3 of 6 deaths between 24–36 months were due to infections.
  • 1 of 2 deaths between 36–60 months was due to infection.

clinical data - cartitude-2 - phase 2 study

CARTITUDE-2 (MMY2003; clinicaltrials.gov identifier: NCT04133636) is an ongoing, phase 2, open-label, multicohort, single-arm, multicenter study evaluating the efficacy and safety of CARVYKTI in patients with MM in various clinical settings.¹³

• Cohort A is evaluating the efficacy and safety of CARVYKTI in patients who had progressive MM after 1-3 prior LOTs and were refractory to lenalidomide.^3,7,14-16
  • Initial Subgroup: evaluated the efficacy and safety of CARVYKTI manufactured with the clinical trial process in 20 patients.^3,14-16
  • Expansion Subgroup: evaluated the efficacy and safety of CARVYKTI manufactured with a commercial process in 23 patients.⁷
• Cohort C is evaluating the efficacy and safety of CARVYKTI in 20 patients with RRMM after a PI, an immunomodulatory drug, an anti-CD38 antibody and a non-cellular BCMAdirected therapy. Non-cellular BCMA directed therapy included BsAbs and ADCs.^4,17
• Cohort D is evaluating the efficacy and safety of CARVYKTI with or without lenalidomide maintenance in 17 patients who achieved <CR after frontline ASCT.^8,18

Study Design/Methods

• Key eligibility criteria for Cohort A: adult patients with progressive MM after 1-3 prior LOTs including a PI and an immunomodulatory drug, were lenalidomide refractory; no prior exposure to BCMA-targeting agents; Eastern Cooperative Oncology Group performance status (ECOG PS) ≤1.¹³
• Key eligibility criteria for Cohort C: adult patients previously treated with a PI, an immunomodulatory drug, an anti-CD38 antibody, and a non-cellular BCMA-directed therapy (ADC or BsAb as monotherapy or combination); diagnosis of MM per International Myeloma Working Group (IMWG) criteria, and evidence of progressive MM within 12 months of last LOT, or within 6 months of prior therapy and refractory to their most recent LOT; measurable disease at baseline; ECOG PS ≤1; BCMA expression was not required for eligibility.^4,13
• Key eligibility criteria for Cohort D: adult patients with a history of 4-8 cycles of initial therapy, including induction, high-dose therapy, and ASCT with or without consolidation; overall best response <CR; no prior exposure to BCMA-targeting agents and CAR T-cell therapy directed at any target; and ECOG PS ≤1.^8,13,18
• Key exclusion criteria related to infections: evidence of active viral or bacterial infection requiring systemic antimicrobial therapy, or uncontrolled systemic fungal infection.¹³
• Dosing: patients received a single infusion of CARVYKTI at a target dose of 0.75×10⁶ CAR+ T cells/kg (target range 0.5-1.0×10⁶) 5-7 days after the start of lymphodepletion/conditioning regimen (cyclophosphamide 300 mg/m² and fludarabine 30 mg/m² daily for 3 days on days -5 to -3).^3,4,8,13,18
• Primary endpoint: minimal residual disease (MRD) negativity at the 10^-5 sensitivity level as assessed by next-generation sequencing (clonoSEQ^®).^3,8,13,17,18
• Key Secondary endpoints: overall response rate per IMWG criteria, duration of response, time to response, time and duration of MRD negativity, and incidence and severity of AEs.^3,8,13,17,18

Results

Treatment Disposition, Patient Demographics, and Disease/Treatment Characteristics

Cohort A

• Initial Subgroup: Overall, 20 patients were enrolled, lymphodepleted and treated with CARVYKTI in Cohort A of the CARTITUDE2 study.³
  • Patients received a median of 2 prior LOTs (range, 1-3); 95% of patients were refractory to their last LOT.³
• Expansion Subgroup: Overall, 24 patients were enrolled and 23 patients were treated with CARVYKTI manufactured with a commercial process.⁷
  • Patients received a median of 3 prior LOTs (range, 1-3); 95.7% of patients were refractory to their last LOT.⁷

Cohort C

• Overall, 24 patients were enrolled/apheresed and 20 patients (7 patients in BsAb-exposed group and 13 patients in the ADC-exposed group) were treated with CARVYKTI in Cohort C of the CARTITUDE2 study.¹⁷
• Patients received a median of 8 prior LOTs (range, 4-13); 90% of patients were anti-BCMA refractory and 95% of patients were refractory to their last LOT. In total, 30% of patients (n=6) received anti-BCMA as their last line of treatment (n=4 ADC-exposed; n=2 BsAb-exposed).^4,17

Cohort D

• Overall, 17 patients were treated with CARVYKTI in Cohort D of the CARTITUDE-2 study.⁸
• In total, all 17 patients had prior ASCT and were previously exposed to PI and immunomodulatory drug; 17.6% of patients had received prior anti-CD38 monoclonal antibody therapy.⁸

Safety - Adverse Event - Infections - Cohort A

• Initial Subgroup: At a median follow-up of 17.1 months (range, 3.3-23.1), deaths related to infection were: COVID-19 (n=1; treatment related; day 100) and sepsis (n=1; not treatment related; day 394).³
• Expansion Subgroup: At a median follow-up of 15.6 months (range, 1.0-29.2), any-grade infections occurred in 34.8% of patients (n=8), with grade 3/4 infections observed in 4.3% of patients (n=1). A treatment-related death was reported in 1 patient due to sepsis that was diagnosed on day 30.⁷

Safety - Adverse Event - Infections - Cohort C

• At a median follow-up of 18 months (range, 0.6-22.7), deaths related to infection were: COVID-19 pneumonia (n=2; 1 patient in each of the ADC-exposed and the BsAb-exposed groups; not treatment related) and Clostridium difficile colitis n=1 patient in the BsAb-exposed group; treatment related).^4,17

Safety - Adverse Event - Infections - Cohort D

• At a median follow-up of 22.4 months (range, 4.7-39.3), any-grade infections occurred in 70.6% of patients (n=12), with grade 3/4 infections observed in 29.4% of patients (n=5; without lenalidomide maintenance, 20% [n=1]; with lenalidomide treatment, 33.3% [n=4]).⁸

clinical data - cartitude-4 - phase 3 study

CARTITUDE-4 (MMY3001; NCT04181827) is a Phase 3, randomized, open-label study evaluating the efficacy and safety of CARVYKTI versus standard care (physician's choice of DPd or PVd) in adult patients with lenalidomide-refractory MM after 1-3 prior LOT.^6,9

Study Design/Methods

• Treatment arms: Randomized 1:1 to receive either CARVYKTI or standard care (DPd or PVd)
• 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)

Safety - Adverse Event - Infections

• AEs were evaluated in the safety population which included all patients who received any part of study treatment (n=208 in both the CARVYKTI and standard-care arm).⁶

Median Follow-up of 15.9 Months

• At the data cut-off date of November 1, 2022, 143 patients in the CARVYKTI arm were in the post-treatment phase and 77 patients were undergoing standard-care therapy.⁹
• At a median follow-up of 15.9 months (range, 0.1-27.3), all grade infections occurred in 62.0% of patients in the CARVYKTI arm (n=129) and in 71.2% of patients in the standard-care arm (n=148) with grade 3/4 infections occurring in 26.9% of patients in the CARVYKTI arm and in 24.5% of patients in the standard-care arm.⁶
  • All grade COVID-19 infections were reported in 13.9% (n=29) in the CARVYKTI arm and 26.4% (n=55) in the standard-care arm.
    • Grade 3/4 COVID-19 occurred in 2.9% (n=6) in the CARVYKTI arm and 5.8% (n=12) in the standard-care arm.
  • All grade upper respiratory tract infections were reported in 18.8% (n=39) in the CARVYKTI arm and 26% (n=54) in the standard-care arm.
    • Grade 3/4 upper respiratory tract infections occurred in 1.9% (n=4) in the CARVYKTI arm and 1.9% (n=4) in the standard-care arm.
  • All grade lower respiratory tract/lung infections were reported in 9.1% (n=19) in the CARVYKTI arm and 17.3% (n=36) in the standard-care arm.
    • Grade 3/4 lower respiratory tract infections occurred in 4.3% (n=9) in the CARVYKTI arm and 3.8% (n=8) in the standard-care arm.
• Infection related deaths were reported in 9 patients in the CARVYKTI arm (COVID-19 pneumonia: n=7; neutropenic sepsis: n=1 and pneumonia: n=1) and in 4 patients in the standard-care arm (COVID-19 pneumonia: n=1; progressive multifocal leukoencephalopathy: n=1; respiratory tract infection: n=1 and septic shock: n=1).

Median Follow-up of 21.5 Months

• At a median follow-up of 21.5 months (range, 0.1-32.8; date cut-off date of April 2023), TE infections of any grade were reported in 61.5% of patients in the CARVYKTI arm (n=128) and 75.5% of patients in the standard-care arm (n=157). In the CARVYKTI and standard-care arms, respectively:²⁰
  • Viral infections occurred in 29.8% and 43.3% of patients.²⁰
  • Bacterial infections occurred in 16.8% and 10.6% of patients.²⁰
  • Fungal infections occurred in 5.8% and 9.6% of patients and were invasive in 4 patients (grade 3/4, n=2) and 5 patients (grade 3/4, n=2), respectively.²⁰
• Grade ≥3 TE infections were reported in 27.4% and 26.9% of patients in the CARVYKTI arm (n=57) and standard-care arm (n=56), respectively.²⁰
  • In the CARVYKTI arm, the rates were highest in the first 6 months after the study treatment start; in the standard-care arm, the rates were highest in the first 9 months. See Figure: CARTITUDE-4: Patients With Grade ≥3 TE Infections (Median Follow-up of 21.5 Months).²⁰
  • Grade ≥3 events decreased in the CARVYKTI arm after month 6; a more gradual decrease over time was observed in the standard-care arm.²⁰
• TE fatal infections occurred in 9 patients (4.3%) in the CARVYKTI arm and 6 patients (2.9%) in the standard-care arm, most of which occurred in the first 9 months after the study treatment start.²⁰
  • Overall, 7 fatal infections in the CARVYKTI arm and 2 fatal infections in the standard-care arm were due to COVID-19 pneumonia; most of these occurred during the pandemic’s omicron wave.²⁰
    • None of the patients who died of COVID-19 in the CARVYKTI arm were fully vaccinated; none of these deaths occurred after implementation of protocol-specified COVID-19 mitigation strategies.²⁰
• After infusion, among the 176 patients who received CARVYKTI as study treatment, 54 patients (30.7%) had grade ≥3 TE and non-TE infections, which occurred most often in the first 6 months after infusion.²⁰
  • Fatal TE and non-TE infections occurred in 11 patients who received CARVYKTI as study treatment, including the 7 patients in the safety set who died due to COVID-19.²⁰
• Immune recovery in patients who received CARVYKTI as study treatment:²⁰
  • B-cell counts in blood began to return to baseline levels approximately 4 months post infusion and reached baseline at approximately 9 months post infusion.²⁰
  • After treatment with CARVYKTI, IgM and IgA levels returned to baseline after approximately 1 and 2 years, respectively.²⁰
  • Starting at day 168 post infusion, the median CD4+ T cell counts began to rise above the lower limit of normal (200 x 10⁶/µL).²⁰

Median Follow-up of 33.6 Months

• At the data cut-off date of May 1, 2024, 117 patients in the CARVYKTI arm were in the post-treatment phase and 43 patients were undergoing standard-care therapy.¹⁹
• At a median follow-up of 33.6 months (range, 0.1-45.0), infections of any grade were reported in 63.5% of patients in the CARVYKTI arm and 76.4% of patients in the standard-care arm. Grade 3/4 infections were reported in 28.4% of patients in the CARVYKTI arm and 29.8% of patients in the standard-care arm. Deaths due to TE and non-TE infections were reported in 16 patients in the CARVYKTI arm and 19 patients in the standard-care arm. Complete details are provided in Table: CARTITUDE-4: Infections (Median Follow-up of 33.6 Months).¹⁹

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 27 June 2025.