Summary

• Janssen does not recommend the use of CARVYKTI in a manner that is inconsistent with the approved labeling.
• CARTITUDE-1 was a Phase 1b/2, open label, multicenter study of CARVYKTI in patients with relapse or refractory multiple myeloma (RRMM) after ≥3 prior lines of therapy (LOTs) including a proteasome inhibitor (PI), an immunomodulatory drug, and an anti-CD38 monoclonal antibody (mAb).^1-5
  • Jagannath et al (2025)^6,7 reported the overall survival (OS), ≥5-year progression-free outcomes, associated biomarkers, and safety of CARVYKTI treatment in patients with RRMM from the CARTITUDE-1 study at a median follow-up of 61.3 months.
  • Chang et al (2023)⁸ presented pharmacokinetics (PK) and pharmacodynamic (PD) profiles of CARVYKTI from 97 patients included in the CARTITUDE-1 study at a follow-up of approximately 24 months after the last patient dosed (LPD).
  • Montes de Oca et al (2023)⁹ presented the correlation of clinical response to
    CARVYKTI from the CARTITUDE-1 study at a median follow up of 33.4 months.
  • Berdeja et al (2021)¹⁰ reported the results from the CARTITUDE-1 study at a median follow-up of 12.4 months. The T_max of CAR+ T cells was 12.7 days (range, 8.754.6).
  • Wu et al (2022)¹³ developed a population-based cellular kinetic model to characterize the CAR transgene levels following a single intravenous (IV) infusion of CARVYKTI in adult patients with RRMM who were enrolled in the CARTITUDE-1 study.
• CARTITUDE-2 is a Phase 2, open-label, multicohort, single-arm, multicenter study evaluating CARVYKTI in patients with multiple myeloma (MM) in various clinical settings.¹⁴
  • Cohort A evaluates patients with RRMM who received 1-3 prior LOT and are refractory to lenalidomide.
    • Einsele et al (2022)¹⁵ presented CAR+ T expansion and persistence post-infusion, along with cytokine activity, and immune dynamics associated with CRS and neurotoxicity risk at a median follow-up of 17.1 months.
  • Cohort B evaluates patients with early relapse (≤12 months after frontline therapy or ≤12 months after autologous stem cell transplant [ASCT]).
    • van de Donk et al (2022^a)¹⁶  presented t-cell and cytokine analysis at a median follow-up of 13.4 months.
    • van de Donk et al (2022^b)¹⁷  presented CAR+ T-cell analyses at a median follow-up of 18.0 months.
  • Cohort C evaluates patients with RRMM with prior exposure to a PI, immunomodulatory drug, and an anti-CD38 mAb, and a B-cell maturation antigen (BCMA) bispecific antibody (BsAb) or antibody-drug conjugate (ADC).
    • Cohen et al (2023^a)¹⁸  presented pharmacokinetics, serum BCMA dynamics, immunogenicity, and CAR+ T-cell phenotypes at a median follow-up of 11.3 months.
    • Cohen et al (2023^b)²⁹ presented data related to CD4+ and CD8+ T cell phenotypes at a median follow-up of 18 months (range, 0.6–22.7).
  • Cohort D evaluates patients with RRMM who achieved less than a complete response (<CR) after frontline ASCT, with or without lenalidomide maintenance.
    • Arnulf et al (2024)¹⁹  presented CAR-T cell expansion profile, including patterns of CAR+ CD4 and CD8 T-cell dynamics and CD4:CD8 ratio changes following infusion at a median follow-up of 22.4 months.
  • Wu et al (2024)²² presented cellular kinetics, PD, and immunogenicity of CARVYKTI for CARTITUDE-2 Cohorts A, B, and C to study CARVYKTI in vivo expansion and its relationships with clinical factors in various MM populations.
• 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.^23,24
  • de Larrea et al (2023)²⁵ presented CAR-T cell PK and phenotypes results, sBCMA levels, and correlates of response and relapse from the CARTITUDE-4 study at a median follow-up of 16.0 months.
  • Costa et al (2024)²⁶ presented CAR+ T-cell expansion, phenotype, and baseline sBCMA levels were comparable in patients with 1 prior line of therapy, regardless of functional high-risk multiple myeloma status at a median follow-up of 15.9 months.
  • van de Donk et al (2023)²⁷ presented an analysis from CARTITUDE-4 patients comparing memory T-cell differentiation and inflammatory marker profiles in patients with and without CNP, focusing on patterns from apheresis to T_max and associated immune responses.

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; NCT03548207) was a Phase 1b/2, open label study evaluating the efficacy and safety of CARVYKTI in patients with RRMM after ≥3 prior LOT including a PI, an immunomodulatory drug, and an anti-CD38 mAb.^1-5

Study Design/Methods

• Treatment arm: CARVYKTI (single arm)
• Key eligibility criteria⁵:
  • Progressive MM per International Myeloma Working Group (IMWG) criteria
  • ≥3 prior LOTs or double refractory to a PI and an immunomodulatory drug
  • Prior exposure to a PI, an immunomodulatory drug, and an anti-CD38 mAb
  • No prior exposure to CAR-T or BCMA targeting therapy
• Primary endpoints⁵: recommended phase 2 dose (RP2D), overall response rate (ORR).

Jagannath et al (2025)^6,7 reported the overall survival (OS), ≥5-year progression-free outcomes, associated biomarkers, and safety of CARVYKTI treatment in patients with RRMM from the CARTITUDE-1 study at a median follow-up of 61.3 months.

Study Design/Methods

• Immune cell phenotypes were assessed by flow cytometry and serum biomarkers by Meso Scale Discovery (MSD).
• E:T ratio was defined as maximal CAR-positive T-cell levels (C_max) normalized by pre-infusion serum soluble BCMA (sBCMA) levels.
• sBCMA was analyzed by ligand-binding electrochemiluminescence immunoassay on day 1, prior CARVYKTI infusion.

Results

• In progression-free patients for ≥5 years vs patients with progressive disease (PD) within 5 years had the following:
  • Higher E:T ratio (P=0.008) and higher C_max ; median interquartile range (IQR; 961 cells/µL [482-1,380] vs 450 cells/µL [246-1,040]); P=0.028.
  • Higher E:T ratios for most analyzed CAR-positive T-cell subsets with higher CAR+CD4⁺central memory T-cell subsets and CAR+ T cells that were positive for activation markers CD38, CD25, and PD-1.
  • A lower neutrophil-to-leukocyte ratio (P=0.032) and higher T cell-to-neutrophil ratio (P=0.05) at the time of apheresis.
  • More CAR-positive naïve T cells in the drug product (P=0.003).
  • Higher pre-infusion hemoglobin (P=0.001), higher platelet levels (P=0.049), lower ferritin levels (P=0.158), and comparable C-reactive protein (CRP) levels (P=0.502).

Chang et al (2023)⁸ presented PK and PD profiles of CARVYKTI from the CARTITUDE-1 study. Additionally, the analysis explored the exposureresponse relationship between CARVYKTI exposure and CAR-T cell neurotoxicity, including ICANS, other neurotoxicities, and movement and neurocognitive treatment-emergent adverse events (MNTs).

Study Design/Methods

• PK was evaluated by measuring the CAR transgene copies/μg gDNA in blood using quantitative polymerase chain reaction (qPCR).
• PD was evaluated by measuring the sBCMA in serum using a ligand binding assay.
• Exposureresponse analyses were performed on the basis of the data extracted from 97 patients with approximately 24 months of follow-up after the LPD.

Pharmacokinetics

• After a single infusion, CARVYKTI showed an initial expansion phase, followed by a rapid decline, succeeded by a slower decline, demonstrating transgene persistence over the course of several months. See Figure: Mean Blood Concentration-Time Curves of CARVYKTI Transgene in CARTITUDE-1.
• CARVYKTI transgene PK are presented in Table: Transgene PK Parameters in CARTITUDE-1.
• There was no clear CARVYKTI dose-exposure (AUC_0-28d) relationship.

Pharmacodynamics

• For all 97 patients, the mean sBCMA reached nadir levels around lower limit of quantification (LLOQ) between days 78 and 100 after a single infusion.
  • Following the decline, sBCMA concentrations increased from the nadir in some patients but remained lower than baseline levels.

ExposureResponse Analyses

• There was no association between the total administered dose of CARVYKTI and the occurrence of ICANS and other neurotoxicities.
• Apparent higher median CAR-transgene PK metrics (C_max and AUC_0-28d) was observed in patients with CAR-T cell neurotoxicity vs those without neurotoxicity adverse events (AEs) for all-grade ICANS events and all-grade other neurotoxicities.
• The association between exposure and neurotoxicity AEs was not clear due to wide overlapping ranges of PK transgene levels and high interindividual variability.

Montes de Oca et al (2023)⁹ presented CARTITUDE-1 data showing the correlation between clinical response and CARVYKTI treatment in 97 patients, with a median follow-up of 33.4 months (range, 1.5-45.2).

Study Design/Methods

• Drug product, baseline, and post-infusion blood and bone marrow samples were analyzed using flow cytometry, MSD immunoassays, CITE-seq, and T-cell receptor sequencing.
• Correlations were assessed with best confirmed response and progression-free survival (PFS) at ~3-year follow-up.

Pharmacokinetics

• The drug product contained a median of 16% CAR+ T cells (range: 5–32%) and a central memory/effector memory ratio of ~1:1 (33% vs 37%).
• At T_max, CAR+CD8+ cells expanded preferentially (P=3.6×10^-24); CAR+CD4+ T cells (central memory T-cell median, 95% [range, 62-99.5]) and CAR+CD8+ T cells (central memory T-cell median, 96% [range, 33-99.7]) had a predominantly central memory phenotype. See Figure: CAR+ T-cell Characterization at T_max in CARTITUDE-1.
• CAR+ T-cell expansion and persistence were variable.
• CARVYKTI peak expansion (C_max) and persistence (T_last) were not associated with best response or PFS. See Figure: CAR-T cells C_max by Best Response in CARTITUDE-1. Longer PFS was observed in patients with a higher E:T ratio. See Figure: PFS by CAR+ T cell to sBCMA Ratio in CARTITUDE1.

Pharmacodynamics

• Baseline BCMA expression and sBCMA levels were not significantly linked to best response. However, higher baseline sBCMA was associated with shorter PFS (P=0.0098). For details see Table: Subgroup Analysis of 2-Year PFS.

Berdeja et al (2021)¹⁰ reported results from the CARTITUDE-1 study at a median follow-up of 12.4 months (interquartile range, 10.6-15.2).

Pharmacokinetics

• Overall, 113 patients enrolled/apheresed and 97 patients were treated with CARVYKTI.
• Median T_max of CAR+ T cells was 12.7 days (range, 8.7-54.6).
• Most patients who had 6 months of follow-up had CARVYKTI CAR transgene concentration below the level of quantification (<50 CAR gene copies per µg gDNA) in peripheral blood.
• Expansion and persistence of CAR+ T cells in peripheral blood at the 12.4-month followup are shown in Figure: Expansion and Persistence of CAR+ T cells in Peripheral Blood in CARTITUDE-1 (12.4-Month Follow-up).

Wu et al (2022)¹³ developed a population-based cellular kinetic model to characterize the CAR transgene levels following a single IV infusion of CARVYKTI in adult patients with RRMM who were enrolled in the CARTITUDE-1 study.

Study Design/Methods

• The CAR transgene levels in the blood were measured by qPCR.

Results

• The population analysis dataset included 1306 CARVYKTI transgene levels from all 97 patients enrolled in the CARTITUDE-1 study.
• The median of the last PK-assessment timepoints was 11.7 months (range, 1.2-23.4).

Pharmacokinetics

• After a single IV infusion, CARVYKTI exhibited an initial expansion phase followed by a rapid decline and then a slower decline with persistence over months. High
  inter-individual variability was reported.
• The number of total CAR+ viable T cells are summarized in Table: Total CAR+ Viable T cells in CARTITUDE-1.
• Model-predicted exposure metrics of CARVYKTI are described in Table: Model-Predicted PK Parameters in CARTITUDE-1.
• A covariate analysis revealed no statistically significant effect of the analyzed product-, patient-, and disease-related covariates on the PK of CARVYKTI.

CLINICAL DATA - cartitude-2 - PHASE 2 STUDY

CARTITUDE-2 (MMY2003; 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.¹⁴

Study Design/Methods

Study Design/Methods

• Treatment arm: CARVYKTI (single arm)
• Key eligibility criteria:
  • No prior CAR-T cell therapy (Cohorts A-D) or BCMA-targeted therapy (Cohorts A, B, D)
  • Cohort A: 1-3 prior LOTs, including a PI and an immunomodulatory drug; lenalidomide refractory.¹⁴
  • Cohort B: 1 prior LOT, including a PI and an immunomodulatory drug; disease progression ≤12 months after ASCT or ≤12 months from other antimyeloma therapy.¹⁴
  • Cohort C: Previously treated with a PI, an immunomodulatory drug, an anti-CD38 mAb, and BCMA BsAb or ADC.¹⁴
  • Cohort D: History of 4-8 cycles of initial therapy, including induction, high-dose chemotherapy, and ASCT with or without consolidation, in patients with <CR after frontline ASCT.^14,19,21
• Primary endpoints: Minimal residual disease (MRD) negativity at the 10^-5 sensitivity level defined by IMWG criteria (assessed by next-generation sequencing or next-generation flow).^14-18,20,30

Cohort A

Einsele et al (2022)¹⁵ presented CAR+ T expansion and persistence post-infusion, along with cytokine activity, and immune dynamics associated with CRS and neurotoxicity risk at a median follow-up of 17.1 months (range, 3.3–23.1).

• Peak expansion of CAR+ T cells occurred on day 11 (range, 8.7-42.9). The median persistence was 153 days (range, 57.1-336.8).
• The levels of IL-6, IFN-γ, IL-2Rα, and IL-10 increased after infusion and peaked at days 7-14. The levels returned to baseline within 2-3 months after infusion.
• Higher cytokine levels were associated with higher CRS severity with similar profiles for levels of IFN-γ, IL-2Rα and IL-10.
• A trend of increasing CD4/CD8 ratio being associated with increasing severities of CRS and ICANS was observed.

Cohort B

van de Donk et al (2022^a)¹⁶  presented t-cell and cytokine analysis at a median follow-up of 13.4 months (range 5.2-21.7).

• Levels of IL-6, IFN-γ, IL-2Rα, and IL-10 increased after infusion and peaked at days
  7-14. The levels returned to baseline within 2-3 months after infusion.¹⁶
• Higher IL-6 levels were associated with higher CRS severity with similar profiles for levels of IFN-γ, IL-2Rα and IL-10.¹⁶
• CD4/CD8 ratio was not associated with the severity of CRS and ICANS.¹⁶

van de Donk et al (2022^b)¹⁷  presented CAR+ T-cell analyses at a median follow-up of 18.0 months (range 5.2-26.3).

• Peak expansion of CAR+ T cells occurred on day 13 (range, 9.8-14.8). The median persistence was 76 days (range, 26.9-273.1).¹⁷
• CD4/CD8 CAR+ T-cell ratio was stable around 1:1 after CARVYKTI infusion.¹⁷

Cohort C

Cohen et al (2023^a)¹⁸  presented pharmacokinetics, serum BCMA dynamics, immunogenicity, and CAR+ T-cell phenotypes at a median follow-up of 11.3 months (range, 0.6-16.0).

• CARVYKTI PK was assessed via CAR transgene levels and CAR+ T cells in blood and bone marrow.
• Post-infusion, CAR transgene levels peaked around day 15 (range: 9-41), followed by a rapid decline and slower clearance over months. Median duration of detectable transgene: ~127 days (range: 15-213).
• CAR transgene exposure (Cmax, AUC₀–₂₈d) and CAR+ T cell levels were slightly higher in the BsAb group vs the ADC group.
• Baseline serum BCMA levels were similar between groups (ADC: 211 µg/L; BsAb: 203 µg/L) and declined post-infusion, reaching nadir near day 100.
• In all patients with progressive disease (ADC: n=7; BsAb: n=2), serum BCMA at progression resembled baseline levels. No correlation was found between baseline BCMA and response.
• ADAs were detected at baseline in 3 ADC patients (23%) but did not increase over time. No ADAs were observed in the BsAb group at any point.

Cohen et al (2023^b)²⁹ presented data related to CD4+ and CD8+ T cell phenotypes at a median follow-up of 18 months (range, 0.6–22.7)

• Central memory CAR+ T cells predominated in both CD4+ and CD8+ compartments at T_max in the prior ADC or BsAb exposure.
• At apheresis, CD4+ T cells were mainly central memory cells, while CD8+ T cells included central memory, stem cell-like memory, and TEMRA subsets.
  • T-cell phenotypes were similar in patients with prior ADC vs prior BsAb exposure.

Cohort D

Arnulf et al (2024)¹⁹  presented CAR-T cell expansion profile, including patterns of CAR+ CD4 and CD8 T-cell dynamics and CD4:CD8 ratio changes following infusion at a median follow-up of 22.4 months (range 4.7-39.3).

• CAR-T cell expansion profile is presented in Table: CARTITUDE-2 (Cohort D): CAR-T Cell Expansion Profile.¹⁹
• Both CAR+ CD4 and CAR+ CD8 T cells expanded after infusion.¹⁹
  • CAR+ CD8 T cells expanded more than CAR+ CD4 T cells in blood. See Figure: CARTITUDE-2 (Cohort D): CAR+ CD4 and CAR+ CD8 T-cell Levels.
• CAR+ CD4:CD8 T-cell ratios were lower in blood at ~T_max than in drug product (P<0.005). See Figure: CARTITUDE-2 (Cohort D): CAR+ CD4:CD8 T-cell Ratio.¹⁹

Clinical Pharmacological Characterization of CARVYKTI in CARTITUDE2

Wu et al (2024)²² presented cellular kinetics, PD, and immunogenicity data from CARTITUDE-2 Cohorts A, B, and C, evaluating CARVYKTI in vivo expansion and its relationships with clinical factors in various MM populations.

Study Design/Methods

• Cellular kinetics was evaluated in Cohorts A (first 20 patients who received CARVYKTI treated via the clinical trial process), B, and C by measuring CAR transgene copy levels and CAR⁺CD3⁺ cell levels in blood after a single infusion of 0.75 ×10⁶ CAR-positive viable T cells/kg (range, 0.5-1.0).
• For PD evaluation, sBCMA levels in serum were measured using a ligand binding assay.
• Serum samples were analyzed for antibodies binding to CARVYKTI (ie, ADAs).

Results

Pharmacokinetics

• CARVYKTI PK measurements, using transgene and cellular levels, were consistent.
• Cohorts A, B, and C showed similar cellular kinetic profiles, with an initial expansion phase followed by a rapid and then slower decline over months. High interindividual variability was noted. See Figure: Mean (+SD) Blood CARVYKTI CAR Transgene Levels vs Time Profile.
• A higher mean C_max was observed in Cohorts A and B with a lower C_max noted in Cohort C; AUC_0-28d was comparable across the 3 cohorts.
• Among Cohorts A, B, and C, median T_max ranged from 11 to 15 days, and the median time to reach below quantification levels (T_bql) was similar, ranging from 125 to 157 days. See Table: Pharmacokinetic Parameters of CARVYKTI Transgene Levels in Blood Following a Single Infusion of CARVYKTI.
• No clear dose-exposure relationship was seen across the 3 cohorts.

Pharmacodynamics

• CAR-positive T-cell expansion and persistence coincided with a reduction in sBCMA levels after a single CARVYKTI infusion.
• Mean sBCMA levels reached their nadir (LLOQ <0.250 μg/L) on day 56 for Cohort A and on day 100 for Cohorts B and C. sBCMA levels gradually increased in some patients; most patients maintained sBCMA levels significantly lower than baseline for up to 1 year after infusion.

Immunogenicity

• The overall incidence of treatment-emergent ADAs to CARVYKTI was 25.0% for Cohorts A and C and 42% for Cohort B.
• Median ADA onset ranged from 57 to 186 days across the 3 cohorts.
• Similar cellular kinetics was observed between ADA-positive and ADA-negative patients across all cohorts.
• The observed median ADA onset (57-186 days) occurred much later than the reported median T_max (approximately 14 days).
• No apparent impact of ADAs was observed on the CARVYKTI cellular kinetic parameters (C_max and AUC_0-28d).

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 (physician's choice of DPd or PVd) in adult patients with lenalidomide-refractory MM after 1-3 prior LOTs.^23,24

Additionally, the CAR-T cell PK and phenotypes results, sBCMA levels, and correlates of response and relapse from the CARTITUDE-4 study were also reported.²⁵

Study Design/Methods

• Treatment arms: Randomized 1:1 to receive either CARVYKTI or standard care (DPd or PVd)
• Key eligibility criteria²³ :
  • 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 endpoint²³: PFS

de Larrea et al (2023)²⁵ presented CAR-T cell PK and phenotypes results, sBCMA levels, and correlates of response and relapse from the CARTITUDE-4 study at a median follow-up of 16.0 months (range, 3.8-27.3).

Pharmacokinetics

• PK was evaluated in 176 treated patients; median dose: 53.1×10⁶ CAR+ viable T cells (range: 22.7-106.5×10⁶).
• CD3+ CAR+ T cells reached peak levels (C_max: 1451 cells/µL) at a median of 13 days. Additional PK parameters are shown in Table: PK Parameters in CARTITUDE-4.^23,25
• Both CAR+ CD4 and CD8 T cells expanded post-infusion, with greater expansion in CD8+ cells.
  • CD4:CD8 CAR+ ratios were lower in blood at T_max vs the drug product (P<0.0001; See Figure: CAR+ CD4 and CD8 T-cell Levels in CARTITUDE-4).
• Central memory CAR+ T cells dominated both CD4+ and CD8+ compartments at T_max.
• Peak CAR+ T-cell expansion and exposure were similar in patients with ≥CR vs ≤VGPR, though limited by response rates. For details see Figure: CAR+ T-cell Peak Expansion and Exposure in CARTITUDE-4.²⁵
• CAR+ T-cell expansion and exposure were comparable in patients with vs without progressive disease (C_max: 243 vs 510 cells/µL; AUC₀-₂₈d: 1998.5 vs 4509.9 cells×day/µL).
• sBCMA levels declined in all patients (median time to undetectability: 56 days).
  • In progressive disease, sBCMA levels rebounded post-infusion without CAR+ T-cell re-expansion.

Costa et al (2024)²⁶ reported that CAR+ T-cell expansion, phenotype, and baseline sBCMA levels were comparable in patients with 1 prior line of therapy, regardless of functional high-risk multiple myeloma status at a median follow-up of 15.9 months (range, 0.1-27.3).

Results

Pharmacokinetics

• Preferential expansion of CD8+ CAR+ T cells and dominance of central memory phenotypes were consistent across patients with and without functionally high-risk MM.
  • In patients with 1 prior LOT, with and without a functionally high-risk MM status, CAR+ CD4:CD8 T-cell ratios were notably reduced in blood at near T_max compared with the levels in the drug product. See Figure: CARTITUDE-4: CAR+ CD4:CD8 T-cell Ratios in Patients With 1 Prior LOT With and Without Functionally High-Risk MM Status.
  • Central memory CAR+ T cells were predominant in both CD4+ and CD8+ compartments at T_max across both subgroups.
• Peak CAR-T expansion and baseline sBCMA levels were similar between patients with and without functionally high-risk MM. See Figure: CARTITUDE-4: CAR-T Peak Expansion and Baseline sBCMA in Patients With 1 Prior LOT With and Without Functionally High-Risk MM Status.

van de Donk et al (2023)²⁷ presented an analysis from CARTITUDE-4 of 16/176 patients with CNP, comparing memory T-cell differentiation and inflammatory marker profiles in patients with and without CNP, focusing on patterns from apheresis to T_max and associated immune responses.

Study Design/Methods

• Peripheral blood levels of CARVYKTI and CAR+ T cells with memory phenotypes were assessed by flow cytometry.
• Serum cytokine levels were measured by multiplex sandwich immunoassays (MSD platform).

T-cell and Cytokine Analyses

• In patients with and without CNP, the differentiation pattern of memory T cells from apheresis to T_max was comparable.
  • At T_max, T cells with a central memory phenotype were dominant in the CD4 and CD8 CAR+ T compartments for patients with and without CNP.
• Patients with CNP had significantly higher CAR+ T-cell peak expansion (C_max, P=0.00049) and exposure levels (CNP onset, P=1.9×10^-5) than those without CNP (P<0.001 for both).
• Patients with vs without CNP had significantly higher C_max of IL-10 and higher exposure levels up to CNP onset of IL-10 and IL-2Rα. See Figure: Peak and AUC Levels of Serum Inflammatory Markers in CARTITUDE-4.
• Patients with CNP tended to have higher peak IL-6 and IL-2Rα levels and higher exposure levels of IL-6.
• No difference was observed between the groups in peak or exposure levels of IFN-y.

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) was conducted on 18 November 2025.