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CARVYKTI®

(ciltacabtagene autoleucel)

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CARVYKTI® (ciltacabtagene autoleucel)

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CARVYKTI - CARTITUDE-2 (MMY2003) Cohort D - Use in Patients With <CR After Frontline ASCT

Last Updated: 10/01/2025

Summary

  • Janssen does not recommend the use of CARVYKTI in a manner that is inconsistent with the approved labeling.
  • CARTITUDE-2 (MMY2003) is a phase 2, multicohort, open-label study evaluating CARVYKTI in patients with multiple myeloma (MM) in various clinical settings. Cohort D is evaluating the efficacy and safety of CARVYKTI in patients who achieved less than complete response (CR) after frontline autologous stem cell transplantation (ASCT).1-4
    • Cohen et al (2025)3 presented the updated efficacy and safety results from cohort D of the CARTITUDE-2 study at a median follow-up of 40.2 months. The overall response rate (ORR) was 94.1%. At 36 months, the progression-free survival (PFS) rate and overall survival (OS) rate were 93.8% (95% confidence interval [CI], 63.2-99.1) each. The overall minimal residual disease (MRD)-negativity rate was 81.3% (95% CI, 54.4–96.0). No new safety signals were observed during this longer follow-up.
    • Arnulf et al (2024)4 presented the initial efficacy and safety results from cohort D of the CARTITUDE-2 study at a median follow-up of 22.4 months. The ORR was 94.1%. At 18 months, the PFS rate and OS rate were 93.8% (63.2-99.1) each. No grade 3/4 cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were reported. No cases on movement and neurocognitive treatment-emergent adverse event (MNT)/parkinsonism were reported.

CLINICAL DATA

CARTITUDE-2 (MMY2003; NCT04133636) is a phase 2, multicohort, open-label study evaluating CARVYKTI in patients with MM in various clinical settings.1,2

Cohort D of the CARTITUDE-2 study is evaluating the efficacy and safety of CARVYKTI with or without lenalidomide maintenance in patients who achieved <CR after frontline ASCT.3,4

Study Design/Methods

CARTITUDE-2 (Cohort D) Study Design1,2,4

Abbreviations: AE, adverse event; ASCT, autologous stem cell transplantation; ASTCT, American Society for Transplantation and Cellular Therapy; BCMA, B-cell maturation antigen; CAR, chimeric antigen receptor; cilta-cel, ciltacabtagene autoleucel; CR, complete response; CRS, cytokine release syndrome; Cy, cyclophosphamide; ECOG PS, Eastern Cooperative Oncology Group performance status; Flu, fludarabine; HDT, high-dose therapy; ICANS, immune effector cell-associated neurotoxicity syndrome; IMWG, International Myeloma Working Group; MRD, minimal residual disease; NCI-CTCAE, National Cancer Institute–Common Terminology Criteria for Adverse Events; NGF, next-generation flow-cytometry; NGS, next-generation sequencing; ORR, overall response rate; OS, overall survival; PFS, progression-free survival.
aBridging therapy was allowed when clinically indicated; alternative bridging regimens instead of, or in addition to lenalidomide were allowed.
bPer protocol, safety was assessed in the first 5 patients with cilta-cel only; subsequently, 12 patients initiated continuous lenalidomide maintenance a minimum of 21 days post cilta-cel for ≤2 years. Dose of 10 mg daily upon adequate hematologic recovery.
cAssessed per NCI-CTCAE v5.0.
dGraded per ASTCT criteria.

Cohen et al (2025)3 presented the updated efficacy and safety results from cohort D of the CARTITUDE-2 study at a median follow-up of 40.2 months (range, 4.7-55.9).

Results

Baseline Characteristics

Posttransplant Baseline Characteristics3
Characteristic
N=17
Age, median (range), years
54.0 (37-69)
Male, n (%)
14 (82.4)
Race, n (%)
   White
14 (82.4)
   Black
1 (5.9)
   Not reported
2 (11.8)
ECOG PS at screening, n (%)
   0
13 (76.5)
   1
4 (23.5)
Time from initial diagnosis to enrollment, median (range), years
0.9 (0.6-1.4)
Myeloma type by immunofixation, n (%)
   IgG
11 (64.7)
   IgA
2 (11.8)
   Light chain, kappa
2 (11.8)
   Negative immunofixation
2 (11.8)
Extramedullary plasmacytomas, n (%)
0
High-risk cytogeneticsa,b, n (%)
3 (17.6)
   del(17p)
1 (5.9)
   t(4;14)
2 (11.8)
ISS stage I, n (%)
17 (100)
Prior ASCTc, n (%)
17 (100)
Prior PI and immunomodulatory drug, n (%)
17 (100)
Prior anti-CD38 mAb, n (%)
3 (17.6)
Abbreviations: ASCT, autologous stem cell transplantation; CD, cluster of differentiation; ECOG PS,; Eastern Cooperative Oncology Group performance status; FISH, fluorescence in situ hybridization; Ig, immunoglobulin; ISS, International Staging System; mAb, monoclonal antibody; PI, proteasome inhibitor.
aCytogenetic risk abnormalities are based on central FISH testing or local FISH testing and karyotype testing if central FISH is not available. Cytogenetic risk was assessed at the time of enrollment, after induction and high-dose melphalan;high risk defined as having any of del(17p), t(4;14), t(14;16), t(14;20), or gain/amp(1q).
bTwo patients were unknown.
cOne patient received tandem ASCT (ie, underwent ASCT twice). After ASCT, 9 patients had very good partial response (VGPR) and 7 had partial response (PR); 1 patient who had tandem ASCT had VGPR after the first transplant, and status was not available after the second.
Lenalidomide Maintenance
  • Among the 17 patients included, 12 were initiated on continuous lenalidomide (10 mg daily) maintenance after treatment with CARVYKTI upon adequate hematologic recovery.3Details are presented in Table: Lenalidomide Maintenance.
  • Lenalidomide maintenance continued until confirmed progression, unacceptable toxicity, or 2 years after CARVYKTI infusion, whichever occurred first.

Lenalidomide Maintenance3
n=12
Time to initiation, median (range), days
51.0 (21.0-214.0)
Duration, median (range), days
696.5 (70.0-980.0)
Cycles, median (range)
24.5 (3.0-34.0)
Overall relative dose intensitya, median (range), %
93.4 (47.5-100)
aRelative dose intensity is calculated as the percentage of the total dose (mg) received in all relevant cycles divided by the sum of the prescribed doses (mg) in those cycles.
Efficacy
  • At a median follow-up of 40.2 months, ORR was 94.1%; all treatment responses were a stringent complete response.
  • Durable response was observed with CARVYKTI treatment.
    • At the last follow-up (range, 13.4-55.9 months), 14 of 16 responders were alive and achieved a complete response or better (≥CR).
    • At 11 months, 1 patient experienced progression and died due to multiple myeloma.
    • At 42 months, 1 patient died in a motor vehicle accident still responding to treatment.
    • At day 407, 1 patient was lost to follow-up.
  • At 36 months, the PFS and OS rates were 93.8% (95% CI, 63.2-99.1) each.
  • Thirteen of 16 MRD-evaluable patients achieved an overall MRD-negativity (at 10-5 threshold) rate of 81.3% (95% CI, 54.4-96.0).
    • MRD-negative ≥CR rates achieved by patients are presented in Table: MRD-Negativity.
    • The median time to MRD-negativity was 1.7 months (range, 0.9-11.5).
    • Patients who achieved MRD-negative ≥CR tended to have a lower level of preinfusion soluble B-cell chimeric antigen (sBCMA), a higher effector-to-target (E:T) ratio, a higher level of CD4+ naïve T cells, and a lower level of effector memory T cells at apheresis. See Figure: Baseline sBCMA.

MRD-Negativity3
n/Na
MRD-Negative ≥CR Rateb, (%)
12 months
10/14
71.4
24 months
8/11
72.7
36 months
6/8
75.0
Abbreviations: CR, complete response; IMWG, International Myeloma Working Group; MRD, minimal residual disease.
aDefined as having a positive, negative, or indeterminate MRD test at the time point (±3 months).
bDefined as the proportion of patients who were MRD-negative by bone marrow aspirate at each time point (±3 months) and achieved ≥CR based on a computerized algorithm according to IMWG response criteria at each time point (+3 months).

Baseline sBCMA3

Abbreviations: CR, complete response; sBCMA, soluble B-cell chimeric antigen; CD, cluster of differentiation; E:T, effector-to-target ratio; MRD, minimal residual disease; TN; naive T cell; TEM, effector memory T cells.
aDefined as cilta-cel peak expansion over preinfusion sBCMA.
bConsistent findings in CD8+ TN.
cConsistent findings in CD8+ TEM.

Safety
  • No new safety signals were observed during the longer follow-up.
  • CAR-T cell-related neurological events (all previously reported)4 were observed in 6 patients; most events were transient and of grade 1/2.
    • Grade 3 diplopia (recovered before previous data cutoff)4 was observed in 1 patient.
    • One patient reported grade 1 paresthesia, which was ongoing from day 18 to the time of withdrawal from the study at 4.7 months after infusion.
  • No cases of parkinsonism or Guillain-Barre syndrome were reported.
  • No new second primary malignancies (SPMs) were observed during the longer follow-up.
    • Grade 3 myelodysplastic syndrome was (previously reported; ongoing at current data cutoff) in 1 patient, with an onset on day 353; however, it was not related to CARVYKTI per investigator assessment.

Arnulf et al (2024)4 presented the initial efficacy and safety results from cohort D of the CARTITUDE-2 study at a median follow-up of 22.4 months (range, 4.7-39.3).

Results

Patient Demographics and Disease/Treatment Characteristics

CARTITUDE-2 (Cohort D): Demographics and Disease Characteristics4
Characteristic
Cohort D
N=17
Median age (range), years
54.0 (37-69)
Male, n (%)
14 (82.4)
Race, n (%)
   White
14 (82.4)
   Black/African American
1 (5.9)
   Not reported
2 (11.8)
ECOG PS at screening, n (%)
   0
13 (76.5)
   1
4 (23.5)
Time from initial diagnosis to enrollment, median (range), years
0.9 (0.6-1.4)
Myeloma type by immunofixation, n (%)
   IgG
11 (64.7)
   IgA
2 (11.8)
   Light chain, kappa
2 (11.8)
   Negative immunofixation
2 (11.8)
Extramedullary plasmacytomas, n (%)
0
High-risk cytogeneticsa, n (%)
1 (5.9)
   del17p
1 (5.9)
ISS stage l, n (%)
17 (100)
Prior ASCTb, n (%)
17 (100)
Prior PI and immunomodulatory drug, n (%)
17 (100)
Prior anti-CD38 mAb, n (%)
3 (17.6)
Abbreviations: ASCT, autologous stem cell transplant; CD, cluster of differentiation; ECOG PS, Eastern Cooperative Oncology Group performance status; FISH, fluorescence in situ hybridization; Ig, immunoglobulin; ISS, International Staging System; mAb, monoclonal antibody; PI, proteasome inhibitor.
aCytogenetic risk abnormalities are based on central FISH testing, or local FISH testing and karyotype testing if central FISH not available; 1 patient was unknown.
bOne patient received tandem ASCT, ie, underwent ASCT twice.

CARTITUDE-2 (Cohort D): Summary of Lenalidomide Maintenance After CARVYKTI 4
Characteristic
n=12
Median time to lenalidomide initiation, days (range)
51.0 (21-214)
Median lenalidomide duration, days (range)
426.5 (70-716)
Median number of lenalidomide cycles (range)
15.0 (3-26)
Median overall lenalidomide relative dose intensitya, % (range)
93.4 (68-100)
aRelative dose intensity is calculated as the percentage of total dose (mg) received in all relevant cycles divided by the sum of prescribed doses (mg) in those cycles.
Efficacy
  • Efficacy outcomes after a median follow-up of 22.4 months (range, 4.7-39.3) are presented in Table: CARTITUDE-2 (Cohort D): Efficacy - Response.4
    • One patient was lost to follow-up, and 1 patient was not evaluable for disease response.4

CARTITUDE-2 (Cohort D): Efficacy - Response4
Parameter
Cohort D
N=17
ORRa, n (%)
16 (94.1)
   sCR, %
88.2
   CR, %
5.9
≥CR, %
94.1
MRD negativity (10-5), n/N (%)
   Overall
12/17 (70.6)
   MRD-evaluable patientsb
12/15 (80.0)
Time to response among responders, median (range), months
   First response
1.3 (0.9-12.5)
   Best response
1.9 (0.9-12.5)
   ≥CR
1.7 (0.9-12.5)
Treatment response among respondersc
   Median DOR, 95% CI, months
NR (NE-NE)
   18-month DOR rate, % (95% CI)
93.3 (61.3-99.0)
18-month PFS rated,e, % (95% CI)
93.8 (63.2-99.1)
18-month OS rated,f, % (95% CI)
93.8 (63.2-99.1)
Abbreviations: ≥CR, complete response or better; CI, confidence interval; CR, complete response; DOR, duration of response; IMWG, International Myeloma Working Group; MRD, minimal residual disease; NE, not evaluable; NGF, next-generation flow; NGS, next-generation sequencing; NR, not reached; ORR, overall response rate; OS, overall survival; PFS, progression free survival; PR, partial response; sCR, stringent complete response.
aORR is defined as the proportion of patients who achieve a PR or better per IMWG criteria. Assessed using a validated computerized algorithm.
bMRD evaluable denotes patients who had successful baseline calibration for NGS or who were assessed by NGF and had at least 1 postbaseline MRD sample with positive or negative result at the threshold of 10-5.
c16 responders out of 17 patients.
dAssessed using a validated computerized algorithm.
eOne patient out of 17 patients had a PFS event.
fOne patient out of 17 patients had an OS event.
Note: Data cut-off date: September 5, 2023.
Safety
Cytokine Release Syndrome
Neurotoxicity
  • The incidence of neurotoxicity is detailed in Table: CARTITUDE-2 (Cohort D): Neurotoxicity.4
    • ICANS was reported in 1 patient, which resolved. The median time to onset of ICANS was 7 days with a median duration of 1 day.4
    • Other neurotoxicities of any grade occurred in 6 patients. A grade 3/4 event occurred in 1 patient. The median time to onset of other neurotoxicities was 21 days with a median duration of 111 days.4
      • Three patients had cranial nerve VII disorders and associated symptoms including Bell’s palsy, facial nerve palsy, facial nerve disorder, and dysarthria (grade 1 and ongoing in 1 patient, 1 patient with facial nerve palsy not resolved by data cutoff).4
      • One patient had diplopia and oral hypoesthesia, which resolved; diplopia reached a maximum of grade 3 and recovered after a duration of 43 days.4
      • One patient had grade 1 paresthesia, which was ongoing at data cutoff.4
      • One patient had peripheral motor neuropathy, dysarthria, and dysphagia, which resolved.4
    • No cases of MNTs/parkinsonism were observed.4

CARTITUDE-2 (Cohort D): Select TEAEs4
Select TEAEs, n (%)
Cohort D
(N=17)
Any Grade
Grade 3/4
Any TEAE
17 (100)
17 (100)
Serious TEAE
10 (58.8)
9 (52.9)
Infections
12 (70.6)
5 (29.4)
Hematologic
   Neutropenia
16 (94.1)
14 (82.4)
   Lymphopenia
11 (64.7)
10 (58.8)
   Thrombocytopenia
8 (47.1)
4 (23.5)
   Leukopenia
7 (41.2)
6 (35.3)
   Anemia
5 (29.4)
1 (5.9)
Abbreviation: TEAE, treatment-emergent adverse event.

CARTITUDE-2 (Cohort D): TEAEs Between Patients With or Without Lenalidomide Maintenance4
Parameter, n (%)
Cohort D
(N=17)
Cohort D Without  Lenalidomide (n=5)
Cohort D With
Lenalidomide (n=12)
Prolonged cytopeniasa
   Neutropenia
1 (5.9)
0
1 (8.3)
   Lymphopenia
5 (29.4)
2 (40.0)
3 (25.0)
   Thrombocytopenia
1 (5.9)
0
1 (8.3)
Grade 3/4 infections
5 (29.4)
1 (20.0)
4 (33.3)
Abbreviations: TEAEs, treatment-emergent adverse events.
aInitial grade 3/4 cytopenias not recovered to grade ≤2 by day 60.

CARTITUDE-2 (Cohort D): CRS4
AEs of Special Interest
Cohort D
(N=17)
Any Grade
n (%)
Grade 3/4,
n (%)
Time to Onset, Median, Days
Duration, Median, Days
CRS
14 (82.4)
0
8.0
2.5
Abbreviations: AEs, adverse events; CRS cytokine release syndrome.

CARTITUDE-2 (Cohort D): Neurotoxicity4
AEs of Special Interest
Cohort D
(N=17)
Any Grade
n (%)
Grade 3/4,
n (%)
Time to Onset, Median, Days
Duration, Median, Days
Neurotoxicity
   ICANS
1 (5.9)
0
7.0
1.0
   Other neurotoxicity
6 (35.3)
1 (5.9)
21.0
111.0
Abbreviations: AEs, adverse events; ICANS, immune effector cell-associated neurotoxicity syndrome.
Pharmacokinetics

CARTITUDE-2 (Cohort D): CAR-T Cell Expansion Profile4
(N=17)
Cmax, mean (SD), cells/μL
2129 (2113)
Tmax, median (range), days
11.74 (8.83-20.80)
Tlast, median (range), days
43 (26-210)
AUC (0-6 m), mean (SD), day×cells/μL
10,376 (7803)
Abbreviations: AUC(0-6 m), area under the CAR+ T cells concentration-time curve from time 0 to 6 months; CAR+ T cell, chimeric antigen receptor T cell; Cmax, maximum observed concentration of CAR+ T cells in blood; SD, standard deviation; Tlast, sampling time (days post infusion) of last measurable concentration of CAR+ T cells; Tmax, sampling time (days post infusion) to reach Cmax.

CARTITUDE-2 (Cohort D): CAR+ CD4 and CAR+ CD8 T-cell Levels4

A graph of a cell Description automatically generated with medium confidence

Abbreviations: CAR-T cell, chimeric antigen receptor T cell; CD cluster of differentiation.

CARTITUDE-2 (Cohort D): CAR+ CD4:CD8 T-cell Ratio4

Abbreviations: CAR-T cell, chimeric antigen receptor T cell; CD, cluster of differentiation; Cmax, maximum observed concentration of CAR+ T cells in blood; Tmax, sampling time (days post infusion) to reach Cmax.
aP value determined using the Wilcoxon test.

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 26 September 2025.

 

References

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1 Janssen Research & Development, LLC. A study of JNJ-68284528, a chimeric antigen receptor t cell (CAR-T) therapy directed against b-cell maturation antigen (BCMA) in participants with multiple myeloma (CARTITUDE-2). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2025 September 26]. Available from: https://clinicaltrials.gov/ct2/show/NCT04133636 NLM Identifier: NCT04133636.  
2 Einsele H, Van de Donk NCWJ, Arnulf B, et al. CARTITUDE-2 phase 2 multicohort study of ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen (BCMA)–directed chimeric antigen receptor T (CAR-T) cell therapy, in patients with multiple myeloma (MM). Poster presented at: 7th World Congress on Controversies in Multiple Myeloma (COMy); May 7-9, 2021; Virtual meeting.  
3 Cohen YC, Kerre T, Delforge M, et al. Efficacy/safety of cilta-cel ± lenalidomide maintenance in patients with multiple myeloma who had suboptimal response to frontline ASCT: updated follow-up from CARTITUDE-2 cohort D. Poster presented at: International Myeloma Society (IMS) Annual Meeting; September 17-20, 2025; Toronto, Canada.  
4 Arnulf B, Kerre T, Agha M, et al. Efficacy and safety of ciltacabtagene autoleucel ± lenalidomide maintenance in newly diagnosed multiple myeloma with suboptimal response to frontline autologous stem cell transplant: CARTITUDE-2 Cohort D. Oral Presentation presented at: The American Society of Clinical Oncology (ASCO) Annual Meeting; May 31–June 4, 2024; Chicago, IL.