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CARVYKTI® (ciltacabtagene autoleucel)
Medical Information

CARVYKTI - Prior Lines of Therapy in CARTITUDE-1 and CARTITUDE-4

Last Updated: 03/05/2026

Summary

  • CARTITUDE-1 is a phase 1b/2, open label, multicenter study of CARVYKTI in patients with relapsed or refractory multiple myeloma (RRMM) after ≥3 prior lines of therapy (LOTs) including a proteasome inhibitor (PI), an immunomodulatory drug, and an anti- cluster of differentiation (CD) 38 monoclonal antibody (mAb).1-3
    • Patients received a median of 6 (range, 3-18) prior LOTs; 88% of patients were triple-class refractory, 42% of patients were penta-drug refractory and 99% of patients were refractory to the last LOT.1
    • After a median follow-up of 21.7 months and 27.7 months, responses were observed in most patients in high-risk subgroups (overall response rate [ORR] range, 95.1%-100%) including patients with 3 or ≥4 prior LOTs and patients who were tripleclass or penta-drug refractory.1,4
    • After a median follow-up of 61.3 months, patients who remained progression-free for ≥5 years had a slightly higher median number of prior LOTs (6.5 vs 5.0) compared to those who experienced progression within 5 years.3
    • The incidence of cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and other chimeric antigen receptor-T (CAR-T) cell neurotoxicities (events not reported as ICANS) in the subgroups was consistent with the overall population.4
  • 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 LOTs, including a PI and an immunomodulatory drug, and are refractory to lenalidomide.5,6

PRODUCT LABELING

CLINICAL DATA - CARTITUDE-1 - PHASE 1B/2 STUDY

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

Study Design/Methods

  • Treatment arm: CARVYKTI (single arm)
  • Key eligibility criteria:
    • Progressive MM per International Myeloma Working Group 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 B-cell maturation antigen (BCMA) targeting therapy
  • Primary endpoints: Recommended phase 2 dose, ORR

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.1,2 Patient details are presented in Table: CARTITUDE-1: Select Demographics and Disease Characteristics.
  • Patients received a median of 6 prior LOTs (range 3-18); 88% of patients were tripleclass refractory, 42% of patients were penta-class refractory, and 99% of patients were refractory to the last LOT.1-3

CARTITUDE-1: Select Demographics and Disease Characteristics1-3
Characteristics
Total (N=97)
Median age, years (range)
61.0 (56-68)
Median prior LOT, n (range)
6 (3-18)
Prior LOT, n (%)
   3
17 (17.5)
   4
16 (16.5)
   ≥5
64 (66.0)
Received bridging therapy, n (%)
73 (75)
Prior stem-cell transplantation, n (%)
   Autologous
87 (90)
   Allogenic
8 (8)
Previous PIs
   Carfilzomib, n (%)
      Exposed
83 (86)
      Refractory
63 (65)
   Bortezomib, n (%)
      Exposed
92 (95)
      Refractory
66 (68)
   Ixazomib, n (%)
      Exposed
29 (30)
      Refractory
27 (28)
Previous immunomodulatory agents
   Lenalidomide, n (%)
      Exposed
96 (99)
      Refractory
79 (81)
   Pomalidomide, n (%)
      Exposed
89 (92)
      Refractory
81 (84)
Previous anti-CD38 monoclonal antibody
   Daratumumab, n (%)
      Exposed
94 (97)
      Refractory
94 (97)a
Triple-class exposedb, n (%)
97 (100)
   Triple-class refractory, n (%)
85 (88)
Penta-drug exposedc,n (%)
81 (84)
   Penta-drug refractory, n (%)
41 (42)
Refractory to last LOT, n (%)
96 (99)
Abbreviations: CD38, cluster of differentiation 38; LOT, line of therapy; PI, proteasome inhibitor.
aAdditionally, 2 more patients were refractory to other anti-CD38 antibodies.
bAt least 1 PI, 1 immunomodulatory agent, and 1 anti-CD38 antibody.
c≥2 PIs, ≥2 immunomodulatory agents, and 1 anti-CD38 antibody.

Efficacy


CARTITUDE-1: Efficacy Outcomes in Key Subgroups at a Median Follow-Up of 27.7 Months1
Overall
3 Prior LOT
≥4 Prior LOT
Triple-Class Refractory
Penta-Drug Refractory
Patients,
n (%)
97
(100)
17
(18)
80
(82)
85
(88)
41
(42)
ORR, % (95% CI)
97.9
(92.7-99.7)
100.0
(80.5-100)
97.5
(91.3-99.7)
97.6
(91.8-99.7)
95.1
(83.5-99.4)
Median DOR,
months (95% CI)
NE
(23.3-NE)
NE
(12.9-NE)
28.3
(23.3-NE)
NE
(24.3-NE)
NE
(24.4-NE)
MRD 10-5 negativitya, n (%)
56/61
(91.8)
8
(80.0)
48
(94.1)
50
(92.6)
17
(85.0)
Median PFS,
(95% CI)
NE
(24.5-NE)
NE
(13.8-NE)
30.1
(24.5-NE)
NE
(25.2-NE)
NE
(25.3-NE)
27-month PFS, % (95% CI)
54.9
(44.0-64.6)
56.7
(30.0-76.6)
54.0
(41.7-64.8)
55.6
(43.8-65.9)
61.6
(44.0-75.1)
27-month OS, % (95% CI)
70.4
(60.1-78.6)
76.5
(48.8-90.4)
69.0
(57.3-78.1)
69.7
(58.4-78.5)
66.8
(49.3-79.4)
Abbreviations: CI, confidence interval; CR, complete response; DOR, duration of response; LOT, line of therapy; MRD, minimal residual disease; NE, not estimable; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; sCR, stringent complete response.
aIn MRD-evaluable patients, MRD was assessed in evaluable samples at a 10-5 threshold by next-generation sequencing (clonoSEQ®) in all treated patients at day 28, and at 6, 12, 18, and 24 months regardless of the status of disease measured in blood or urine. Only MRD assessments (10-5 testing threshold) within 3 months of achieving CR/sCR until death/progression/subsequent therapy (exclusive) are considered.

CARTITUDE-1: Demographics and Disease Characteristics by ≥5-Year Progression Free Status3
Characteristic
≥5 Years Alive and
Progression-Free
(n=32)
PD Within 5 Years
(n=46)
≥5 Years Progression-Free vs PD Within 5 Years, P Valuea
Median age, years (range)
60.0 (43-78)
61.5 (47-77)
0.515
Sex
0.650
   Male (%)
53.1
58.7
-
Previous LOT, median (range)
6.5 (3-14)
5.0 (3-18)
0.58
Triple-classb refractory, n (%)
29 (90.6)
39 (84.8)
0.513
Penta-drugc refractory, n (%)
15 (46.9)
15 (32.6)
0.241
Time from start of last LOT to progression on that line, months, median (range)
3.98 (0.7-48.6)d
3.89
(0.7-21.5)e
-
Abbreviations: IMiD, immunomodulatory drug; LOT, line of therapy; PD, progressive disease; PI, proteasome inhibitor.
aP values were calculated by using Fisher’s test for categorical variables and Wilcoxon test for numerical variables without multiplicity adjustments.
b≥1 PI, ≥1 IMiD, and one anti-CD38 antibody.
c≥2 PIs, ≥2 IMiDs, and one anti-CD38 antibody.
dn=29.
en=42

Safety

  • The incidence of CRS, ICANS, and other CAR-T cell neurotoxicities (events not reported as ICANS) in subgroups was consistent with the overall population.4

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 (physician's choice of DPd or PVd) in adult patients with lenalidomide-refractory MM after 1-3 prior LOTs.5,6

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 LOTs including a PI and an immunomodulatory drug
    • Refractory to lenalidomide
    • No prior exposure to CAR-T or BCMA targeting therapy
  • Primary endpoint: PFS

Results

Treatment Disposition, 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
    • All 208 patients randomized to the CARVYKTI arm received bridging therapy with either DPd (n=182) or PVd (n=26). A total of 176 patients (84.6%) received CARVYKTI as study treatment (as-treated population). In the as-treated population, 21.6% of patients received 1 bridging therapy cycle, 58.5% of patients received 2 bridging therapy cycles, and 19.9% of patients received 3-6 bridging therapy cycles.5,10
  • Patient details and a summary of prior therapies for the intent-to-treat (ITT) population are presented in Table: CARTITUDE-4: Select Demographics and Disease Characteristics (ITT Population).
    • The median number of prior LOTs in both the CARVYKTI and standard care arms was 2 (range, 1-3).7
  • Patient details and a summary of prior therapies for the as-treated population are presented in Table: CARTITUDE-4: Select Demographics and Disease Characteristics (As-treated Population).

CARTITUDE-4: Select Demographics and Disease Characteristics (ITT Population)5,7,8,11
Characteristic
CARVYKTI
(n=208)
Standard Care
(n=211)
Age, median (IQR), years
61.5 (52-68)
61.0 (53-68)
Prior LOT, n (%)
   1
68 (32.7)
68 (32.2)
   2
83 (39.9)
87 (41.2)
   3
57 (27.4)
56 (26.5)
Prior immunomodulatory drugs, n (%)
208 (100.0)
211 (100.0)
   Lenalidomide
208 (100.0)
211 (100.0)
   Pomalidomide
8 (3.8)
10 (4.7)
Prior anti-CD38 antibody, n (%)
53 (25.5)
55 (26.1)
   Daratumumab
51 (24.5)
54 (25.6)
   Isatuximab
2 (1.0)
2 (0.9)
Prior PIs, n (%)
208 (100.0)
211 (100.0)
   Bortezomib
203 (97.6)
205 (97.2)
   Carfilzomib
77 (37.0)
66 (31.3)
   Ixazomib
21 (10.1)
21 (10.0)
Triple-class exposeda, n (%)
53 (25.5)
55 (26.1)
Penta-drug exposedb,n (%)
14 (6.7)
10 (4.7)
Refractory status, n (%)
   Lenalidomide
208 (100.0)
211 (100.0)
   Bortezomib
55 (26.4)
48 (22.7)
   Carfilzomib
51 (24.5)
45 (21.3)
   Any anti-CD38 antibody
50 (24.0)
46 (21.8)
   Daratumumab
48 (23.1)
45 (21.3)
   Ixazomib
15 (7.2)
17 (8.1)
   Pomalidomide
8 (3.8)
9 (4.3)
   Triple-class refractorya
30 (14.4)
33 (15.6)
   Penta-drug refractoryb
2 (1.0)
1 (0.5)
Abbreviations: CD38, cluster of differentiation 38; ITT, intent-to-treat; IQR, interquartile range; LOT, line of therapy; PI, proteasome inhibitor.
aIncluding 1 PI, 1 immunomodulatory drug, and 1 anti-CD38 antibody.
bIncluding ≥2 PIs, ≥2 immunomodulatory drugs, and 1 anti-CD38 antibody.

CARTITUDE-4: Select Demographics and Disease Characteristics (As-treated Population)8,10
Characteristic
As-treated Population
(n=176)
Median age, years (range)
61 (27-78)
Number of prior LOT, n %
   1
60 (34.1)
   2
66 (37.5)
   3
50 (28.4)
Treatment refractoriness, n (%)
   Triple-class refractorya
20 (11.4)
   Not triple-class refractory
156 (88.6)
Treatment history, n (%)
   Prior daratumumab exposed
36 (20.5)
   Prior triple-class exposeda
37 (21.0)
Abbreviations: LOT, line of therapy; PI, proteasome inhibitor.
aIncluding 1 PI, 1 immunomodulatory drug, and 1 anti-CD38 monoclonal antibody.

PFS in CARTITUDE-4 Subgroups of Patients with High-Risk Disease Features

  • PFS was analyzed in subgroups of patients with high-risk disease features in both the ITT and as-treated populations in the CARTITUDE-4 study.5,8

Results

Efficacy

ITT Population
As-treated Population
  • At a median follow-up of 16.0 months after randomization (range, 3.8-27.3), 12-month PFS rate in the as-treated population (n=176) remained >82% in the presence of common markers of poor prognosis including triple-class refractoriness. Twelve-month PFS rates for these select patient groups are presented in Table: CARTITUDE-4: PFS Analysis in Select Subgroups Related to Treatment History (As-treated Population) .8
  • Data in patients with prior daratumumab or triple-class exposure showed CARVYKTI was effective in this population.8

CARTITUDE-4: PFS Analysis in Select Subgroups Related to Treatment History (ITT Population)8
Characteristic
Median PFS, Months (95% CI)
Hazard Ratioa
(95% CI)
CARVYKTI
(n=208)
SOC
(n=211)
Number of prior LOT
   1
NR (NE-NE)
17.4 (11.1-NE)
0.35 (0.19-0.66)
   2 or 3
NR (19.2-NE)
10.2 (6.2-12.2)
0.24 (0.16-0.37)
Refractory to
   PI + immunomodulatory drug
22.8 (18.0-NE)
7.8 (4.7-11.5)
0.24 (0.14-0.38)
   Anti-CD38 + immunomodulatory drug
18.0 (9.3-22.8)
4.3 (3.4-5.7)
0.26 (0.14-0.50)
   Triple-classb
19.3 (2.6-NE)
4.1 (3.1-7.8)
0.15 (0.05-0.39)
   Neither anti-CD38 nor PI
NR (NE-NE)
17.41 (12.0-22.4)
0.20 (0.10-0.39)
   Last line of prior therapy
NR (22.8-NE)
11.8 (9.7-14.0)
0.27 (0.19-0.39)
Prior exposure to
   Daratumumab
19.2 (9.7-NE)
4.5 (3.6-7.5)
0.23 (0.12-0.44)
   Bortezomib
NR (22.8-NE)
11.9 (9.8-14.0)
0.27 (0.19-0.39)
   Triple-classb
19.2 (9.7-NE)
4.7 (3.6-7.5)
0.26 (0.14-0.48)
Bridging therapy/SOC
   PVd
11.7 (2.1-NE)
5.0 (3.4-10.5)
0.31 (0.13-0.72)
   DPd
NR (22.8-NE)
12.5 (10.3-16.0)
0.26 (0.18-0.39)
Abbreviations: CD38, cluster of differentiation 38; CI, confidence interval; DPd, daratumumab, pomalidomide, and dexamethasone; ITT, intent-to-treat; LOT, line of therapy; NE, not estimable; NR, not reached; PFS, progression-free survival; PI, proteasome inhibitor; PVd, pomalidomide, bortezomib, and dexamethasone; SOC, standard of care.
aHazard ratio and 95% CI from a Cox proportional hazards model with treatment as the sole explanatory variable, including only PFS events that occurred >8 weeks after randomization. A hazard ratio <1 indicates an advantage for the CARVYKTI arm.
bPI + immunomodulatory drug + anti-CD38 antibody.

CARTITUDE-4: PFS Analysis in Select Subgroups Related to Treatment History (As-treated Population)8
Characteristic
CARVYKTI (n=176)
12-Month PFS, % (95% CI)
Refractoriness
   Not triple-class refractory
89.7 (83.7-93.5)
   Triple-class refractorya
90.0 (65.6-97.4)
Treatment history
   All patients
84.9 (78.2-89.7)
   Daratumumab exposed
82.8 (65.7-91.9)
   Triple-class exposeda
83.3 (66.5-92.1)
Abbreviations: CD38, cluster of differentiation 38; CI, confidence interval; PFS, progression-free survival; PI, proteasome inhibitor.
aPI + immunomodulatory drug + anti-CD38 antibody.

Safety

  • Safety outcomes in select subgroups related to treatment history in both the ITT and as-treated population in the CARTITUDE-4 study have not yet been reported.

CARTITUDE-4 Subgroup Analysis in Patients with Functional High-Risk MM

  • Efficacy and safety outcomes were evaluated in patients who received 1 prior LOT, including the subset of patients with functionally high-risk MM, in the CARTITUDE-4 study.9 

Results

Patient Demographics and Disease/Treatment Characteristics

  • A total of 136 patients received 1 prior LOT in the CARTITUDE-4 study.9 
    • In the CARVYKTI arm, 68 patients underwent apheresis/bridging therapy; 40 patients had functionally high-risk MM. Of the 68 patients, 60 received CARVYKTI as study treatment; 35 patients had functionally high-risk MM.
    • A total of 68 patients received standard care; 39 of these patients had functionally high-risk MM.
    • Functionally high-risk MM defined as progressive disease (PD) ≤18 months after receiving autologous stem cell transplant (ASCT) or the start of initial frontline therapy in patients with no ASCT.
  • Patient details and a summary of prior therapies for these subgroups are presented in Table: CARTITUDE-4: Baseline Demographics and Disease Characteristics of Patients With 1 Prior LOT and Those With 1 Prior LOT and Functionally High-Risk MM.9 

CARTITUDE-4: Baseline Demographics and Disease Characteristics of Patients With 1 Prior LOT and Those With 1 Prior LOT and Functionally High-Risk MM9 
Characteristic
1 Prior LOT
1 Prior LOT and Functionally High-Risk MM
CARVYKTI
(n=68)
Standard Care
(n=68)
CARVYKTI
(n=40)
Standard Care
(n=39)
Age, median (range), years
60.5 (27-78)
60.0 (35-78)
60.0 (27-71)
60.0 (40-78)
Male, n (%)
36 (52.9)
42 (61.8)
18 (45.0)
27 (69.2)
ISS stage II/IIIa,n (%)
20 (29.4)
22 (32.4)
12 (30.0)
14 (35.9)
Prior ASCT, n (%)
56 (82.4)
60 (88.2)
33 (82.5)
33 (84.6)
Prior anti-CD38 antibody exposureb, n (%)
2 (2.9)
3 (4.4)
2 (5.0)
1 (2.6)
High-risk cytogeneticsc, n (%)
39 (57.4)
45 (66.2)
22 (55.0)
27 (69.2)
   del17p
14 (20.6)
15 (22.1)
9 (22.5)
9 (23.1)
   t(4;14)
13 (19.1)
10 (14.7)
8 (20.0)
6 (15.4)
   t(14;16)
1 (1.5)
3 (4.4)
0
2 (5.1)
   Gain/amp(1q)
34 (50.0)
38 (55.9)
20 (50.0)
23 (59.0)
   With ≥2 high-risk abnormalities
20 (29.4)
20 (29.4)
13 (32.5)
12 (30.8)
High tumor burdenc,n (%)
9 (13.2)
8 (11.8)
5 (12.5)
4 (10.3)
Soft tissue plasmacytomad,n (%)
12 (17.6)
7 (10.3)
6 (15.0)
4 (10.3)
Abbreviations: ASCT, autologous stem cell transplant; CD, cluster of differentiation; ISS, International Staging System; LOT, line of therapy; MM, multiple myeloma.
aBased on serum β2-microglobulin and albumin.
bPer study design, all patients had also received a proteosome inhibitor and immunomodulatory drug, ie, those with anti-CD38 antibody exposure were triple class exposed.
cHigh- risk cytogenetics was defined as any of the following 4 cytogenetic features abnormal: del17p, t(14;16), t(4;14), or gain/amp(1q).
dHigh tumor burden defined as meeting any of the following criteria at baseline: ≥80% bone marrow plasma cells, ≥5 g/dL serum M protein level, or ≥5000 mg/L serum free light chain.
eSoft tissue plasmacytomas include extramedullary and bone-based plasmacytomas with a measurable soft tissue component.

Efficacy


CARTITUDE-4: Efficacy Outcomes in CARVYKTI vs Standard Care Patients With 1 Prior LOT and Those With 1 Prior LOT and Functionally High-Risk MM9 
Responsea
1 Prior LOT
1 Prior LOT and Functionally
High-Risk MM
CARVYKTI(n=68)
Standard Care
(n=68)
Odds Ratio
(95% CI)
CARVYKTI
(n=40)
Standard Care
(n=39)
Odds Ratio
(95% CI)
ORRb, %
89.7
79.4
-
87.5
79.5
-
   sCR
52.9
23.5
-
45.0
28.2
-
   CR
17.6
11.8
-
22.5
10.3
-
   VGPR
11.8
23.5
-
12.5
15.4
-
   PR
7.4
20.6
-
7.5
25.6
-
≥CR, %
70.6
35.3
4.4
(2.1-9.0)c,d
67.5
38.5
3.3
(1.3-8.4)c,e
MRD-negativity
(10-5)f, %
63.2
19.1
7.3
(3.3-15.9)c,g
65.0
10.3
16.3
(4.8-55.1)c,g
Median DORh,i, months (95% CI)
NR
(NE-NE)
19.81
(14.06-NE)
-
NR
(15.70-NE)
16.36
(8.31-NE)
-
   12-month DOR
   rate, % (95% CI)
81.8
(68.4-89.9)
68.8
(54.0-79.6)
-
79.5
(59.0-90.5)
55.8
(36.1-71.7)
-
Median PFSh
months (95% CI)
NR
(NE-NE)j,k,l
17.41
(11.10-NE) j,k,l
-
NR
(18.00-NE)k,l,m
11.79
(8.44-NE) k,l,m
-
   12-month PFS
   rate, % (95% CI)
77.7
(65.8-85.9)
58.5
(45.5-69.4)
-
77.0
(60.3-87.3)
49.1
(32.4-63.8)
-
Abbreviations: CI, confidence interval; CR, complete response; DOR, duration of response; HR, hazard ratio; IMWG, International Myeloma Working Group; LOT, line of therapy; MM, multiple myeloma; MRD, minimal residual disease; NE, not estimable; NR, not reached; ORR, overall response rate; PD, progressive disease; PFS, progression-free survival; PR, partial response; sCR, stringent complete response; VGPR, very good partial response.aTreatment response was assessed by a validated computerized algorithm, based on IMWG consensus criteria. bORR was defined as the proportion of patients who achieve a PR or better.
cMantel-Haenszel estimate of the common odds ratio for unstratified tables is used.
dP<0.0001; P value was calculated using the Cochran-Mantel-Haenszel Chi-squared test.
eP=0.0102; P value was calculated using the Cochran-Mantel-Haenszel Chi-squared test.
fMRD-negativity (10-5 threshold) was based on next-generation sequencing and post randomization assessment. Overall rate reflects patients with MRD-negativity by bone marrow aspirate at any time after the randomization date and before PD or subsequent antimyeloma treatment.
gP<0.0001; P value was calculated using the Fisher’s exact test.
hAssessed using a validated computerized algorithm.
iDetermined among responders.
jHR (95% CI): 0.35 (0.19-0.66); P=0.0007.
kHR and 95% CI from a Cox proportional hazards model with treatment as the sole explanatory variable, including only PFS events that occurred >8 weeks after randomization.
lP value based on the constant piecewise weighted log-rank test, where the weight equals 0 in the log-rank statistic for the first 8 weeks after randomization and 1 week afterward.
mHR (95% CI): 0.27 (0.12-0.60); P=0.0006.

CARTITUDE-4: Efficacy Outcomes in CARVYKTI As-Treated Patients With 1 Prior LOT and Those With 1 Prior LOT and Functionally High-Risk MM9 
Responsea
1 Prior LOT
(n=60)
1 Prior LOT and Functionally High-Risk MM
(n=35)
ORRb, %
100
100
   sCR
60.0
51.4
   CR
20.0
25.7
   VGPR
13.3
14.3
   PR
6.7
8.6
≥CR, %
80.0
77.1
MRD-negativity (10-5)c, n (%)
43 (71.6)
26 (74.3)
Median PFS, months (95% CI)
NR (NE-NE)
NR (18.0-NE)
   12-month PFS, % (95% CI)
88.1 (76.6-94.1)
88.0 (70.9-95.3)
Abbreviations: CI, confidence interval; CR, complete response; IMWG, International Myeloma Working Group; LOT, line of therapy; MM, multiple myeloma; MRD, minimal residual disease; NE, not estimable; NR, not reached; ORR, overall response rate; PD, progressive disease; PFS, progression-free survival; PR, partial response; sCR, stringent complete response; VGPR, very good partial response.
aTreatment response was assessed by a validated computerized algorithm based on IMWG consensus criteria.
bORR was defined as the proportion of patients who achieve a PR or better.
cMRD-negativity (10-5 threshold) was based on next generation sequencing and post randomization assessment. Overall rate reflects patients with MRD-negativity by bone marrow aspirate at any time after the randomization date and before PD or subsequent antimyeloma treatment.

Safety

  • Similar rates of grade ≥3 and serious treatment emergent adverse events (TEAEs) were observed between patients with 1 prior LOT and those with 1 prior LOT and functionally high-risk MM. See Table: CARTITUDE-4: Frequency of AEs in Patients With 1 Prior LOT and Those With 1 Prior LOT and Functionally High-Risk MM.9 
  • Adverse events (AEs) of special interest observed in subgroups of patients with 1 prior LOT and functionally high-risk MM are summarized in Table: CARTITUDE-4: AEs of Special Interest in CARVYKTI Patients With 1 Prior LOT and Those With 1 Prior LOT and Functionally High-Risk MM.9 
  • Second primary malignancy occurred in 3 patients in the CARVYKTI arm and in 2 patients in the standard care arm among those with 1 prior line; all occurred in patients with functionally high-risk MM (one patient in the CARVYKTI arm had peripheral T-cell lymphoma unspecified).9 
  • In patients with 1 prior LOT, 11 deaths were reported in each CARVYKTI arm and the standard care arm. Of these, 7 patients in the CARVYKTI arm and 9 patients in the standard care arm died and had functionally high-risk MM.9 
    • Among the 7 patients that died in the CARVYKTI arm, death occurred in 2 patients that did not receive CARVYKTI as study treatment and in 3 patients that received CARVYKTI as subsequent therapy.

CARTITUDE-4: Frequency of AEs in Patients With 1 Prior LOT and Those With 1 Prior LOT and Functionally High-Risk MM9 
1 Prior LOT
1 Prior LOT and Functionally High-Risk MM
CARVYKTI
(n=68)
Standard Care
(n=68)
CARVYKTI
(n=40)
Standard Care
(n=39)
Grade ≥3 TEAEs, n (%)
65 (95.6)
65 (95.6)
40 (100.0)
38 (97.4)
Serious TEAEs, n (%)
26 (38.2)
24 (35.3)
16 (40.0)
13 (33.3)
Abbreviations: AE, adverse event; LOT, line of therapy; MM, multiple myeloma; TEAE, treatment-emergent adverse event.

CARTITUDE-4: AEs of Special Interest in CARVYKTI Patients With 1 Prior LOT and Those With 1 Prior LOT and Functionally High-Risk MM9 
AEsa, n (%)
1 Prior LOT

1 Prior LOT and Functionally High-Risk MM

CARVYKTI
(n=68)
CARVYKTI
(n=68)
CARVYKTI
(n=40)
CARVYKTI
(n=40)
All
Grade 3 or 4
All
Grade 3 or 4
CRSb
44 (64.7)
1 (1.5)
25 (62.5)
0
ICANSc
2 (2.9)
0
2 (5.0)
0
Cranial nerve palsy
6 (8.8)
2 (2.9)
3 (7.5)
0
Movement and neurocognitive TEAEs
1 (1.5)
0
0
0
Peripheral neuropathy
2 (2.9)
0
2 (5.0)
0
Abbreviations: AE, adverse event; ASTCT, American Society for Transplantation and Cellular Therapy; CRS, cytokine release syndrome; ICANS, immune effector cell-associated neurotoxicity syndrome; LOT, line of therapy; MM, multiple myeloma; NCI-CTCAE, National Cancer Institute Common Terminology Criteria for Adverse Events, TEAE, treatment-emergent adverse event.
aAEs of special interest were evaluated in all patients receiving CARVYKTI as second-line treatment (n=68) and in those with functionally high-risk MM status (n=40). AEs were graded per NCI-CTCAE criteria version 5.0.
bCRS was assessed per ASTCT criteria.
cICANS was assessed per ASTCT criteria.

Interim Analysis (33.6 months)

Efficacy

ITT Population

CARTITUDE-4: OS With CARVYKTI vs Standard Care Across Subgroups6
Characteristic

CARVYKTI
Standard care
HRa
(95% CI)
Events/patients
Median
(95% CI)
Events/patients
Median
(95% CI)
Number of prior LOTs
   1
13/68
NE (NE-NE)
23/68
NE (37.7-NE)
0.56 (0.28-1.11)
   2 or 3
37/140
NE (NE-NE)
60/143
NE (31.0-NE)
0.57 (0.38-0.86)
Refractory to
   PI + IMiD
28/103
NE (NE-NE)
45/96
34.7 (21.4-NE)
0.51 (0.32-0.82)
   Anti-CD38 + IMiD
18/50
NE (23.1-NE)
22/46
34.0 (16.5-NE)
0.70 (0.37-1.30)
   PI + anti-CD38 + IMiD
9/30
NE (NE-NE)
17/33
34.0 (14.9-NE)
0.53 (0.24-1.20)
   Last line of prior
   therapy
48/205
NE (NE-NE)
82/208
NE (37.7-NE)
0.55 (0.39-0.79)
Prior exposure to
   Daratumumab
17/51
NE (NE-NE)
27/54
34.0 (16.4-NE)
0.61 (0.33-1.12)
   Bortezomib
47/203
NE (NE-NE)
81/205
NE (37.7-NE)
0.55 (0.38-0.78)
   Bortezomib and
   daratumumab
15/48
NE (NE-NE)
26/50
26.7 (16.4-NE)
0.53 (0.28-1.00)
Daratumumab naïve
   Yes
33/157
NE (NE-NE)
56/157
NE (37.7-NE)
0.56 (0.36-0.86)
   No
17/51
NE (NE-NE)
27/54
34.0 (16.4-NE)
0.61 (0.33-1.12)
Abbreviations: CD, cluster of differentiation; CI, confidence interval; HR, hazard ratio; IMiD, immunomodulatory drug; LOT, line of therapy; OS, overall survival; PI, proteasome inhibitor.
aHRs and 95% CIs from a Cox proportional hazards model with treatment as the sole explanatory variable.

CARTITUDE-4: PFS With CARVYKTI vs Standard Care Across Subgroups6   
Characteristic

CARVYKTI
Standard care
HRa
(95% CI)
Events/patients
Median
(95% CI)
Events/patients
Median
(95% CI)
Number of prior LOTs
   1
28/68
NE (27.8-NE)
45/68
17.4 (11.1-26.7)
0.41 (0.25-0.67)
   2 or 3
61/140
NE (29.9-NE)
108/143
10.2 (6.2-12.2)
0.26 (0.18-0.37)
Refractory to
   PI + IMiD
49/103
37.1 (23.0-NE)
75/96
7.8 (4.7-11.5)
0.25 (0.17-0.38)
   Anti-CD38 + IMiD
31/50
19.2 (9.3-34.5)
41/46
4.3 (3.4-5.7)
0.25 (0.14-0.44)
   PI + anti-CD38 + IMiD
17/30
22.9 (2.6-NE)
29/33
4.1 (3.1-7.8)
0.17 (0.08-0.38)
   Last line of prior
   therapy
86/205
NE (34.5-NE)
151/208
11.9 (9.7-14.0)
0.30 (0.22-0.40)
Prior exposure to
   Daratumumab
30/51
19.3 (9.7-NE)
47/54
4.5 (3.6-7.5)
0.24 (0.14-0.42)
   Bortezomib
85/203
NE (34.5-NE)
147/205
11.9 (9.8-14.0)
0.30 (0.22-0.40)
   Bortezomib and
   daratumumab
27/48
22.3 (9.7-NE)
43/50
4.7 (3.6-7.5)
0.24 (0.13-0.43)
Daratumumab naïve
   Yes
59/157
NE (37.1-NE)
106/157
14.0 (11.8-19.8)
0.31 (0.22-0.44)
   No
30/51
19.3 (9.7-NE)
47/54
4.5 (3.6-7.5)
0.24 (0.14-0.42)
Abbreviations: CD, cluster of differentiation; CI, confidence interval; HR, hazard ratio; IMiD, immunomodulatory drug; LOT, line of therapy; PFS, progression-free survival; PI, proteasome inhibitor.
aHRs and 95% CIs from a Cox proportional hazards model with treatment as the sole explanatory variable, only PFS events that occurred more than 8 weeks after randomisation were included.

CARTITUDE-4: MRD Negativity Rates With CARVYKTI Across Subgroups12    
Characteristic

MRD Negativity
OR (95% CI)
Number of prior LOTs
   1
6.48 (3.03-13.84)
   2 or 3
7.66 (4.40-13.34)
Refractory to
   PI + IMiD
8.51 (4.31-16.76)
   Anti-CD38 + IMiD
13.23 (3.62-48.32)
   PI + anti-CD38 + IMiD
11.85 (2.39-58.82)
   Last line of prior therapy
7.44 (4.74-11.68)
Prior exposure to
   Daratumumab
25.00 (5.49-113.77)
   Bortezomib
7.19 (4.58-11.30)
   Bortezomib and daratumumab
22.08 (4.81-101.32)
Daratumumab naïve
   Yes
6.36 (3.88-10.44)
Abbreviations: CD, cluster of differentiation; CI, confidence interval; HR, hazard ratio; IMiD, immunomodulatory drug; LOT, line of therapy; MRD, minimal residual disease; OR, odds ratio; PI, proteasome inhibitor.

Safety

  • Safety outcomes specific to prior LOTs were not reported within the Interim Analysis (33.6 months).

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 02 March 2026.

 

References

Show
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