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CARVYKTI® (ciltacabtagene autoleucel)

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

Last Updated: 05/09/2025

Summary

CARTITUDE-1 (MMY2001) was a phase 1b/2 study that evaluated CARVYKTI in patients with relapsed/refractory multiple myeloma (RRMM) who had previously received a proteasome inhibitor (PI), an immunomodulatory agent, and an anti-cluster 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^-³
- Patients received a median of 6 (range, 3-18) prior lines of therapy (LOT); 88% of patients were triple-class refractory, 42% of patients were penta-drug refractory and 99% of patients were refractory to the last LOT.²
- 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 LOT and patients who were tripleclass or penta-drug refractory.²^,⁴
- 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 (MMY3002) is a phase 3 study evaluating the efficacy and safety of CARVYKTI vs standard care (physician’s choice of pomalidomide, bortezomib, and dexamethasone [PVd] or DARZALEX FASPRO^® [daratumumab and hyaluronidase], pomalidomide, and dexamethasone [DPd]) in adult patients with lenalidomide-refractory multiple myeloma (MM) after 1-3 prior LOT.⁵^,⁶
- Patients received a median of 2 (range, 1-3) prior LOT in both the CARVYKTI and standard care arms.⁷
- From the primary analysis, the following subgroup analyses were conducted from the CARTITUDE-4 study that included results from select subgroups related to treatment history:
  - PFS in subgroups of patients with high-risk disease features.⁸
  - Subgroup analysis in patients with functional high-risk MM.⁹
- An Interim Analysis (33.6 months) was conducted from the CARTITIUDE-4 study that included results from select subgroups related to treatment history.¹⁰^,¹¹
  - Data on overall survival (OS), progression-free survival (PFS), and minimal-residual disease (MRD)-negativity status across select prespecified subgroups are detailed in Table: CARTITUDE-4: Efficacy - OS, PFS, and MRD-Negativity Rates with CARVYKTI Compared to Standard Care Across Select Subgroups – Interim Analysis.

PRODUCT LABELING

CARVYKTI (ciltacabtagene autoleucel) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.;http://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, 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^-³

Study Design/Methods

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

CARTITUDE-1 Study Design¹^,¹²^,¹³

A screenshot of a medical information

Description automatically generated

Abbreviations: CAR, chimeric antigen receptor; CD38, cluster of differentiation 38; cilta-cel, ciltacabtagene autoleucel; CR, complete response; Cy, cyclophosphamide; DOR, duration of response; ECOG PS, Eastern Cooperative Oncology Group performance status; Flu, fludarabine; IMWG, International Myeloma Working Group; MM, multiple myeloma; MRD, minimal residual disease; ORR, overall response rate; OS, overall survival; PD, pharmacodynamics; PFS, progression-free survival; PI, proteasome inhibitor; PK, pharmacokinetics; RP2D, recommended phase 2 dose; sCR, stringent complete response; VGPR, very good partial response.
^aTreatment with previously used agent resulting in at least stable disease.
^bIncluding a long-term, 15-year follow-up on a separate study.

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^-³ Patient details are presented in Table: CARTITUDE-1: Select Demographics and Disease Characteristics.
Patients received a median of 6 prior LOT (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.²^-⁴

CARTITUDE-1: Select Demographics and Disease Characteristics¹^-⁴

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 exposed^b, n (%)	97 (100)
Triple-class refractory, n (%)	85 (88)
Penta-drug exposed^c,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. ^a Additionally, 2 more patients were refractory to other anti-CD38 antibodies. ^b At least 1 PI, 1 immunomodulatory agent, and 1 anti-CD38 antibody. ^c≥2 PIs, ≥2 immunomodulatory agents, and 1 anti-CD38 antibody.

Efficacy

Efficacy outcomes in key subgroups of patients are presented in Table: CARTITUDE 1: Efficacy Outcomes in Key Subgroups at a Median Follow-Up of 27.7 Months.
After a median follow-up of 21.7 months and 27.7 months, responses were observed in most patients in high-risk subgroups (ORR range, 95.1%-100%) including patients with 3 or ≥4 prior LOT and patients who were tripleclass or penta-drug refractory.²^,⁴

CARTITUDE-1: Efficacy Outcomes in Key Subgroups at a Median Follow-Up of 27.7 Months²

	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^-5negativity^a, 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.

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 (MMY3002; NCT04181827) is an ongoing, phase 3, randomized, open-label study evaluating the efficacy and safety of CARVYKTI vs standard care (physician’s choice of PVd or DPd) in adult patients with lenalidomide-refractory MM after 1-3 prior LOT.⁵

Study Design/Methods

The study design is shown in Figure: CARTITUDE-4 Study Design.

CARTITUDE-4 Study Design⁵^,¹⁴

A screenshot of a computer

Description automatically generated

Abbreviations: BCMA, B-cell maturation antigen; CAR, chimeric antigen receptor; CAR-T, chimeric antigen receptor-T cell; cilta-cel, ciltacabtagene autoleucel; CR, complete response; Cy, cyclophosphamide; DPd, daratumumab, pomalidomide, and dexamethasone; ECOG, Eastern Cooperative Oncology Group; Flu, fludarabine; IMWG, International Myeloma Working Group; ISS, international staging system; IV, intravenous; LOT, line of therapy; MM, multiple myeloma; MRD, minimal residual disease; ORR, overall response rate; OS, overall survival; PI, proteasome inhibitor; PFS, progression-free survival; PK, pharmacokinetics; PRO, patient-reported outcome; PVd, pomalidomide, bortezomib, and dexamethasone.
^aRandomization was stratified by choice of PVd vs DPd, ISS stage at screening (I vs II vs III), and number of prior LOT (1 vs 2-3).
^bTreatment with PVd or DPd was continued until disease progression, death, intolerable toxicity, withdrawal of consent, or end of the study, whichever occurred earlier.
^cSecondary outcomes were sequentially tested at each prespecified significance level, including (in order) rates of CR or better, OR, MRD negativity, OS, and time to patient-reported symptom worsening as assessed by the MM Symptom and Impact Questionnaire.

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^,⁶
Patient details and a summary of prior therapies for the ITT population are presented in Table: CARTITUDE-4: Select Demographics and Disease Characteristics (ITT Population).
- The median number of prior LOT 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

Characteristic	CARVYKTI (n=208)	Standard Care (n=211)
Age, median (range), years	61.5 (27-78)	61.0 (35-80)
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 exposed^a, n (%)	53 (25.5)	55 (26.1)
Penta-drug exposed^b,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 refractory^a	30 (14.4)	33 (15.6)
Penta-drug refractory^b	2 (1.0)	1 (0.5)
Abbreviations: CD38, cluster of differentiation 38; ITT, intent-to-treat; 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)⁶^,⁸

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 refractory^a	20 (11.4)
Not triple-class refractory	156 (88.6)
Treatment history, n (%)
Prior daratumumab exposed	36 (20.5)
Prior triple-class exposed^a	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

At a median follow-up of 15.9 months (range, 0.1-27.3), CARVYKTI (n=208) demonstrated improved PFS vs standard care (n=211) in all analyzed subgroups in the ITT population. PFS in this population based on treatment history is presented in Table: CARTITUDE-4: PFS Analysis in Select Subgroups Related to Treatment History (ITT Population).⁸

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 Ratio^a(95% CI)
Characteristic	CARVYKTI (n=208)	SOC (n=211)	Hazard Ratio^a(95% CI)
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-class^b	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-class^b	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 refractory^a	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 exposed^a	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 has 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
Characteristic	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/III^a,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 exposure^b, n (%)	2 (2.9)	3 (4.4)	2 (5.0)	1 (2.6)
High-risk cytogenetics^c, 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 burden^c,n (%)	9 (13.2)	8 (11.8)	5 (12.5)	4 (10.3)
Soft tissue plasmacytoma^d,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

Efficacy was evaluated at a median follow-up of 15.9 months (range, 0.1-27.3).⁹
Efficacy outcomes for the subgroups are provided in the following Tables:⁹
- Table: CARTITUDE-4: Efficacy Outcomes in CARVYKTI vs Standard Care Patients With 1 Prior LOT and Those With 1 Prior LOT and Functionally High-Risk MM.
- Table: CARTITUDE-4: Efficacy Outcomes in CARVYKTI As-Treated Patients With 1 Prior LOT and Those With 1 Prior LOT and Functionally High-Risk MM.

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

Response^a	1 Prior LOT			1 Prior LOT and Functionally High-Risk MM
Response^a	CARVYKTI (n=68)	Standard Care (n=68)	Odds Ratio (95% CI)	CARVYKTI (n=40)	Standard Care (n=39)	Odds Ratio (95% CI)
ORR^b, %	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 DOR^h,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 PFS^h 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

Response^a	1 Prior LOT (n=60)	1 Prior LOT and Functionally High-Risk MM (n=35)
ORR^b, %	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 advserse 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 (SPM) 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

AEs^a, 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
CRS^b	44 (64.7)	1 (1.5)	25 (62.5)	0
ICANS^c	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

At the data cut-off date of May 1, 2024, 117 CARVYKTI patients were ongoing in the post-treatment phase and 43 patients were ongoing on standard care therapy.¹⁰
Data on OS, PFS, and MRD-negativity status across select prespecified subgroups are detailed in Table: CARTITUDE-4: Efficacy - OS, PFS, and MRD-Negativity Rates with CARVYKTI Compared to Standard Care Across Select Subgroups – Interim Analysis.¹⁰^,¹¹

CARTITUDE-4: Efficacy - OS, PFS, and MRD-Negativity Rates with CARVYKTI Compared to Standard Care Across Select Subgroups - Interim Analysis¹⁰^,¹¹

Characteristic	OS HR^a (95% CI)	PFS HR^b (95% CI)	MRD Negativity OR (95% CI)
Number of lines of prior therapy
1	0.56 (0.28-1.11)	0.41 (0.25-0.67)	6.48 (3.03-13.84)
2 or 3	0.57 (0.38-0.86)	0.26 (0.18-0.37)	7.66 (4.40-13.34)
Refractory to
PI + immunomodulatory drug	0.51 (0.32-0.82)	0.25 (0.17-0.38)	8.51 (4.31-16.76)
Anti-CD38 + immunomodulatory drug	0.70 (0.37-1.30)	0.25 (0.14-0.44)	13.23 (3.62-48.32)
PI + anti-CD38 + immunomodulatory drug	0.53 (0.24-1.20)	0.17 (0.08-0.38)	11.85 (2.39-58.82)
Last line of prior therapy	0.55 (0.39-0.79)	0.30 (0.22-0.40)	7.44 (4.74-11.68)
Prior exposure to
Daratumumab	0.61 (0.33-1.12)	0.24 (0.14-0.42)	25.00 (5.49-113.77)
Bortezomib	0.55 (0.38-0.78)	0.30 (0.22-0.40)	7.19 (4.58-11.30)
Bortezomib and daratumumab	0.53 (0.28-1.00)	0.24 (0.13-0.43)	22.08 (4.81-101.32)
Daratumumab naïve
Yes	0.56 (0.36-0.86)	0.31 (0.22-0.44)	6.36 (3.88-10.44)
No	0.61 (0.33-1.12)	0.24 (0.14-0.42)	-
Abbreviations: CI, confidence interval; HR, hazard ratio; MRD, minimal residual disease; OR, odds ratio; OS, overall survival; PFS, progression-free survival; PI, proteasome inhibitor. ^aHRs and 95% CIs from a Cox proportional hazards model with treatment as the sole explanatory variable. HR <1 indicates an advantage for the CARVYKTI arm. ^bHRs and 95% CIs from a Cox proportional hazards model with treatment as the sole explanatory variable, including only PFS events that occurred >8 weeks after randomization.

Safety

Safety outcomes specific to prior lines of therapy 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 May 2025.

References

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