CARTITUDE-4: A pivotal phase 3 study in patients as early as first relapse^1,2

CARTITUDE-4 is a randomized, open-label, multicenter controlled study in adult patients with relapsed and lenalidomide-refractory multiple myeloma, who previously received at least 1 prior line of therapy including a proteasome inhibitor and an immunomodulatory agent. A total of 419 patients were randomized 1:1 to receive either a sequence of apheresis, bridging therapy, lymphodepletion, and CARVYKTI® (n=208) or standard therapy which included daratumumab, pomalidomide, and dexamethasone (DPd) or pomalidomide, bortezomib, and dexamethasone (PVd) selected by physician prior to randomization based on patient’s prior antimyeloma therapy (n=211).

CARVYKTI® (ciltacabtagene autoleucel) CARTITUDE-4 study design, graphic

Primary Endpoint:
PFS (Intent-to-Treat)^†

Select Secondary Endpoints^||:
CR or better, ORR (sCR + CR + VGPR + PR), OS

CAR+=chimeric antigen receptor-positive; CR=complete response; IMWG=International Myeloma Working Group; IRC=Independent Review Committee; ISS=International Staging System; LoT=line(s) of therapy; len=lenalidomide; ORR=overall response rate; OS=overall survival; PFS=progression-free survival; PR=partial response; sCR=stringent complete response; VGPR=very good partial response.

*Randomization was stratified by physician’s choice of treatment (DPd vs PVd), ISS (I vs II vs III) and number of prior lines of therapy (1 vs 2 or 3).

^†Per the IMWG consensus, assessed by IRC.

^‡80.8% of patients received 1-2 cycles of standard therapy. Maximum received was 6 cycles in 1 patient.

^§The remaining 32 patients discontinued trial participation before receiving CARVYKTI®, predominantly because of disease
progression during bridging therapy or lymphodepletion. Of these patients, 20 received CARVYKTI® as a subsequent therapy.¹

^||Secondary outcomes were sequentially tested at each prespecified significance level, including (in order) rates of CR or better, ORR.²

CARVYKTI^® was studied in patients with 1-3 prior lines of therapy^1,2

CARTITUDE-4 study: Eligibility criteria^1,2

Key inclusion criteria

Adult patients with RRMM
Received 1-3 prior LoT including a PI
and an immunomodulatory agent
Refractory to lenalidomide
ECOG PS 0-1

Key exclusion criteria

Prior CAR-T or BCMA-targeting therapy
Known active or prior history of central nervous system involvement
Exhibit clinical signs of meningeal involvement of multiple myeloma
History of Parkinson’s disease or other neurodegenerative disorders

BCMA=B-cell maturation antigen; CAR-T=chimeric antigen receptor-T cell; ECOG PS=Eastern Cooperative Oncology Group performance status; LoT=line(s) of therapy; PI=proteasome inhibitor; RRMM=relapsed or refractory multiple myeloma.

CARTITUDE-4 study: Baseline characteristics (N=419)²

You are now viewing an analysis from the CARTITUDE-4 trial. This information is not included in the current USPI.

Characteristic	CARVYKTI^® (n=208)	Standard Therapy (n=211)
Median age, years (range)	61.5 (27–78)	61.0 (35–80)
Male, n (%)	116 (55.8)	124 (58.8)
Race or ethnic group, n (%)*
Asian	16 (7.7)	20 (9.5)
Black	6 (2.9)	7 (3.3)
White	157 (75.5)	157 (74.4)
Other	1 (0.5)	1 (0.5)
Missing data	28 (13.5)	26 (12.3)
Hispanic or Latino ethnic group, n (%)*
Hispanic or Latino	18 (8.7)	10 (4.7)
Not Hispanic or Latino	152 (73.1)	165 (78.2)
Missing data	38 (18.3)	36 (17.1)
Geographic region
Europe	128 (61.5)	129 (61.1)
North America	32 (15.4)	32 (15.2)
Asia	27 (13.0)	25 (11.8)
Australia	21 (10.1)	25 (11.8)
ECOG PS score, n (%)^†
0	114 (54.8)	121 (57.3)
1	93 (44.7)	89 (42.2)
2	1 (0.5)	1 (0.5)
ISS stage, n (%)
I	136 (65.4)	132 (62.6)
II	60 (28.8)	65 (30.8)
III	12 (5.8)	14 (6.6)
Median time since diagnosis, years (range)	3.0 (0.3–18.1)	3.4 (0.4–22.1)
Presence of soft-tissue plasmacytomas, n (%)^‡	44 (21.2)	35 (16.6)
Bone marrow plasma cells ≥60%, n/total n (%)^§	42/206 (20.4)	43/208 (20.7)
Cytogenetic risk, n/total n (%)
Standard	69/207 (33.3)	70/210 (33.3)
High^\|\|	123/207 (59.4)	132/210 (62.9)
Gain/amp(1q)	89/207 (43.0)	107/210 (51.0)
del(17p)	49/207 (23.7)	43/210 (20.5)
t(4;14)	30/207 (14.5)	30/210 (14.3)
t(14;16)	3/207 (1.4)	7/210 (3.3)
With ≥2 high-risk abnormalities	43/207 (20.8)	49/210 (23.3)
With del(17p), t(4;14), or t(14;16)	73/207 (35.3)	69/210 (32.9)
Missing data	15/207 (7.2)	8/210 (3.8)
Tumor BCMA expression ≥50%, n (%)	141 (67.8)	138 (65.4)
Prior lines of therapy, n (%)
1	68 (32.7)	68 (32.2)
2	83 (39.9)	87 (41.2)
3	57 (27.4)	56 (26.5)
Prior immunomodulatory agents, 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 proteasome inhibitor, 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, n (%)^¶	53 (25.5)	55 (26.1)
Penta-drug exposed, 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^¶	30 (14.4)	33 (15.6)
Penta-drug^#	2 (1.0)	1 (0.5)

amp=amplification; BCMA=B-cell maturation antigen; CD38=cluster of differentiation 38; del=deletion; ECOG PS=Eastern Cooperative Oncology Group performance status; Gain/amp=gain or amplification; ISS=International Staging System; t=translocation; USPI=US Prescribing Information.

*Race or ethnic group was reported by the patients. Among the patients who were enrolled in the United States, 9 (14.1%) were Black. The designation of “Other” includes American Indian and Alaska Native ethnic groups.

^†Listed is the latest available performance-status score on the Eastern Cooperative Oncology Group (ECOG) scale that was recorded on or before the initiation of apheresis or Cycle 1. All the patients met the inclusion criteria of an ECOG performance-status score of 0 or 1 before randomization.

^‡Soft-tissue plasmacytomas include extramedullary and bone-based plasmacytomas with a measurable soft-tissue component.

^§In the measurement of bone marrow plasma cells, the maximum value from bone marrow biopsy and bone marrow aspirate was selected if both results were available.

^‖High-risk cytogenetics, presence of t(4:14), (14:16), and 17p13 del, were present in 34% of patients.

^¶Triple-class therapy includes 1 proteasome inhibitor, 1 immunomodulatory agent, and 1 anti-CD38 monoclonal antibody.

^#Penta-drug therapy includes at least 2 proteasome inhibitors, at least 2 immunomodulatory agents, and 1 anti-CD38 monoclonal antibody.

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Progression–Free Survival (PFS)

Powerful results

CARTITUDE-4 PFS at 15.9 months

CARVYKTI^® significantly prolonged progression-free survival (primary endpoint) vs standard therapy (DPd or PVd)^1-3*

Progression-free survival

Percentages rounded to nearest whole number.

CI=confidence interval; DPd=daratumumab, pomalidomide, and dexamethasone; HR=hazard ratio; mPFS=median progression-free survival; NE=not estimable; PFS=progression-free survival; PVd=pomalidomide, bortezomib, and dexamethasone.

*Median follow-up was 15.9 months in the Intent-to-Treat Analysis Set.

Study Design
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Overall Survival (OS)

Overall survival

In CARTITUDE-4 at 15.9 Months¹*

In CARTITUDE-4 at 15.9 months, the interim analysis of overall survival (OS) did not meet criteria for statistical significance.

Overall survival in CARTITUDE-4 at 33.6 months¹

Longer follow-up at 33.6 months provides further insight into the OS outcomes in CARTITUDE-4.

View CARTITUDE-4 Follow-up Analysis

*Median follow-up was 15.9 months in the Intent-to-Treat Analysis Set.

Progression–Free Survival (PFS)
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Depth of Response

Deep responses^1,2*

In CARTITUDE-4 at 15.9 months

85% overall response rate was achieved with CARVYKTI^®, and 81% of patients achieved a deep response^1,2*

Overall response rate

Deep response is defined as ≥VGPR

CARTITUDE-4 depth of response for CARVYKTI® intent-to-treat population, graph

Percentages rounded to nearest whole number and may not add up due to rounding.

CI=confidence interval; CR=complete response; DPd=daratumumab, pomalidomide, and dexamethasone; ORR=overall response rate; PR=partial response; PVd=pomalidomide, bortezomib, and dexamethasone; sCR=stringent complete response; VGPR=very good partial response.

*Median follow-up was 15.9 months in the Intent-to-Treat Analysis Set.

^†Includes patients who achieved PR or better.

Overall Survival (OS)
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Duration of Response (DOR)

Durable responses

In CARTITUDE-4 at 15.9 months*

Median duration of response for CARVYKTI^® was not reached¹*

Median duration of response

CI=confidence interval; CR=complete response; DPd=daratumumab, pomalidomide, and dexamethasone; mDOR=median duration of response; NE=not estimable; PR=partial response; PVd=pomalidomide, bortezomib, and dexamethasone.

*Median follow-up was 15.9 months in the Intent-to-Treat Analysis Set.

^†Estimated mDOR.

Depth of Response
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Depth of Response

CARTITUDE-4 Primary Analysis

CARTITUDE-4: A pivotal phase 3 study in patients as early as first relapse^1,2

CARVYKTI^® was studied in patients with 1-3 prior lines of therapy^1,2