Matching-adjusted indirect comparison of efficacy outcomes for ciltacabtagene autoleucel in CARTITUDE-1 versus idecabtagene vicleucel in KarMMa for the treatment of patients with relapsed or refractory multiple myeloma

Figures & data

Table 1. Differences in baseline characteristics.

	Categories	Unadjusted comparison		Base case adjusted^a comparison	All variables adjusted^b comparison (sensitivity)
		KarMMa	CARTITUDE-1	CARTITUDE-1	CARTITUDE-1
		%	%	%	%
		N = 124	N = 97	N (ESS)=96 (52)	N (ESS)=96 (42)
All Variables
Base Case Variables
Refractory status	Non triple-class refractory	16	12	16	16
	Triple or quad refractory only^c	58	45	58	58
	Penta-refractory^d	26	42	26	26
Cytogenetic profile	High-risk^e	36	24	36	36
	Standard risk/ unknown	64	76	64	64
R-ISS stage	I	12^f	34^g	12	12
	II	71^f	59^g	71	71
	III	17^f	7^g	17	17
Presence of all plasmacytomas	No	60	80	60	60
	Yes	40^h	20	40	40
Number of prior LOTs	Median	6	6	5	6
Years since MM diagnosis	Median	7	6	6	7
Age (years)	Median	61	61	62	61
Prior stem cell transplant	No	6^i	10	8	6
	Yes	94^i	90	92	94
ECOG status	0	44	40	33	44
	1	56	60	67	56
Sex	Female	42	41	42	42
	Male	58	59	58	58

^aPatients from CARTITUDE-1 who satisfied KarMMa’s eligibility criteria were adjusted for refractory status, cytogenetic profile, R-ISS stage, and all plasmacytomas in the base case analysis.

^bPatients from CARTITUDE-1 who satisfied KarMMa’s eligibility criteria were adjusted for refractory status, cytogenetic profile, R-ISS stage, all plasmacytomas, number of prior LOTs, years since MM diagnosis, age, prior stem cell transplant, ECOG status, and sex in the sensitivity analysis.

^cRefractory to two IMiDs and one PI; or two PIs and one IMiD; or two IMiDs and two PIs.

^dRefractory to at least two IMiDs, two PIs, and an anti-CD38 MoAB.

^eHigh-risk defined as at least one of del17p, t(4;14), or t(14;16).

^fPercentages are out of 121 (3 patients from KarMMa with missing R-ISS were excluded).

^gIn CARTITUDE-1, R-ISS was derived, rather than prospectively collected.

^hDefined as “paraskeletal soft-tissue masses, soft-tissue masses spreading outside the bone marrow, or both”.

ⁱAutologous stem cell transplant.

Abbreviations. ECOG, Eastern Cooperative Oncology Group; ESS, effective sample size; IMiD, immunomodulatory drug; LOTs, lines of therapy; MM, multiple myeloma; MoAB, monoclonal antibody; PI, proteasome inhibitor; R-ISS, revised International Staging System.

Source: The baseline characteristics for CARTITUDE-1 were derived using individual patient data from the February 2021 data cut. KarMMa baseline patient characteristics from 2021 NEJM publication by Munshi et al. [10].

Table 2. Response rates and comparative efficacy for cilta-cel versus ide-cel.

	Unadjusted comparison			Base case adjusted^a comparison			All variables adjusted^b comparison (sensitivity)
	Observed response rate		OR^c (95%CI), p-value	Adjusted response rate	OR^c (95%CI), p-value	Relative risk^d	Adjusted response rate	OR^c (95%CI), p-value	Relative risk^d
	Cilta-cel (%)	Ide-cel (%)	Cilta-cel vs Ide-cel (%)	Cilta-cel (%)	Cilta-cel vs Ide-cel	Cilta-cel vs Ide-cel	Cilta-cel (%)	Cilta-cel vs Ide-cel	Cilta-cel vs Ide-cel
Overall Response Rate	97.9	74.2	16.52 (3.85, 70.93), p = .0002	99.6	94.93 (21.86, 412.25), p < .0001	1.34	99.5	70.53 (12.23, 406.82), p < .0001	1.34
Complete Response or Better Rate	80.4	33.1	8.31 (4.45, 15.54), p < .0001	73.0	5.49 (2.47, 12.21), p < .0001	2.21	67.4	4.18 (1.86, 9.43), p = .0006.	2.04

^aPatients from CARTITUDE-1 who satisfied KarMMa’s eligibility criteria were adjusted for refractory status, cytogenetic profile, revised International Staging System stage, and all plasmacytomas in the base case analysis.

^bPatients from CARTITUDE-1 who satisfied KarMMa’s eligibility criteria were adjusted for refractory status, cytogenetic profile, revised International Staging System stage, all plasmacytomas, number of prior lines of therapy, years since multiple myeloma diagnosis, age, prior stem cell transplant, Eastern Cooperative Oncology Group status, and sex in the sensitivity analysis.

^cOdds ratios (ORs) >1 are in favor of cilta-cel versus ide-cel.

^dRelative risks are equal to the ratio of the adjusted response rates for cilta-cel versus the observed response rates for ide-cel.

Abbreviations. CI, confidence interval; ESS, effective sample size; OR, odds ratio.

Table 3. Estimated medians and comparative efficacy for cilta-cel versus ide-cel.

	Unadjusted comparison			Base case adjusted^a comparison		All variables adjusted^b comparison (sensitivity)
	Median, months (95% CI)		HR^c (95% CI), p-value	Median, months (95% CI)	HR^c (95% CI), p-value	Median, months (95% CI)	HR^c (95% CI), p-value
	Ide-cel	Cilta-cel	Cilta-cel vs Ide-cel	Cilta-cel	Cilta-cel vs Ide-cel	Cilta-cel	Cilta-cel vs Ide-cel
Duration of Response^d	11.1 (9.1, 11.3)	21.8 (21.8, NR)^e	0.33 (0.21, 0.52), p < .0001	21.8 (12.9, NR)^e	0.50 (0.29, 0.87), p = .0137	15.9 (12.9, NR)^e	0.58 (0.33, 1.02), p = 0.0600
Progression-free Survival	9.2 (6.0, 12.1)	22.8 (22.8, NR)^e	0.26 (0.17, 0.40), p < .0001	22.8 (14.6, NR)^e	0.37 (0.22, 0.62), p = .0002	16.8 (1.0, NR)^e	0.43 (0.25, 0.73), p = .0016
Overall Survival^f	19.5 (18.9, NR)	NR (23.6, NR)	0.39 (0.23, 0.66), p = .0004	NR (22.8, NR)	0.55 (0.29, 1.05), p = .0702	NR (22.8, NR)	0.62 (0.31, 1.23), p = .1680

^aPatients from CARTITUDE-1 who satisfied KarMMa’s eligibility criteria were adjusted for refractory status, cytogenetic profile, revised International Staging System stage, and all plasmacytomas in the base case analysis.

^bPatients from CARTITUDE-1 who satisfied KarMMa’s eligibility criteria were adjusted for refractory status, cytogenetic profile, revised International Staging System stage, all plasmacytomas, number of prior lines of therapy, years since multiple myeloma diagnosis, age, prior stem cell transplant, Eastern Cooperative Oncology Group status, and sex in the sensitivity analysis.

^cHazard ratios (HRs) <1 are in favor of cilta-cel.

^dFor KarMMa, estimates were calculated using the number of responders (N = 92).

^eMedians should be interpreted with caution, as reached when few patients were still at risk and may be an underestimate.

^fFor KarMMa, estimates were calculated using publicly available data, which excluded one patient who received a non-confirming product that did not meet product release specifications for ide-cel (N = 123).

Abbreviations: CI, confidence interval; HR, hazard ratio; NR, not reached.

Figure 1. Observed (unadjusted) and adjusted (base case) Kaplan–Meier plots of a duration of response. Note. Base case results adjusted for refractory status, cytogenetic profile, revised International Staging System stage, and all plasmacytomas. Abbreviations: ESS, effective sample size.

Figure 2. Observed (unadjusted) and adjusted (base case) Kaplan–Meier plots of progression-free survival. Note. Base case results adjusted for refractory status, cytogenetic profile, revised International Staging System stage, and all plasmacytomas. Abbreviations: ESS, effective sample size.

Figure 3. Observed (unadjusted) and adjusted (base case) Kaplan–Meier plots of overall survival. Note. Base case results adjusted for refractory status, cytogenetic profile, revised International Staging System stage, and all plasmacytomas. Abbreviations: ESS, effective sample size.

Munshi NC, Anderson LD, Jr Shah N, et al. Idecabtagene vicleucel in relapsed and refractory multiple myeloma. N Engl J Med. 2021;384(8):705–716.

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Data availability statement

Requests for access to the CARTITUDE-1 trial study data may be submitted through the Yale Open Data Access (YODA) Project site at http://yoda.yale.edu. The data sharing policy of Janssen Pharmaceutical Companies is available at https://www.janssen.com/clinical-trials/transparency. For KarMMa study, a data sharing statement is available with the full text of the primary publication at NEJM.org¹⁰.