Carfilzomib, daratumumab, and dexamethasone (KdD) vs. lenalidomide-sparing pomalidomide-containing triplet regimens for relapsed/refractory multiple myeloma: an indirect treatment comparison

Figures & data

Table 1. Baseline characteristics.

	CANDOR	OPTIMISMM	APOLLO
Data source	CANDOR data (June 2021 data cut)	Richardson et al. Lancet Oncol. 2019	Sonneveld et al. ASH 2021
Intervention and comparator	ITT: KdD (n = 312) vs. Kd (n = 154)	PVd (n = 281) vs. Vd (n = 278)	DPd (n = 151) vs. Pd (n = 153)
	Lenalidomide-exposed: KdD (n = 123) vs. Kd (n = 74)
Comparison of KdD, PVd, and DPd populations (lenalidomide-exposed patients)
Age ≥65 years, ≥75 years, %	52.0%, 6.5%	56.2% (>65), 16.4% (>75)	58.3%, 16.6%
ECOG PS 0, 1, 2	44.7%, 52.0%, 3.3%	53.0%, 43.1%, 3.9%	60.3%, 35.8%, 4.0%
ISS disease stage, %	50.4%, 29.3%, 19.5% (missing data: 1 patient)	53.0%, 30.2%, 16.7%	45.0%, 33.1%, 21.9%
Median time from diagnosis	3.5 years	4.0 years	4.4 years
≥2 prior therapies, %	78.0%	60.5%	89.4%
Lenalidomide-exposed, %	100%	100%	100%
Lenalidomide-refractory, %	80.5%	71.2%	79.5%
Bortezomib-exposed, %	95.9% (PI)	75.4% (PI)	100% (PI)
	94.3% (bortezomib)	71.5% (bortezomib)	–
Bortezomib-refractory, %	39.0% (PI)	–	47.0% (PI-refractory)
	31.7% (bortezomib)	8.5% (bortezomib)	–
Prior ASCT, %	61.8%	57.3%	59.6%
Refractory to last prior therapy	75.6%	69.8%	80.8%
Comparison of KdD, PVd, and DPd outcomes (lenalidomide-exposed patients)
Median follow-up, months	38.5	15.9	30.7
Median PFS, months	KdD: 27.0, Kd: 11.1	PVd: 11.2, Vd: 7.1	DPd: 12.1, Pd: 7.0
HR (95% CI)	0.53 (0.36, 0.78)	0.61 (0.49, 0.77)	0.63 (0.48, 0.83)

ASCT: autologous stem cell transplantation; CI: confidence interval; DPd: daratumumab plus pomalidomide and dexamethasone; ECOG: Eastern Cooperative Oncology Group; HR: hazard ratio; ISS: International Staging System; ITT: intention to treat; Kd: carfilzomib and dexamethasone; KdD: carfilzomib, dexamethasone, and daratumumab; Pd: pomalidomide and dexamethasone; PFS: progression-free survival; PI: proteasome inhibitor; PS: performance status; PVd: pomalidomide, bortezomib, and dexamethasone; Vd: bortezomib and dexamethasone.

Figure 1. Unadjusted progression-free survival Kaplan-Meier curves among lenalidomide-exposed patients. DPd: daratumumab plus pomalidomide and dexamethasone; ITT: intention to treat; KdD: carfilzomib, dexamethasone, and daratumumab; PFS, progression-free survival; PVd, pomalidomide, bortezomib, and dexamethasone.

Figure 2. Landmark analyses at 6-, 12-, 24- and 36-month timepoints and progression-free survival Kaplan-Meier curves for the matched population for KdD (lenalidomide-exposed subgroup) and PVd (full trial population). HR: hazard ratio; ITT: intention to treat; KdD: carfilzomib, dexamethasone, and daratumumab; PFS: progression-free survival; PVd: pomalidomide, bortezomib, and dexamethasone.

Table 2. Summary results for base-case and scenario matching-adjusted indirect treatment comparison analyses.

Description of analysis	Effective sample size	HR (95% CI)
KdD vs. PVd: lenalidomide exposed
Base case	32.3	0.60 (0.37, 0.88)
Exclude prior bortezomib from matching algorithm	58.0	0.61 (0.40, 0.88)
Exclude refractoriness to lenalidomide from matching algorithm	34.7	0.59 (0.38, 0.88)
Exclude prior bortezomib and refractoriness to lenalidomide from matching algorithm	58.9	0.61 (0.40, 0.88)
Include refractoriness to bortezomib in the matching algorithm	28.3	0.66 (0.44, 1.01)
Include risk status in matching algorithm*	23.9	0.59 (0.38, 0.93)
Include age ≥75 years only (instead of age ≥65 and ≥75 years) in matching algorithm	32.3	0.57 (0.36, 0.92)
Exclude ECOG PS in matching algorithm	32.5	0.59 (0.37, 0.94)
Exclude number of prior lines of treatment in matching algorithm	35.7	0.65 (0.41, 1.03)
Include refractory to bortezomib in the matching algorithm	28.3	0.66 (0.44, 1.01)
KdD vs. DPd: lenalidomide exposed
Base case	68.1	0.77 (0.50, 1.08)
Exclude refractoriness to last prior regimen in matching algorithm	68.4	0.77 (0.51, 1.07)
Exclude ECOG PS in matching algorithm	70.8	0.77 (0.50, 1.08)
Exclude prior SCT in matching algorithm	68.5	0.75 (0.50, 1.07)
Exclude refractoriness to last prior regimen, ECOG status, prior SCT in the matching algorithm	71.4	0.75 (0.50, 1.08)
Include risk status in matching algorithm*	47.8	0.71 (0.44, 1.03)
Include age ≥75 years only (instead of age ≥65 and ≥75 years) in matching algorithm	68.3	0.76 (0.53, 1.07)
Exclude number of prior lines of treatment in matching algorithm	69.5	0.75 (0.53, 1.06)
Exclude PI refractory to bortezomib in the matching algorithm	69.1	0.78 (0.56, 1.09)

OPTIMISMM: In the base-case comparison, matching was performed on the following variables: time from diagnosis, ISS, age, number of prior lines of treatment, ECOG status, prior SCT, refractory to last prior treatment, refractory to lenalidomide, refractory to PI; 95% CIs were determined by bootstrapping drawing samples from both the CANDOR data and the replicated OPTIMISMM data.

APOLLO: In the base-case comparison, matching was performed on the following variables: time from diagnosis, ISS, number of prior lines of treatment, age, creatinine clearance, ECOG status, prior SCT, prior bortezomib, refractory to last prior treatment, refractory to lenalidomide; 95% CIs were determined by bootstrapping drawing samples from both the CANDOR data and the replicated APOLLO data.

CI: confidence interval; DPd: daratumumab plus pomalidomide and dexamethasone; ECOG: Eastern Cooperative Oncology Group; HR: hazard ratio; ISS: International Staging System; KdD: carfilzomib, dexamethasone, and daratumumab; NA: not applicable; Pd: pomalidomide and dexamethasone; PFS: progression-free survival; PS: performance status; SCT: stem cell transplantation.

Figure 3. Landmark analyses at 6-, 12-, 24- and 36-month timepoints and progression-free survival Kaplan-Meier curves for the matched population for KdD (lenalidomide-exposed subgroup) and PVd (full trial population). DPd: daratumumab plus pomalidomide and dexamethasone; HR: hazard ratio; ITT: intention to treat; KdD: carfilzomib, dexamethasone, and daratumumab; PFS: progression-free survival.

Data availability statement

Qualified researchers may request de-identified data from Amgen clinical studies. Complete details are available at the following: http://www.amgen.com/datasharing.