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Updated efficacy and safety analysis from the phase III CANDOR study

Jan 15, 2022
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On December 3, 2021, Saad Usmani and colleagues published the updated safety and efficacy analysis of the phase III CANDOR study (NCT03158688) in Lancet Oncology.1 This was a global, multicenter, randomized, open-label study comparing DKd (daratumumab, carfilzomib, and dexamethasone) with Kd (carfilzomib and dexamethasone) in patients with relapsed/refractory multiple myeloma. The U.S. Food and Drug Administration (FDA) and European Union have already approved this triplet combination for patients who have received 13 lines of treatment, which was based on the previous data analysis.1  

The current analysis was a preplanned interim analysis for overall survival; however, the data were not mature at the time of data cutoff (June 15, 2020).1 We summarize below the updated progression-free survival (PFS) data in the intention-to-treat population, with 11 months additional follow-up, as well as the updated safety analysis.

Results

For more information on baseline characteristics, dosing schedule, and initial response rates, read our summary here.

The updated median follow-up and median PFS, and other secondary endpoints, can be seen in Table 1. The difference in median PFS between the two cohorts remained significant (hazard ratio, 0.59; 95% confidence interval, 0.45–0.78; p < 0.0001). A similar PFS benefit was reported across prespecified subgroups.

Table 1. Updated efficacy results*

 

DKd (n = 312)

Kd (n = 154)

HR (95% CI)

Median follow-up (range), months

27.8 (25.6–29.5)

27.0 (13.2–28.6)

Median PFS (95% CI), months

28.6 (22.7–NE)

15.2 (11.1–19.9)

0.59 (0.45–0.78)

Median time to next treatment (95% CI),  months

NE (30.1–NE)

18.1 (13.6–25.0)

0.47 (0.35–0.63)

Median derived time to subsequent disease progression or death (95% CI), months

NE (NE–NE)

33.2 (33.2–NE)

0.73 (0.53–1.01)

CI, confidence interval; DKd, daratumumab, carfilzomib, dexamethasone; Kd, carfilzomib, dexamethasone; NE, not estimable; PFS, progression-free survival.
*Data from Usmani, et al.1


Therapies administered in the following line, after the study treatment, were similar between arms (mostly immunomodulatory drugs); however, anti-CD38-based therapies were more frequent in patients relapsing to Kd (18%) than to DKd (2%).

Grade ≥3 treatment-emergent adverse events occurred in 87% of patients in the KdD group compared with 76% in the Kd group. The most common Grade ≥3 treatment-emergent adverse events and serious adverse events can be seen in Table 2. A total of 11 patients discontinued carfilzomib due to cardiac failure, while pneumonia led to daratumumab discontinuation in four patients. This safety analysis was consistent with the primary analysis, and no new treatment-related deaths occurred.

Table 2. Most common Grade ≥3 TEAEs and serious AEs*

AE/TEAE, %

DKd (n = 308)

Kd (n = 153)

Grade ≥3 TEAEs

87

76

              Thrombocytopenia

25

16

              Hypertension

21

15

              Pneumonia

18

9

              Anemia

17

15

Serious AEs

63

50

AEs leading to death

9

5

              Septic shock

2

1

              Pneumonia

1

0

AEs leading to K-dose reduction

29

22

AEs leading to K discontinuation

26

22

AEs leading to study treatment discontinuation

28

25

AE, adverse event; DKd, daratumumab, carfilzomib, dexamethasone; K, carfilzomib; Kd, carfilzomib, dexamethasone; TEAE, treatment-emergent adverse event.
*Data from Usmani, et al.1

Conclusion

With a longer follow-up of 11 months (~27 months in total), DKd maintained a PFS benefit over Kd. Therefore, these results support the use of DKd as a standard treatment option for patients with relapsed/refractory multiple myeloma who have previously received 13 lines of therapy, including an immunomodulatory drug or a proteasome inhibitor (or both). However, overall survival results are needed to confirm a greater survival benefit with this triplet combination.

  1. Uzmani SZ, Quach H, Mateos MV, et al. Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): updated outcomes from a randomised, multicentre, open-label, phase 3 study. Lancet Oncol. 2022;23(1):65-76. DOI: 1016/S1470-2045(21)00579-9

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