CANDOR trial design: Investigating KdD versus Kd in relapsed/refractory multiple myeloma

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Published: 13 Jun 2020
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Prof Katja Weisel - University Medical Center Hamburg-Eppendorf, Hamburg, Germany

Prof Katja Weisel speaks to ecancer about the phase III CANDOR study that she presented at the virtual EHA 2020 conference.

She details the design of the study which looked at the combination of carfilzomib, dexamethasone and daratumumab (KdD) versus carfilzomib and dexamethasone (Kd) in patients with relapsed or refractory multiple myeloma (RRMM).

Prof Weisel also explains patients were grouped according to categories based on prior lines of therapy and types of therapy.

ecancer's filming has been kindly supported by Amgen through the ecancer Global Foundation. ecancer is editorially independent and there is no influence over content.
 

The CANDOR study, basically from the study design, was a 2-to-1 randomised trial. Patients were included when they were adult and had first to third relapse of multiple myeloma and who were eligible and were then randomised between carfilzomib, daratumumab and dexamethasone, the KdD regimen, versus carfilzomib and dexamethasone, the Kd regimen.

The hazard ratio for PFS was comparable between patients with one prior therapy and those with two or more prior therapies. For the analysis by previous lenalidomide treatment patients were grouped into categories of lenalidomide exposed or naïve and lenalidomide refractory or non-refractory and the hazard ratio for PFS was comparable between the lenalidomide exposed and refractory subgroups but the observed PFS difference was lower in the lenalidomide naïve subgroup. For the analysis by previous bortezomib treatment patients were grouped into categories of bortezomib exposed or naïve and bortezomib refractory or non-refractory and the hazard ratio for PFS was comparable across the bortezomib exposed, naïve and non-refractory subgroups but the observed PFS difference was lower in the bortezomib refractory subgroup. This overall showed that the benefit-risk profile of KdD compared with Kd was generally consistent across subgroups regardless of the number of prior lines and prior treatment with lenalidomide or bortezomib.

The CANDOR trial is a phase III randomised trial for relapsed and refractory multiple myeloma patients with one to three prior lines investigating the triplet treatment of daratumumab in combination with carfilzomib and dexamethasone in a 2-to-1 randomisation compared to the standard treatment doublet of carfilzomib and dexamethasone. The initial results were presented at last year’s ASH meeting and showed a clear superiority regarding the primary endpoint, regarding progression free survival, in favour of the triplet combination of daratumumab in combination with carfilzomib and dexamethasone.

Here we now presented subgroup analysis by prior lines of therapy and pre-exposure to lenalidomide or bortezomib. Overall we could say that the PFS benefit for carfilzomib in combination with daratumumab and dexamethasone, for the triplet combination, was overall through every analysed subgroup and it was regardless of number of prior lines, one prior line versus two or three prior lines, and regardless of pre-exposure to bortezomib or to lenalidomide.
The PFS difference was slightly lower in the bortezomib refractory or pre-exposed or in the lenalidomide pre-exposed subgroup compared to the naïve subgroups. But the statistical significance in favour for the triplet combination was always proven.

So, in conclusion, those analyses again confirmed the clear superiority of the triplet combination of dara-Kd over the doublet with Kd alone. This will be again confirmed in the late breaking session of this year’s ASCO with another trial investigating monoclonal anti-CD38 antibody treatment in combination with carfilzomib dexamethasone, here with the monoclonal anti-CD38 antibody isatuximab, and these data will be presented in the late breaking session on Saturday by Philippe Moreau.

Overall in regards that nearly any myeloma patient now will receive lenalidomide in first line treatment when we think about the approval of daratumumab len-dex for transplant non-eligible and daratumumab VTd in transplant eligible patients. We have also the lenalidomide maintenance as standard of care after autologous stem cell transplantation. We have an urgent and unmet need for lenalidomide free relapse regimens which are effective. With those triplet combinations we are waiting we have then a definite new standard of care. How the impact of a previous daratumumab treatment will be on those regimens, again, using daratumumab we have so far no data.