DARZALEX (daratumumab) - Multiple myeloma

The clinical benefit of DARZALEX 1,800 mg (daratumumab) solution for injection in combination with bortezomib, lenalidomide and dexamethasone (D-VRd protocol), is low in the indication: “in combination with bortezomib, lenalidomide and dexamethasone for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant”.

Considering:

• evidence of the superiority of the addition of DARZALEX (daratumumab) to the VRd protocol in terms of minimal residual disease negativity (OR = 2.07; 95% CI = [1.38; 3.10]) and progression-free survival (HR = 0.61, 95% CI = [0.42; 0.90]); however, it should be noted that the comparator, (VRd protocol) was accepted at the time of implementation of the CEPHEUS study but was no longer a reference treatment on the date of the assessment, this having been the case since the marketing authorisation was issued for DARZALEX (daratumumab) in the context of the D-VMP (31/08/2018) and D-Rd (19/11/2019) protocols;
• uncertainties with respect the transposability of the results of the CEPHEUS study to the indication concerned by the application (in patients ineligible for autologous stem cell transplant): this study having included patients eligible for autologous stem cell transplant but who chose to delay it (26.8% of patients included in the CEPHEUS study);
• uncertainties with respect to the surrogacy for overall survival of the primary endpoint of the CEPHEUS study (minimal residual disease negativity);
• the lack of evidence of a benefit in terms of overall survival;
• the absence of robust quality of life data;
• the safety profile of the experimental arm marked by additional haematological toxicity (D-VRd: 82.7%; VRd: 64.6%) and risk of infection (D-VRd: 91.9%; VRd: 85.6%), as well as an increase in deaths related to an adverse event (D-VRd: 16.8%; VRd: 10.8%);
• and the impossibility of positioning the D-VRd protocol compared to the D-Rd, D-VMP and Isa-VRd protocols, in the absence of sufficiently robust direct or indirect comparative data;

the Committee deems that DARZALEX 1,800 mg (daratumumab) solution for injection in combination with bortezomib, lenalidomide and dexamethasone (D-VRd protocol) provides no clinical added value (CAV V) in the current care pathway for the first-line treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant.