DARZALEX

New indication.

Favourable opinion for reimbursement in combination with lenalidomide and dexamethasone for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant.

What therapeutic improvement?

Therapeutic improvement compared to the Rd protocol combining lenalidomide and dexamethasone.

Role in the care pathway?

The current classification for myeloma, developed on the basis of International Myeloma Working Group criteria, divides patients into two categories: asymptomatic patients for whom simple monitoring is generally recommended, and symptomatic patients requiring appropriate management adapted to age and comorbidities.

In symptomatic patients, first-line treatment is dependent on whether the subject is eligible or not for intensive chemotherapy combined with autologous peripheral blood stem cell transplantation.

When patients are not eligible for a transplant (in particular, due to their age, their comorbidities and/or their general condition), the therapeutic strategy is based on chemotherapy:

• either with bortezomib (VELCADE), melphalan and prednisone (VMP protocol) for a fixed duration, potentially combined with the anti-CD38 monoclonal antibody DARZALEX (daratumumab),
• or with lenalidomide (REVLIMID) combined with low doses of dexamethasone (Rd protocol) until disease progression.

Role of the medicinal product in the care pathway

Given the superiority of the DARZALEX (daratumumab) protocol, administered in combination with lenalidomide and dexamethasone (Rd protocol) until disease progression, demonstrated in comparison with the Rd protocol, the D-Rd protocol is a first-line treatment for patients with previously untreated multiple myeloma who are ineligible for autologous stem cell transplant.

In patients ineligible for autologous stem cell transplant, two different protocols based on daratumumab have an MA: D-VMP (combination with bortezomib, melphalan and prednisone) and now D-Rd. To date, only the D-VMP protocol has demonstrated a benefit in terms of overall survival compared to the VMP protocol. No comparative data are available or scheduled to assess these two protocols based on daratumumab. The choice should therefore be made taking into account the level of evidence of the demonstration, the profile and preferences of patients, the characteristics of the disease and its potential complications and the safety of the protocols.

The Committee wishes to draw the attention of prescribers to the need for specific vigilance with respect to the risk of immune deficiency induced by the long-term administration of DARZALEX (daratumumab). An excess of sometimes severe infectious episodes, particularly respiratory tract infection (including with opportunistic microorganisms), is observed in the study arm including DARZALEX (daratumumab), and is also reported in the literature and according to expert opinion.