Reason for request

Reevaluation

Key points

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?

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

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

  • either with lenalidomide (REVLIMID) combined with dexamethasone until disease progression, and the anti-CD38 monoclonal antibody daratumumab (DARZALEX) (DRd protocol),
  • or with bortezomib (VELCADE), melphalan and daratumumab (D-VMP protocol) for a fixed treatment duration.

Role of the medicinal product in the care pathway

Given the superiority of the protocol combining DARZALEX (daratumumab) with lenalidomide and dexamethasone (D-Rd protocol) until disease progression demonstrated in comparison with the Rd protocol, now in terms of overall survival, the D-Rd protocol is the treatment option to be favoured over the Rd protocol for the treatment of patients with previously untreated multiple myeloma who are ineligible for autologous stem cell transplant.

In the absence of direct comparative data, the role of the D-Rd protocol compared to the D-VMP protocol (combining bortezomib, melphalan and prednisone with daratumumab) available in the same indication, is not known. The choice should therefore be made taking into account the patient and disease characteristics, the safety profile of the protocols and the preferences of patients.

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), was observed in the study arm including DARZALEX (daratumumab), and is also reported in the literature. The benefit/risk ratio of the long-term continuation of DARZALEX (daratumumab) injections must therefore be reassessed regularly, before each administration, particularly in the event of an infectious episode.

Insofar as DARZALEX (daratumumab) has several marketing authorisations for the first and second-line treatment of myeloma, the Committee regrets that there are no ongoing studies capable of defining the optimal treatment sequence and encourages the implementation of a study of this type.


Clinical Benefit

Substantial

The Committee deems that the clinical benefit of DARZALEX (daratumumab) remains substantial in the indication: “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”.


Clinical Added Value

moderate

The Committee considers that DARZALEX (daratumumab) in combination with lenalidomide and dexamethasone (Rd protocol), provides a moderate clinical added value (CAV III) compared to the Rd protocol in the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant.

 


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