EMPLICITI (elotuzumab) - Myélome multiple

Key points

Approval of reimbursement in association with lenalidomide and dexamethasone for the treatment of multiple myeloma in adult patients having received at least one previous treatment.

Therapeutic improvement?

No therapeutic improvement with respect to the lenalidomide and dexamethasone association.

Role in therapeutic strategy?

For symptomatic patients, the first treatment is dependent on whether the patient is eligible for intensive chemotherapy associated with autologous peripheral blood stem cell transplantation (APBSCT). DARZALEX (daratumumab) has also been included in the therapeutic strategy as a first treatment, regardless of APBSCT status, in association with regimens including an immunomodulatory drug IMID (thalidomide or REVLIMID (lenalidomide)) and/or a proteasome inhibitor PI [VELCADE (bortezomib)] and/or melphalan.

In the event of relapse or progression after the first treatment, the therapeutic decision is dependent on age, previous treatments, duration of the first remission, and the circumstances of the relapse, PBC availability, the patient’s general state of health and comorbidities. The treatments are based on a bitherapy or tritherapy associating pomalidomide (IMNOVID), daratumumab (DARZALEX), ixazomib (NINLARO) or carfilzomib (KYPROLIS), isatuximab (SARCLISA) with bortezomib (VELCADE) or with lenalidomide (REVLIMID) and/or with dexamethasone.

From the second relapse, for patients previously treated with VELCADE (bortezomib) and REVLIMID (lenalidomide), IMNOVID (pomalidomide) has been granted a marketing authorisation in association with dexamethasone. Nevertheless due to updates to the therapeutic strategy for multiple myeloma with new medicinal products joining the therapeutic arsenal at an earlier stage, the role of IMNOVID (pomalidomide) in association with dexamethasone has become restricted. Furthermore, the earlier use of IMNOVID (pomalidomide) in the context of an association with bortezomib and dexamethasone should considerably reduce the benefit of pomalidomide/dexamethasone bitherapy in subsequent treatments. FARYDAK (panobinostat) in association with bortezomib and dexamethasone is another therapeutic option as a last-resort treatment, for relapsed and/or refractory myeloma having already received two previous two lines of treatment including bortezomib and an IMID. DARZALEX (daratumumab) is also an option for relapsed and refractory multiple myeloma patients, whose previous treatments included a PI and an IMID; nevertheless, its earlier use (currently possible as first treatment) in the context of an association with a PI or with an IMID, considerably reduces the benefit of this monotherapy in subsequent treatments. SARCLISA (isatuximab) has been included in the therapeutic strategy in association with pomalidomide and with dexamethasone for patients having received at least two previous treatments including lenalidomide and a PI.

Beyond that, for heavily pre-treated patients at a very advanced phase, BLENREP (belantamab mafodotin) has been granted a marketing authorisation for the treatment of adult multiple myeloma patients, having received at least 4 previous treatments and whose disease is refractory to at least an proteasome inhibitor, an immunomodulatory drug and an anti-CD38 monoclonal antibody, and whose disease progressed during the most recent treatment. The Transparency Committee deemed it to be a secondary treatment, when all treatment options have been exhausted, following a multidisciplinary review meeting opinion.

Recently, ABECMA (idecabtagene vicleucel) was also granted a marketing authorisation for relapsed and refractory multiple myeloma patients, who have received at least three previous treatments, including an immunomodulatory drug, a proteasome inhibitor, and an anti-CD38 antibody, and whose disease progressed during the most recent treatment. The Transparency Committee deemed that it was fourth-line or subsequent treatment, and that it was not possible to specify its role in relation to BLENREP (belantamab mafodotin) on account of the lack of methodologically robust comparative data.

Recently, CARVYKTI (ciltacabtagene autoleucel) was granted a marketing authorisation for the treatment of relapsed and refractory adult multiple myeloma patients, having received at least three

previous treatments. TECVAYLI (teclistamab) has been granted a conditional marketing authorisation for this indication.

Role of EMPLICITI (elotuzumab) in the therapeutic strategy:

The marketing authorisation of EMPLICITI (elotuzumab) in association with lenalidomide and dexamethasone (E-Rd) places the E-Rd association as a treatment indicated for multiple myeloma, in adult patients who have received at least one previous treatment.

Nevertheless, the Committee would like to point out the late filing of the reimbursement application for EMPLICITI (elotuzumab) which was granted a marketing authorisation in 2016, and the update of the treatment strategy of multiple myeloma as a second-line or subsequent treatment. Consequently, the transposability of the findings of the ELOQUENT-2 study to the current strategy is not guaranteed and the role of EMPLICITI (elotuzumab) is difficult to determine. The Committee also points out the lack of availability of data on the efficacy of the E-Rd association after DARZALEX (daratumumab) treatment, now recommended from the first line of treatment, regardless of eligibility status in respect of autologous peripheral blood stem cell transplantation.

Finally, the role of the E-Rd regimen, versus the regimens currently recommended from the second line, in particular bitherapies or tritherapies associating pomalidomide (IMNOVID), daratumumab (DARZALEX), ixazomib (NINLARO) or carfilzomib (KYPROLIS), isatuximab (SARCLISA) with bortezomib (VELCADE) or with lenalidomide (REVLIMID) and/or with dexamethasone, is not known. The choice between the different therapeutic options must take account particularly of the refractory or non-refractory status to lenalidomide and previous exposure to daratumumab as a first-line treatment, the patient’s characteristics (age, comorbidities), as well as the level of evidence and the toxicity profile.