SARCLISA (isatuximab)

Key points

Favourable opinion for reimbursement in combination with pomalidomide and dexamethasone, for the treatment of adult patients with relapsed and refractory multiple myeloma (MM) who have received at least two prior therapies including lenalidomide and a proteasome inhibitor (PI) and have demonstrated disease progression on the last therapy.

What therapeutic improvement?

Therapeutic improvement compared to the pomalidomide plus dexamethasone combination.

Role in the care pathway?

From the second relapse, in patients who have already been treated with VELCADE (bortezomib) and REVLIMID (lenalidomide), IMNOVID (pomalidomide) has an MA in combination with dexamethasone. However, given the evolution of the care pathway in multiple myeloma, with new medicinal products having been added to the therapeutic arsenal in earlier treatment lines, the role of IMNOVID (pomalidomide) in combination with dexamethasone has become more limited. In addition, earlier use of IMNOVID (pomalidomide) from the second line of treatment in combination with bortezomib and dexamethasone is likely to substantially reduce the benefit of pomalidomide-dexamethasone dual therapy in subsequent treatment lines. FARYDAK (panobinostat) combined with bortezomib and dexamethasone, represents a last-resort treatment option for patients with relapsed and/or refractory myeloma, having previously received two lines of treatment, including bortezomib and an immunomodulator. Finally, DARZALEX (daratumumab) is also an option in patients with relapsed and refractory multiple myeloma, whose prior therapy included a proteasome inhibitor and an immunomodulatory agent; however, its earlier use (currently possible from first-line therapy) in the context of combination with a proteasome inhibitor (PI) or an IMiD, substantially reduces the benefit of this monotherapy in subsequent treatment lines.

Role of the medicinal product in the care pathway

Given the demonstrated superiority of the Isa-Pd protocol combining SARCLISA (isatuximab) with IMNOVID (pomalidomide) plus dexamethasone (Pd) until progression compared to the Pd combination in terms of progression-free survival and pending the final results in terms of overall survival, the Isa-Pd combination is the treatment option to be favoured over the Pd combination in adult patients with relapsed and refractory multiple myeloma (MM) who have received at least two prior therapies including lenalidomide and a proteasome inhibitor (PI) and have demonstrated disease progression on the last therapy.

However, the Committee regrets that the available study does not enable definition of the optimal treatment sequence between the use of a triple combination of an anti-CD38 antibody along with pomalidomide and dexamethasone from the outset and the sequential use of pomalidomide plus dexamethasone and an anti-CD38 antibody from the second relapse. In fact, DARZALEX (daratumumab), as monotherapy, is still an option in patients having received an IP and an immunomodulatory agent.

Given the similar mechanism of action, targeting the CD38 receptor, and the non-inclusion in the ICARIA-MM study of patients refractory to an anti-CD38 antibody received in a prior treatment line, the Committee does not recommend the use of SARCLISA (isatuximab) in patients refractory to an anti-CD38 antibody. In addition, no robust data supports the value of re-using SARCLISA (isatuximab) in patients previously treated with an anti-CD38 antibody but not refractory to an anti-CD38 antibody.

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 SARCLISA (isatuximab), as it did for DARZALEX (daratumumab). An excess of sometimes severe infectious episodes, particularly respiratory tract infection (including with opportunistic microorganisms), was observed in the study arm receiving SARCLISA (isatuximab). The benefit/risk ratio of the long-term continuation of SARCLISA (isatuximab) injections must also be reassessed regularly, particularly in the event of an infectious episode.

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