A new subcutaneous formulation of isatuximab for the treatment of multiple myeloma

In this video, Dr Fredrik Schjesvold, director of the Oslo myeloma center at the univeristy hospital of Oslo discusses two studies evaluating a subcutaneous (SC) formulation of the anti-CD38 monoclonal antibody isatuximab in patients with multiple myeloma (MM)

Based on the results of the phase III ICARIA-MM study, intravenous (IV) isatuximab in combination with pomalidomide and dexamethasone (Isa-Pd) is EMA approved for the treatment of patients with relapsed/refractory MM (RRMM). However, the classical IV administration of isatuximab gives it a disadvantage over the other CD38 monoclonal antibody daratumumab which is already available in a SC form. Previously, a Phase 1b study demonstrated the safety and efficacy of Pd in combination with a SC administration of isatuximab using an on-body delivery system (OBDS). Main advantages of SC isatuximab delivered through this OBDS include a shorter duration of administration, the ability to use isatuximab in a fixed dose, and the smaller administration volume. In the phase III IRAKLIA study, isatuximab SC OBDS was compared to isatuximab IV both in combination with Pd in patients with RRMM.¹

The IRAKLIA study included a total of 531 patients with a median age of 66 years and a median of 2 prior treatment lines. The study demonstrated a similar response rate with both isatuximab formulations and showed a higher drug exposure to isatuximab with the SC OBDS administration. Also in terms of adverse events (AEs) the study did not reveal any difference between both treatment arms. An important exception to this, concerned the markedly lower rate of infusion related reactions with the SC isatuximab formulation. In addition to this, the study revealed a much higher patient satisfaction with SC isatuximab compared to the classical IV formulation.¹

A second abstract discussed by Dr Schjesvold concerned a poster with updated results of the phase II IZALCO study.² This trial evaluated the efficacy, safety, pharmacokinetics, and patient preference of SC isatuximab administered as a manual injection or via the OBDS system. In this trial, isatuximab was combined with carfilzomib and dexamethasone (Kd).² While the efficacy and safety outcomes in this trial were similar for the manual and OBDS system, three quarters of patients indicated to have a preference for the OBDS system. The pharmacokinetic exposure to isatuximab was comparable with both modes of administration.²

In concluison, the IRAKLIA and IZALCO studies support the adminstration of SC isatuximab using an on-body device. This mode of administration leads to similar effiacy and safety outcomes, but is clearly preferred by patients.