Evaluating the effectiveness and safety of adding isatuximab to lenalidomide, bortezomib, and dexamethasone combination for patients with newly diagnosed transplantation-eligible multiple myeloma.

This study evaluated the effectiveness and safety of adding isatuximab (Sarclisa) to lenalidomide (Revlimid), bortezomib (Velcade), and dexamethasone (Decadron) combination as induction therapy for patients with newly diagnosed transplantation-eligible multiple myeloma (MM). The data showed that the addition of isatuximab to lenalidomide, bortezomib, and dexamethasone was effective with manageable side effects for these patients.

MM is a type of cancer that comes from blood cells called plasma cells. The current recommended treatment for newly diagnosed MM involves first-line treatment with lenalidomide in combination with dexamethasone and bortezomib followed by autologous stem cell transplantation (ASCT) and maintenance therapy. ASCT involves transplanting healthy stem cells from the same patient.

Lenalidomide is an immunotherapy drug that boosts the body’s immune system to help it attack cancer cells. Bortezomib is a proteasome inhibitor. Proteasomes are large molecules present in all body cells. It blocks the action of proteasomes, therefore preventing cancer cells from growing and multiplying. Dexamethasone is a corticosteroid that reduces inflammation and side effects to therapy. Isatuximab is an immunotherapy drug that has been approved for the treatment of relapsed or refractory MM. However, the effectiveness and safety of adding isatuximab to lenalidomide, bortezomib, and dexamethasone combination as induction therapy for patients with newly diagnosed transplantation-MM are still unknown.

This study involved 660 patients with newly diagnosed transplant-eligible MM. Patients were randomly assigned into 2 groups. Group 1 included 331 patients who received isatuximab plus lenalidomide, bortezomib, and dexamethasone combination. Group 2 included 329 patients who received lenalidomide, bortezomib, and dexamethasone combination alone. The average follow-up time was 125 days.

50% of patients in group 1 achieved negative minimal residual disease (MRD; no cancer cells that remain after treatment) compared to 36% in group 2. This difference was considered statistically significant. Group 1 was 82% more likely to achieve negative MRD than group 2. 

A complete response (complete disappearance of cancer cells) was achieved by 24% of patients in group 1 compared to 22% of those in group 2. This difference was not statistically significant. A very good partial response (disappearance of more than 90% of cancer cells) was achieved by 77% of patients in group 1 compared to 61% of those in group 2. This difference was considered statistically significant. Patients in group 1 were 2.13 times more likely to achieve a very good partial response or better compared to group 2. 

The rate of serious side effects was similar between the two groups (63% in group 1 and 61% in group 2). The most common side effects were low white blood cell counts and infections. 

This study concluded that the addition of isatuximab to lenalidomide, bortezomib, and dexamethasone combination as induction therapy was effective with manageable side effects for the treatment of patients with newly diagnosed transplant-eligible MM.

This study was sponsored by Sanofi, the manufacturer of isatuximab and Bristol Myers Squibb (Celgene). The follow-up period was too short and the study did not include data on survival without cancer worsening.