Isatuximab Is Safe and Effective for Previously Treated AL Amyloidosis

Therapy with isatuximab for previously treated light-chain (AL) amyloidosis was found to be effective and safe, according to data presented at the American Society of Hematology 2020 virtual annual conference (abstract #728)

Isatuximab is an anti-CD38 IgG1κ monoclonal antibody used in the treatment of relapsed or refractory multiple myeloma. The drug’s efficacy for AL amyloidosis therapy was tested in a prospective, multi-center, phase II study.

This trial enrolled 35 adults with relapsed or refractory systemic AL amyloidosis who received at least one prior line of therapy. Median participant age was 70 years (range 40-81) and prior therapies included proteasome inhibitors (89%), high-dose therapy followed by autologous hematopoietic cell transplant (47%), immunomodulatory therapy (25%), or anti-CD38 monoclonal antibody therapy (6%). Nineteen patients had single organ involvement and seventeen patients had at least two organs involved. Renal and cardiac involvement were seen in 16 and 24 patients, respectively.

Isatuximab was administered intravenously weekly, dosed at 20 mg/kg, for a 28-day cycle, followed by bi-weekly administration for a maximum of 24 cycles. The primary endpoint was hematologic response and secondary outcomes included organ response, safety, progression-free survival, and overall survival.

Median treatment duration was 11.8 months (range, 0.3-22.1). Nineteen patients discontinued treatment due to adverse events (AEs; 26%), disease progression (21%), sub-optimal response (11%), or concerns related to COVID-19 (11%). The current median follow-up is 16.3 months.

Overall hematologic response rate was 77%, with a complete response achieved in 1 patient (3%), a very good partial response in 19 patients (54%), a partial response in 7 patients (20%). The most common treatment-related AEs occurring in more than 20% of patients included infusion related reactions, anemia, and lymphopenia.

“Isatuximab demonstrates encouraging efficacy in previously treated patients with AL amyloidosis. The administration of isatuximab in these patients is associated with a good safety profile similar to other monoclonal antibodies against CD38,” the researchers concluded.