Primary outcomes by 1q21+ status for isatuximab-treated patients with relapsed/refractory multiple myeloma: subgroup analyses from ICARIA-MM and IKEMA
Abstract
Gain/amplification of 1q21, referred to as 1q21+ in this letter, is one of the most common chromosomal abnormalities in multiple myeloma (MM), being detected in approximately 40% of patients at diagnosis. The number of MM cells with 1q21+ and the number of copies of 1q21+ increases as the disease progresses.
Furthermore, its negative impact on prognosis suggests that 1q21+ is involved in the pathophysiology of disease progression and resistance to MM treatment. The 1q21+ abnormality is defined as gain of 1q21 (gain[1q21], 3 copies) and amplification of 1q21 (amp[1q21], >=4 copies).
Co-existence of certain high-risk chromosomal abnormalities is common and further worsens the prognosis for patients with 1q21+. In the phase III studies ICARIA-MM and IKEMA, the addition of the anti-CD38 monoclonal antibody isatuximab (Isa) to the backbone of pomalidomide-dexamethasone (Pd) or carfilzomib-dexamethasone (Kd), respectively, improved progression-free survival (PFS) among patients with relapsed/refractory MM, and subgroup analyses suggested benefit among patients with 1q21+.
The current analyses examine four subgroups of patients from ICARIA-MM and IKEMA: 1q21+ (>=3 copies with or without high-risk chromosomal abnormalities), isolated 1q21+ (>=3 copies without high-risk chromosomal abnormalities), gain(1q21) (3 copies with or without high-risk chromosomal abnormalities), and amp(1q21) (>=4 copies with or without high-risk chromosomal abnormalities). The analyses show a clear benefit of Isa-based combinations in 1q21+ disease.