The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.
The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the service.
Like many types of malignancies, further treatment of multiple myeloma after relapsed, progressive, or refractory disease usually yields a shorter duration and lower quality of response compared to the initial response. There is a high demand for agents that treat multiple myeloma that does not respond or that progresses after first- or subsequent-line therapy.
Isatuximab-irfc (Sarclisa®) was approved by the US Food and Drug Administration (FDA) on March 2, 2020 in combination with pomalidomide and dexamethasone for the treatment of adult individuals with multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor.
Isatuximab-irfc (Sarclisa®) is a CD38-directed cytolytic antibody. CD38 is a glycoprotein expressed on the surface of hematopoietic cells (including lymphoid and myeloid cells) and tumor cells. When multiple myeloma is present, there is an overexpression of CD38 on malignant plasma cells. Isatuximab-irfc (Sarclisa®) works by binding to CD38 and induces apoptosis of tumor cells and activation of immune effector mechanisms including complement-dependent cytotoxicity (CDC) (causing tumor cell lysis and death), antibody-dependent cell-mediated cytotoxicity (ADCC) (causing tumor cell death by non-phagocytic processes via the activation of natural killer cells, macrophages, etc.), and antibody-dependent cellular phagocytosis (ADCP) by macrophages. The combination of isatuximab-irfc (Sarclisa®) and pomalidomide enhanced ADCC activity and direct tumor cell killing compared to that of isatuximab-irfc (Sarclisa®) alone in vitro, and the combination of isatuximab-irfc (Sarclisa®) and pomalidomide also enhanced antitumor activity compared to the activity of isatuximab-irfc (Sarclisa®) or pomalidomide alone in a human multiple myeloma xenograft model.
The safety and efficacy of isatuximab-irfc (Sarclisa®) were evaluated in ICARIA-MM (Attal et al 2019), a multicenter, multinational, randomized (1:1), open-label, two-arm, phase 3 study in 307 adult individuals with relapsed and refractory multiple myeloma. Individuals had received at least two prior therapies including lenalidomide and a proteasome inhibitor (e.g., bortezomib [Velcade®], carfilzomib [Kyprolis®], ixazomib [Ninlaro®]). The median number of prior lines of therapy was 3 (range 2-11). All participants received a prior proteasome inhibitor, all participants received prior lenalidomide, and 56% of participants received prior stem cell transplantation; the majority of participants (93%) were refractory to lenalidomide, 76% to a proteasome inhibitor, and 73% to both an immunomodulator and a proteasome inhibitor. The median age was 67 years (range 36-86).
Participants received either isatuximab-irfc (Sarclisa®) 10 mg/kg (as an intravenous infusion weekly in the first cycle and every two weeks thereafter) in combination with pomalidomide 4 mg and dexamethasone 40 mg (20 mg for individuals aged ≥75 years) (Isa-Pd, N=154) or pomalidomide 4 mg and dexamethasone 40 mg (Pd, N=153). Treatment was administered in both groups in 28-day cycles until disease progression or unacceptable toxicity, or consent withdrawal.
The primary outcome of this study was progression-free survival (PFS). At a median follow-up time of 11.6 months, the Isa-Pd group had a higher median progression-free survival (11.5 versus 6.5 months, p=0.001) compared to the Pd group. PFS benefit with Isa-Pd occurred in the following prespecified subgroups: individuals with poor prognosis, aged 75 years or older, disease refractory to lenalidomide, a proteasome inhibitor, both lenalidomide and a proteasome inhibitor, or to lenalidomide at the last line prior to study entry. The median duration of treatment was 41 weeks for the Isa-Pd group compared to 24 weeks for the Pd group. There was a high number of participants who discontinued treatment: 87 out of 152 individuals in the Isa-Pd group and 114 out of 149 individuals in the Pd group, although all 307 individual were included in the intention-to-treat analysis. The most frequent treatment-emergent adverse events (any grade) were infusion reactions, upper respiratory tract infections, and diarrhea.
There may be additional indications contained in the Policy section of this document due to evaluation of criteria highlighted in the Company’s off-label policy, and/or review of clinical guidelines issued by leading professional organizations and government entities.
C90.00 Multiple myeloma not having achieved remission
C90.01 Multiple myeloma in remission
C90.02 Multiple myeloma in relapse
Policy: MA08.012c:Off-label Coverage for Prescription Drugs and/or Biologics
Policy: MA08.037f:Bortezomib (Bortezomib for Injection, Velcade®)
Policy: MA08.062d:Carfilzomib (Kyprolis™)
Policy: MA08.079e:Daratumumab (Darzalex™)