The REST study
Dr Frida Bugge Askeland, associated research doctor and PhD student at the Oslo Myeloma Center in Norway summarised the REST study.
In Norway, the use of VRd (bortezomib, lenalidomide and dexamethasone) or Rd alone represents the standard of care for patients with newly diagnosed multiple myeloma (NDMM) who are ineligible for transplant. The MAIA trial demonstrated that adding a CD38 monoclonal antibody to Rd results in better and deeper responses and prolonged PFS.
The REST study evaluated isatuximab (Isa) combined with VRd as first-line treatment in transplant-ineligible NDMM patients with a median age of 77 years. Isa was introduced as a replacement for corticosteroids in the Isa-VRd regimen. The rationale behind limiting or substituting corticosteroids in MM treatment stems from their potential to adversely impact both short-term and long-term quality of life, while also increasing susceptibility to infections. Infections emerge as a predominant cause of complications and mortality, with an escalating incidence correlated to age. In the REST study, bortezomib was administered on a once-weekly basis for the initial eight cycles. Notably, only six cases of peripheral neuropathy attributable to bortezomib were observed, comprising three cases of grade 2 severity and three cases of grade 3 severity. Adverse events primarily manifested as infections and neutropenia. The majority of infections were categorized as grade 2. The predominant haematological toxicity observed was neutropenia, with a significant proportion graded as level 3. Many patients received growth-stimulating factors to manage this haematological toxicity. After a median follow-up of 12 months, the ORR was reported at 100%, with a very good partial response or better achieved in 80.3% of cases.
In conclusion, the Isa-VRd regimen demonstrates a well-tolerated safety profile and promising preliminary efficacy in transplant-ineligible NDMM patients with a median age of 77 years. Follow-up is ongoing.
Reference:
Askeland F, ASH 2023. #3381
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