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Health Canada has approved daratumumab injection, a subcutaneous formulation of daratumumab, for use in combination with bortezomib, cyclophosphamide, and dexamethasone in the treatment of patients with newly diagnosed light chain amyloidosis.
Health Canada has approved daratumumab injection (Darzalex SC), a subcutaneous formulation of daratumumab (Darzalex), for use in combination with bortezomib, cyclophosphamide, and dexamethasone (D-VCd; VCd) in the treatment of patients with newly diagnosed light chain (AL).1
The regulatory decision is based on data from the phase 3 ANDROMEDA trial (AMY3001), which demonstrated that D-VCd resulted in a hematologic complete response (CR) rate that was almost triple that of VCd alone in this population, at 53% vs 18%, respectively (P <.0001).
“AL amyloidosis is rare and can present differently from person to person, yet many patients experience organ deterioration or failure by the time they are diagnosed. I hope this approval can lead to greater awareness of this disease and the importance of early diagnosis and treatment,” Victor Zepeda, MD, assistant professor of medicine at the University of Calgary and clinician scientist at the Arnie Charbonneau Cancer Institute, stated in a press release. “Patients with this disease have extremely limited options, and today’s approval of this subcutaneous formulation of daratumumab offers new hope for those with AL amyloidosis and their caregivers.”
In the open-label phase 3 ANDROMEDA trial, investigators examined the safety and efficacy of subcutaneous daratumumab in combination with VCd vs VCd alone in patients with newly diagnosed AL amyloidosis. A total of 388 patients were enrolled to the trial and all had measurable hematologic disease with 1 or more organs affected.
Study participants were given subcutaneous daratumumab at a once-weekly dose of 1800 mg from weeks 1 through 8, once every 2 weeks from weeks 9 through 24, and once every 4 weeks beginning on week 25 until either progressive disease, intolerable toxicity, or treatment completion at 2 years. Of those who received D-VCd, 74% were exposed to the regimen for 6 months or longer, while 32% were exposed for longer than 1 year.
The primary end point of the trial was complete hematologic response rate in the intent-to-treat population.
Additional data from the trial presented during the 2020 ASH Virtual Meeting showed that the D-VCd regimen significantly prolonged major organ deterioration–progression-free survival (MOD-PFS) compared with VCd alone.2 MOD-PFS events were observed in 17.4% (n = 34) of patients on the investigative arm vs 27.5% (n = 53) of those on the control arm (HR, 0.58; 95% CI, 0.36-0.93; P = .0211).
The most frequently reported treatment-emergent toxicities in the investigative arm included peripheral edema, fatigue, diarrhea, constipation, nausea, upper respiratory tract infection, peripheral sensory neuropathy, dyspnea, cough, insomnia, and anemia.
Serious treatment-emergent adverse effects were experienced by 5% of those on the investigative arm and included pneumonia, which was reported in 7% of patients, and cardiac failure, which was also reported in 7% of patients. Eleven percent of patients who received the quadruplet regimen experienced fatal adverse reactions; reactions that were reported in more than 1 patient comprised cardiac arrest (3%), sudden death (3%), cardiac failure (3%), and sepsis (1%).
In January 2021, the FDA approved daratumumab and hyaluronidase-fihj (Darzalex Faspro), a subcutaneous formulation of daratumumab, to be used in combination with VCd in patients with AL amyloidosis based on data from ANDROMEDA. Previously, in May 2020, Darzalex Faspro was FDA approvedfor use in adult patients with newly diagnosed or relapsed/refractory multiple myeloma based on data from the phase 3 COLUMBA trial (MMY3012).