Daratumumab/hyaluronidase

Daratumumab/hyaluronidase, sold under the brand name Darzalex Faspro, is a fixed-dose combination medication for the treatment of adults with newly diagnosed or relapsed/refractory multiple myeloma.^[2][1][3] It is a combination of daratumumab and hyaluronidase.^[1] It is administered via subcutaneous injection.^[1]

Daratumumab/hyaluronidase

Combination of
Daratumumab	CD38-directed cytolytic antibody
Hyaluronidase	Endoglycosidase
Clinical data
Trade names	Darzalex Faspro
License data	US DailyMed: Daratumumab and hyaluronidase
Routes of administration	Subcutaneous
ATC code	None
Legal status
Legal status	US: ℞-only[1]
Identifiers
KEGG	D11967

The most common adverse reaction using daratumumab/hyaluronidase as monotherapy is upper respiratory tracts infection.^[1] The most common adverse reactions (≥20%) in people with amyloid light-chain amyloidosis who received daratumumab/hyaluronidase in combination with bortezomib, cyclophosphamide, and dexamethasone are upper respiratory tract infection, diarrhea, peripheral edema, constipation peripheral sensory neuropathy, fatigue, nausea, insomnia, dyspnea and cough.^[4] The most common adverse reactions (≥20%) occurring in people treated with daratumumab/hyaluronidase, carfilzomib, and dexamethasone were upper respiratory tract infections, fatigue, insomnia, hypertension, diarrhea, cough, dyspnea, headache, pyrexia, nausea, and edema peripheral.^[5]

Medical uses

Daratumumab/hyaluronidase is indicated for the treatment of adults with multiple myeloma:^[2]

• in combination with bortezomib, melphalan and prednisone (D-VMP) in newly diagnosed adults who are ineligible for autologous stem cell transplant^[1][2]
• in combination with lenalidomide and dexamethasone (D-Rd) in newly diagnosed adults who are ineligible for autologous stem cell transplant and in people with relapsed or refractory multiple myeloma who have received at least one prior therapy^[1][2]
• in combination with bortezomib and dexamethasone (D-Vd) in adults who have received at least one prior therapy^[1][2]
• as monotherapy, in adults who have received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory agent.^[1][2]

In January 2021, the US Food and Drug Administration (FDA) granted accelerated approval to daratumumab/hyaluronidase in combination with bortezomib, cyclophosphamide, and dexamethasone for newly diagnosed amyloid light-chain amyloidosis.^[4]

In November 2021, the FDA granted approval to daratumumab/hyaluronidase in combination with carfilzomib plus dexamethasone to treat relapsed or refractory multiple myeloma in adults who have received one to three prior lines of therapy.^[5]

In August 2024, the FDA granted approval to daratumumab/hyaluronidase in combination with bortezomib, lenalidomide, and dexamethasone for induction and consolidation in people with newly diagnosed multiple myeloma who are eligible for autologous stem cell transplant (ASCT).^[6]

History

It was approved for use in the United States in May 2020.^[2][7][8]

Efficacy of daratumumab and hyaluronidase-fihji (monotherapy) was evaluated in the COLUMBA trial (NCT03277105), an open-label non-inferiority trial randomizing 263 participants to daratumumab and hyaluronidase-fihj and 259 to intravenous daratumumab (daratumumab IV).^[2] The trial's co-primary endpoints were overall response rate (ORR) and pharmacokinetic (PK) endpoint of the maximum Ctrough on cycle 3, day 1 pre-dose.^[2] Daratumumab and hyaluronidase-fihj was non-inferior to daratumumab IV in evaluating these two endpoints.^[2]

Efficacy of daratumumab and hyaluronidase-fihj in combination with VMP (D-VMP) was evaluated in a single-arm cohort of the PLEIADES trial (NCT03412565), a multi-cohort, open‑label trial.^[2] Eligible participants were required to have newly diagnosed multiple myeloma and were ineligible for transplant.^[2]

Efficacy of daratumumab and hyaluronidase-fihj in combination with Rd (D-Rd) was evaluated in a single-arm cohort of this trial.^[2] Eligible participants had received at least one prior line of therapy.

Efficacy of daratumumab/hyaluronidase in combination with bortezomib, cyclophosphamide, and dexamethasone was evaluated in ANDROMEDA (NCT03201965), an open-label, randomized, active-controlled trial in 388 participants with newly diagnosed amyloid light-chain amyloidosis with measurable disease and at least one affected organ according to consensus criteria.^[4] Participants were randomized to receive bortezomib, cyclophosphamide, and dexamethasone (VCd arm) or with daratumumab and hyaluronidase (D-VCd arm).^[4]

Efficacy of daratumumab/hyaluronidase in combination with carfilzomib and dexamethasone was evaluated in PLEIADES (NCT03412565), a multi-cohort, open-label trial.^[5]