FDA adds Darzalex Faspro to combo therapy for newly diagnosed MM
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The U.S. Food and Drug Administration (FDA) has approved a new quadruple regimen including Darzalex Faspro (daratumumab and hyaluronidase-fihj) as a first-line approach for adults with newly diagnosed multiple myeloma and eligible for a stem cell transplant.
Johnson & Johnson’s Darzalex Faspro now can be used in combination with a standard triple-therapy regimen known as VRd both before (induction) and after (consolidation) autologous stem cell transplant to deepen therapeutic responses.
VRd comprises bortezomib (sold as Velcade, with generics available), lenalidomide (sold as Revlimid and generics), and dexamethasone. Darzalex Faspro is an under-the-skin, or subcutaneous, injection formulation of Darzalex (daratumumab), an older myeloma therapy that is infused directly into the bloodstream.
“Today’s approval embodies our commitment to setting new standards of care for patients newly diagnosed with multiple myeloma who are transplant eligible,” Jordan Schecter, MD, vice president and multiple myeloma area leader at Johnson & Johnson, said in a company press release.
Darzalex Faspro possible ‘foundational frontline therapy’ for multiple myeloma
The company believes the newly approved regimen establishes Darzalex Faspro as a “foundational frontline therapy” for multiple myeloma.
This latest FDA clearance represents the ninth approved myeloma indication for Darzalex Faspro in the U.S. It previously was approved, alone or as part of various regimens, as a first-line treatment for transplant eligible or ineligible adult patients, as well as in later lines of therapy.
The label expansion is supported by data from the Phase 3 PERSEUS clinical trial (NCT03710603), which showed that the Darzalex Faspro-VRd combo led to better outcomes than VRd alone among newly diagnosed, transplant-eligible multiple myeloma patients.
“This latest indication for Darzalex Faspro-based quadruplet therapy demonstrated a clinically significant reduction in disease progression or death during first-line treatment when patients are likely to experience their deepest responses,” Schecter said.
Johnson & Johnson also submitted a request for a similar label expansion in the European Union.
Autologous stem cell transplant is a standard approach for treating multiple myeloma, wherein a patient’s own stem cells are used to help repopulate the blood with healthy cells.
Before patients undergo a transplant, they’re often treated with other therapies to start depleting the body of myeloma cells (induction therapy). Another round of such treatment may be used after the transplant to deepen therapeutic responses (consolidation therapy).
Treatment targets CD38 protein, at high levels on surface of myeloma cells
These treatment regimens may include CD38 inhibitors, a class of medications that target the CD38 protein found at high levels on the surface of myeloma cells. By binding to and blocking the activity of CD38, they suppress cancer cell growth and cause the cells to die off.
Darzalex and Darzalex Faspro both contain daratumumab, a CD38 inhibitor. While Darzalex is given via infusions, Darzalex Faspro is given as a fixed-dose, subcutaneous administration that reduces the treatment time from hours to minutes and is associated with fewer administration-related side effects.
For its newly approved indication, Darzalex Faspro will be given via subcutaneous injections once weekly for two months, and then every other week for another two months in the four months prior to a stem cell transplant.
For post-transplant consolidation, it will be started again with injections once every two weeks for two months.
Quadruple combo lowered disease progression, death risk by 58% in Phase 3 trial
PERSEUS involved 709 transplant-eligible adults newly diagnosed with multiple myeloma. Four-year data showed that quadruple Darzalex Faspro and VRd therapy for induction and consolidation around the time of transplant led to better outcomes than VRd alone, lowering the risk of myeloma progression or death by 58%.
Moreover, a significantly higher proportion of patients on the Darzalex Faspro-VRd combo achieved a complete treatment response or better (87.9% vs. 70.1%) and was negative for minimal residual disease (75.2% vs. 47.5%) relative to those on VRd alone.
Minimal residual disease concerns the small number of cancer cells that can remain in a patient’s body after treatment, and ultimately drive cancer relapse and progression.
“The efficacy data supporting this new quadruplet regimen, combined with its established safety and tolerability profile, provide compelling evidence that adding [Darzalex Faspro-VRd] upon initial diagnosis … can deepen responses and prolong remissions in the context of autologous stem cell transplantation,” said Amrita Y. Krishnan, MD, professor and director of the Judy and Bernard Briskin Multiple Myeloma Center, part of the City of Hope cancer research institute based in Duarte, California.
The combination’s most common side effects include symptoms of nerve damage, fatigue, swelling, fever, upper respiratory infection, constipation, diarrhea, musculoskeletal pain, insomnia, and rash.
Darzalex Faspro should not be used in people with a history of severe allergic reactions to any of its ingredients.
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