Darzalex combo OK’d for multiple myeloma transplant-eligible patients
Approval in EU expands indications for drug's subcutaneous formulation
The subcutaneous (under-the-skin) formulation of Darzalex (daratumumab) has been approved in the European Union as part of a combination treatment for adults with newly diagnosed multiple myeloma who qualify for an autologous hematopoietic stem cell transplant (AHSCT), expanding its number of approved indications in the region.
The treatment regimen includes subcutaneous Darzalex, which is marketed in the U.S. as Darzalex Faspro, with a standard combination of bortezomib, lenalidomide, and dexamethasone, also known as VRd. Bortezomib is branded as Velcade and is available as generics, while lenalidomide is marketed as Revlimid and as generics.
“The European Commission’s approval of this [subcutaneous Darzalex] quadruplet regimen marks a pivotal step forward in the treatment of newly diagnosed multiple myeloma,” Edmond Chan, MD, senior director and therapeutic lead of hematology for the Europe, Middle East, and Africa region at Johnson & Johnson Innovative Medicine, the therapy’s developer, said in a company press release.
“Since its first approval in 2016, over half a million patients worldwide have been treated with [Darzalex], and today’s approval reinforces our commitment to bringing this transformative therapy to more patients as a first-line treatment, where it has the greatest potential for impact,” said Jordan Schecter, MD, area lead of multiple myeloma at Johnson & Johnson Innovative Medicine.
Expanding indication of quadruplet therapy
The European Commission is reviewing a possible expansion of the quadruplet therapy’s indication to also cover newly diagnosed patients for whom an autologous hematopoietic stem cell transplant (AHSCT) wasn’t initially planned. An AHSCT is a common treatment for myeloma. The U.S. Food and Drug Administration has also approved the combo as a first-line treatment for those eligible for an AHSCT and is weighing extending it to those in whom a transplant wasn’t planned.
Should either regulatory agency approve the requests, the subcutaneous Darzalex-VRd combo could be used as a first-line therapy regardless of’ transplant eligibility.
Multiple myeloma forms from abnormal plasma cells, the activated and mature form of B-cells, a type of immune cell. This type of cancer can be difficult to treat because it’s often resistant to available treatment options. It also frequently relapses, meaning it can return after treatment.
“Multiple myeloma is a complex and highly varied disease, which reinforces the need for continuous innovation in first-line treatment strategies to deepen responses, reduce relapse, and ultimately improve long-term outcomes,” said Paula Rodriguez-Otero, MD, of the University of Navarra in Pamplona, Spain.
Darzalex binds to CD38, a protein present in high amounts on the surface of all B-cells, including the cancer cells that grow out of control in multiple myeloma. When Darzalex attaches to the protein, it activates the immune system to destroy the abnormal plasma cells, which should ease symptoms.
For patients who qualify for an AHSCT, first-line treatment may involve a couple of steps. Before the procedure, induction treatment seeks to reduce the number of cancer cells. Next, the consolidation step is a shorter round of the same treatment regimen that’s intended to clear any remaining cancer cells. Other medications may be prescribed to keep the cancer from returning.
Adding subcutaneous Darzalex to this regimen further optimizes “frontline therapy for patients” and builds on efforts to improve outcomes, and “establish new standards of care for eligible patients from induction through to maintenance,” Chan said. Treatment maintenance refers to the post-consolidation step.
A ‘new option’ in treating multiple myeloma
The request for expanded indication in the European Union was based on data from PERSEUS (NCT03710603), an ongoing Phase 3 clinical trial that enrolled 709 adults with newly diagnosed multiple myeloma and were eligible for an AHSCT.
The patients were randomly assigned to the standard VRd combination alone or along with subcutaneous Darzalex, all given for four cycles as induction treatment before the AHSCT and for two cycles as consolidation treatment afterward. Subcutaneous Darzalex is also given as maintenance treatment once every four weeks until the disease progresses or there is unacceptable toxicity.
The goal is to evaluate how long patients lived without their cancer getting worse.
After a median of 47.5 months, or nearly four years, a significantly higher proportion of patients treated with the quadruplet regimen lived without their cancer getting worse, with their risk of disease progression or death being 58% lower relative to those treated with the VRd combo.
The quadruplet treatment also resulted in significantly higher rates of a complete response or better (87.9% vs. 70.1%) and minimal residual disease (MRD) negativity, which refers to an absence of a small number of cancer cells that may remain after treatment and drive relapses (75.2% vs. 47.5%).
The overall safety profile of the subcutaneous Darzalex-VRd combo was consistent with the known safety profiles for each regimen.
Rodriguez-Otero, who consulted for the company, said the quadruplet regimen’s approval “offers a practice-changing new option that has shown the potential to significantly improve progression-free survival, complete response rates, and MRD-negativity status compared to the current standard of care.”
About the Author
