Johnson & Johnson’s Darzalex is approved as part of a combination to treat newly diagnosed multiple myeloma patients eligible for stem cell transplant. But could extended treatment with the drug as a maintenance therapy improve patients’ outcomes? Early data aren’t very encouraging.
In transplant-eligible multiple myeloma patients whose tumors shrank by 50% on a Darzalex combo regimen—known as a partial response—maintaining treatment with solo Darzalex didn’t beat simple observation at fending off progression of their disease
The data, to be presented at the virtual American Society of Clinical Oncology meeting next month, came from part 2 of the phase 3 Cassiopeia trial. Patients had received either a combination of Takeda’s Velcade, thalidomide and dexamethasone (VTd) or that regimen plus Darzalex. They were treated both before and after transplant—during the so-called induction and consolidation phases—for part 1 of the study, which earned Darzalex its front-line transplant-eligible approval.
In patients who achieved a partial response while on the VTd regimen, continued Darzalex treatment did slash the risk of progression or death by 68% after a median follow-up of 35.4 months. But as the trial investigators pointed out, in patients who had received VTd plus Darzalex in the first phase of the study, progression-free survival was similar between patients who took Darzalex maintenance therapy and those who were simply watched for progression after their combo therapy stopped.
RELATED: ASH: Johnson & Johnson shores up Darzalex's myeloma lead with another subcutaneous win
But Craig Tendler, vice president of oncology clinical development & global medical affairs at J&J’s Janssen unit, used the trial as evidence to support early use of Darzalex. He noted that more patients in the VTd group dropped out of the trial during induction than the Darzalex-VTd arm did. That finding supports front-line Darzalex use “because if you don’t use it up front, then there’s a smaller group of patients that could end up benefiting from Darzalex maintenance,” he said during an interview.
Tendler was also quick to point out several elements in the study to support his argument that it’s still too early to reject the idea of Darzalex as a first-line maintenance therapy, even in multiple myeloma patients who already got it during induction and consolidation.
For one thing, Cassiopeia will continue, to determine how long it takes for patients’ tumors progress on next-line treatment—a marker known as second progression-free survival—and to see whether Darazelx maintenance prolongs patients’ lives.
What’s more, the Cassiopeia trial treated part 2 patients with Darzalex every eight weeks for two years, while other Darzalex trials have adopted an increased dosing frequency of every month for the maintenance phase. Plus, after Cassiopeia began, Bristol Myers Squibb’s Revlimid established itself as a standard of care for front-line maintenance treatment, Tendler noted.
RELATED: Sanofi's Sarclisa forays into Darzalex's new territory with FDA nod in earlier myeloma
J&J’s testing Darzalex against both theories in a phase 3 trial dubbed Perseus. It’s evaluating whether adding a recently approved under-the-skin version of Darzalex to a combo of Velcade, Revlimid and dexamethasone (VRd) would work in patients with previously untreated multiple myeloma.
In what Tendler called the “optimal maintenance strategies,” they will receive either solo Revlimid or its combo with monthly Darzalex during maintenance. J&J intends to use data from that study for labeling updates with regulatory authorities, Tendler said.
Darzalex lately started to face an in-class rival, Sanofi’s Sarclisa. The new CD38-directed antibody is following in Darzalex’s footsteps in moving up the treatment line.
In March, about a year after its original third-line green light, Sarclisa snatched an FDA go-ahead to be paired with Amgen’s Kyprolis and dexamethasone (Kd) for multiple myeloma after at least one prior therapy. A similar pairing of Kd with Darzalex was approved in that setting in August. The Sanofi drug has yet to enter front-line treatment.