Dramatically Deepened Responses For Myeloma Patients– Mt Sinai’s Dr. Richter On Using Darzalex As A Shot For Newly Diagnosed Patients

A breakthrough clinical trial published in the New England Journal of Medicine (PERSEUS trial) has paved a new horizon for newly diagnosed patients with multiple myeloma (MM). The authors found that adding Darzalex (daratumumab) to the standard treatment was better than offering the standard treatment alone. 

In an interview with SurvivorNet, Dr. Joshua Richter, an associate professor of medicine at the Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, and the director of myeloma at the Blavatnik Family Chelsea Medical Center at Mount Sinai, talked about the benefits and further expectations with this new therapy. 

“We’re really excited about the recent FDA approval of subcutaneous Darzalex along with the RVD backbone for newly diagnosed multiple myeloma patients who are eligible for stem cell transplant, ” he says. 

For patients who are newly diagnosed with multiple myeloma, the standard treatment typically involves a multifaceted approach that begins with a combination of various drugs and is followed by a stem cell transplant. 

This treatment paradigm has been established for more than a decade. Throughout this period, ongoing research has focused on optimizing the drug regimen by introducing new agents or adjusting existing therapies to improve cancer control and extend the period of remission. 

Daratumumab: Subcutaneous versus Intravenous Route

Daratumumab, a monoclonal antibody targeting multiple myeloma cells, not only directly induces cell death but also enhances the recruitment of immune cells to further attack the cancer. This drug can be administered either intravenously or subcutaneously. 

Both administration methods are effective against multiple myeloma; however, subcutaneous injections are associated with fewer adverse effects and significantly reduce treatment time for patients, with lower rates of infusion-related reactions, rapid administration time, similar drug cost, and lower total administration costs. While intravenous infusions require several hours to complete, subcutaneous injections are administered within a few minutes. The PERSEUS trial employed subcutaneous daratumumab, reflecting this shift in clinical practice.

“This is based on the phase three randomized per se study which compared Daratumumab + RVD (bortezomib, lenalidomide, and dexamethasone) versus RVD as induction therapy for transplant-eligible newly diagnosed multiple myeloma patients,” Dr. Richter tells SurvivorNet. 

Who Should Receive  Subcutaneous  Daratumumab + Standard Treatment? 

The PERSEUS Trial involved more than 700 individuals with newly diagnosed multiple myeloma. Participants, all of whom were eligible for stem cell transplantation—indicating they were generally younger and in good overall health—were randomly assigned to receive a standard treatment regimen (bortezomib, lenalidomide, and dexamethasone)  either with or without the addition of subcutaneous daratumumab. 

Patients in the daratumumab group received the drug during the induction, consolidation, and maintenance phases of their treatment.

Over a median follow-up period of nearly four years, the outcomes for patients were closely monitored using various metrics. Across all measures, the combination of the standard regimen plus daratumumab outperformed the standard regimen alone.

Specifically, patients who received daratumumab exhibited higher rates of deep responses, such as complete or stringent complete responses (indicating no detectable signs of cancer through conventional blood tests and other diagnostics) and minimal residual disease (MRD) negativity (no detectable cancer using highly sensitive DNA tests).

Key findings from the study include:

• Progression-free survival at 4 years: 84% in the daratumumab group vs. 68% in the standard treatment group.
• Complete or stringent complete response rates: 88% with daratumumab vs. 70% with standard treatment.
• MRD negativity: 75% in the daratumumab group compared to 48% in the standard treatment group.
• MRD negativity for at least 1 year: 65% with daratumumab vs. 30% with standard treatment.

It is worth noting that adding daratumumab increased the rates of neutropenia, thrombocytopenia, and infections. Stem cell mobilization and collection were feasible with this four-drug regimen, although a higher percentage of patients received plerixafor for mobilization (40 versus 23 percent). 

A greater proportion of patients in the daratumumab group experienced serious side effects compared to those in the standard treatment group (57% versus 49%). Despite this, a smaller percentage of patients in the daratumumab group discontinued treatment due to these side effects (9% versus 22%).

“What’s really exciting about this is that for many years, triplets have been the standard myeloma regimens such as RVD, but now, with the addition of Darzalex, we’re able to add initially a once-a-week subcutaneous administration drug, which dramatically deepens responses and overall leads to better outcomes for newly diagnosed patients, thus making quadruplets the new standard of care in newly diagnosed myeloma,” explain Dr. Richter.