Darzalex (daratumumab) combination regimen significantly improved outcomes for newly diagnosed multiple myeloma patients who are transplant ineligible.
Data from the Janssen Research & Development Phase 3 ALCYONE study, showed that Darzalex (daratumumab) in combination with bortezomib, melphalan, and prednisone (VMP) significantly improved clinical outcomes, including reducing the risk of disease progression or death by 50 percent, in patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplantation (ASCT).1
These data were presented as a late-breaking abstract at the 59th American Society of Hematology (ASH) Annual Meeting in Atlanta (Abstract #LBA-4). Study findings were simultaneously published in the New England Journal of Medicine.
“These Phase 3 results for Darzalex demonstrated clinically meaningful improvements with a manageable safety profile,” said Dr. Maria-Victoria Mateos, Ph.D., lead ALCYONE study investigator and director of the myeloma unit at University Hospital of Salamanca-IBSAL, Salamanca, Spain. “Selecting the right treatment regimen is critical for patients who are newly diagnosed, especially if they are transplant ineligible, as these patients tend to be older and more frail. These findings strongly support this Darzalex frontline regimen as a new standard of care for these patients.”
At a median follow-up of 16.5 months, Darzalex-VMP reduced the risk of disease progression or death by 50 percent, compared to treatment with VMP alone (Hazard Ratio [HR] = 0.50; 95 percent CI [0.38-0.65], p<0.0001).1 The median progression-free survival (PFS) for Darzalex-VMP had not yet been reached, compared to an estimated median PFS of 18.1 months for patients who received VMP alone.1
In addition to reducing the risk of disease progression or death, Darzalex significantly improved overall response rates (ORR) (91 percent vs. 74 percent) compared to VMP alone, including more than doubling rates of stringent complete response (sCR) (18 percent vs. 7 percent) and significantly improving rates of very good partial response (VGPR) or better (71 percent vs. 50 percent) and complete response (CR) or better (43 percent vs. 24 percent).1
Patients receiving Darzalex also reported a more than three-fold increase in the minimal residual disease (MRD) negativity rate (22 percent vs. 6 percent) compared to those who received VMP alone.1
The most common (≥10 percent) Grade 3/4 treatment-emergent adverse events (TEAEs) for Darzalex-VMP vs. VMP were neutropenia (40 percent vs. 39 percent), thrombocytopenia (34 percent vs. 38 percent), anemia (16 percent vs. 20 percent) and pneumonia (11 percent vs. 4 percent).1
One patient in each arm discontinued treatment due to pneumonia, and 0.9 percent of patients discontinued Darzalex due to an infection.1 Twenty-eight percent of patients experienced infusion reactions (IRs) due to Darzalex.1 In the Darzalex-VMP arm, 42 percent of patients experienced a serious adverse event (SAE), compared to 33 percent in the VMP arm.1
The most common (≥2 percent) SAEs were pneumonia (10 percent vs. 3 percent), anemia (2 percent vs. 3 percent), bronchitis (2 percent vs. 1 percent), lower respiratory tract infection (2 percent vs. 1 percent), upper respiratory tract infection (2 percent vs. 1 percent), febrile neutropenia (1 percent vs. 2 percent) and cardiac failure (<1 percent vs. 2 percent) for Darzalex-VMP vs. VMP, respectively.1
“Darzalex offers compelling and consistent clinical benefit across all lines of therapy in multiple myeloma,” said Sen Zhuang, M.D. Ph.D., vice president, oncology clinical research, Janssen Research & Development. “These latest results convey the promise of Darzalex in newly diagnosed patients for whom the initial therapy is most critical for long-term survival.”
On November 21, 2017, Janssen submitted a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) for Darzalex in combination with VMP for this patient population. Janssen requested Priority Review of this sBLA, which would shorten FDA review to six months, compared to 10 months for Standard Review.
If approved, this would be the fifth indication for Darzalex in the U.S. and its first in the frontline setting. On November 21, 2017, Janssen also submitted an application for this patient population to the European Medicines Agency.
1 Mateos M., et all. Phase 3 Randomized Study of Daratumumab Plus Bortezomib, Melphalan, and Prednisone (De-VMP) Versus Bortezomib, Melphalan, and Prednisone (VMP) in Newly Diagnosed Multiple Myeloma (NDMM) Patients Illegible for Transplant (ALCYONE). ASH 2017. Abstract #LBA-4.
(Source: Janssen Biotech, Inc.)
Filed Under: Drug Discovery