The phase 3 ALCYONE study showed the addition of daratumumab to bortezomib, melphalan and prednisone (D-VMP) improved OS in patients with newly diagnosed, transplant-ineligible multiple myeloma, with a 40 percent reduction in the risk of death compared to VMP alone.
These updated data from the ALCYONE study also demonstrated that the addition of daratumumab to VMP resulted in higher rates of minimal residual disease (MRD) negativity.
These data are the first OS results from the ALCYONE study and are being featured during an oral session at the 2019 American Society of Hematology (ASH) Annual Meeting in Orlando.
The data were simultaneously published in The Lancet.
“As a physician treating patients with multiple myeloma, I want to achieve the deepest response in the frontline setting to hopefully provide long-term benefit,” said Maria-Victoria Mateos, M.D., Ph.D., Director of the Myeloma Unit at University Hospital of Salamanca-IBSAL, Salamanca, Spain, and a study investigator.
“This longer follow-up from the ALCYONE study is encouraging because we see that adding daratumumab to VMP in the frontline setting can provide an important overall survival advantage compared with a current standard of care.”
Results of a pre-specified interim analysis, after a median duration of follow-up of more than three years, showed an estimated 42-month OS rate of 75 percent for daratumumab-VMP versus 62 percent for VMP, with a statistically significant improvement in OS observed for daratumumab-VMP versus VMP alone (hazard ratio [HR]=0.60; 95 percent confidence interval [CI], 0.46-0.80; P=0.0003).
Of note, median OS was not assessed in either group and follow-up is ongoing.
In addition, daratumumab-VMP resulted in a median progression-free survival (PFS) of 36.4 months versus 19.3 months with VMP alone after a median follow-up of 40.1 months (HR=0.42; 95 percent CI, 0.34-0.51; P<0.0001).
The results also demonstrated that daratumumab-VMP achieved significantly higher rates of MRD-negativity compared to VMP alone (28 percent vs. 7 percent, respectively) at a threshold of one tumour cell per 10-5 white cells.
The most common Grade 3/4 treatment-emergent adverse events (TEAEs) occurring in ≥3 percent for D-VMP arm compared to the VMP arm included neutropenia (40.2 percent vs. 39 percent), thrombocytopenia (34.7 percent vs. 37.9 percent), anaemia (17.3 percent vs. 19.8 percent) and pneumonia (13 percent vs. 4.2 percent).
Grade 5 TEAEs were 6.9 percent in the D-VMP treatment arm compared with 5.6 percent in the VMP arm and discontinuation due to TEAEs was 6.9 percent in the D-VMP arm vs. 9.3 percent in the VMP arm, and the rate of invasive second primary malignancy in D-VMP vs. VMP were 4.9 percent vs. 4.5 percent, respectively.
No new safety concerns were identified.
Additional data from longer follow-up (median of 36.4 months) from the Phase 3 MAIA study presented at ASH 2019 demonstrated daratumumab in combination with lenalidomide and dexamethasone (D-Rd) continued to significantly reduce the risk of disease progression or death by ≥44 percent in patients with newly diagnosed multiple myeloma who are transplant ineligible, compared to treatment with Rd alone (HR = 0.56; 95 percent CI: 0.44-0.71; P<0.0001), with no new safety concerns after three years of follow-up with D-Rd.
Additionally, time from randomisation to progression on next-line treatment or death (PFS2) favoured the daratumumab arm (HR = 0.69; 95 percent CI, 0.53-0.91; P=0.0079).
Common Grade 3/4 TEAEs occurring in ≥10 percent of patients in the daratumumab-Rd arm compared to the Rd arm were neutropenia (51 percent vs. 35 percent), lymphopenia (15 percent vs. 11 percent), pneumonia (15 percent vs. 9 percent), anaemia (14 percent vs. 21 percent), leukopenia (11 percent vs. 6 percent) and hypokalemia (10 percent vs. 10 percent), respectively.
The most common serious TEAE in the daratumumab-Rd arm compared to the Rd arm was pneumonia (14 percent vs. 9 percent, respectively).
The most common Grade 3/4 infection rates were 36 percent in the daratumumab-Rd treatment arm compared with 27 percent in the Rd arm.
In the daratumumab-Rd arm, 9 percent of patients discontinued treatment due to TEAEs, compared with 18 percent of patients in the Rd arm.
“The data we are presenting at ASH demonstrate the benefit of daratumuab-based regimens in the frontline setting as supported by deep, durable responses and significantly prolonged survival,” said Yusri Elsayed, M.D., MHSc., Ph.D., Vice President, Hematologic Malignancies Disease Area Leader, Janssen Research & Development, LLC. “We remain committed to the study of daratumumab with the goal of making a difference in the lives of patients diagnosed with multiple myeloma.”