FDA Approves Daratumumab Triplet for Previously Treated Multiple Myeloma

The FDA has granted approval to the combination of daratumumab and hyaluronidase-fihj (Darzalex Faspro) and pomalidomide and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior line of therapy, including lenalidomide and a proteasome inhibitor, according to a press release issued by The Janssen Pharmaceutical Companies of Johnson & Johnson.¹

Approval was granted to the combination based on results from the phase 2 APOLLO clinical trial (NCT03180736), which showed a reduction in the risk of disease progression or death when daratumumab and hyaluronidase-fihj were added to pomalidomide and dexamethasone.

"Clinical studies including APOLLO have continued to show the ability of daratumumab-based combination treatment regimens to significantly reduce the risk of progression in patients with multiple myeloma," said Meletios A. Dimopoulos, MD, professor and chairman of the Department of Clinical Therapeutics at the National and Kapodistrian University of Athens School of Medicine, Athens, Greece, and principal investigator. "With this approval, we are now able to combine pomalidomide and dexamethasone with a daratumumab subcutaneous option that can be administered in minutes rather than the hours needed for intravenous administration."

APOLLO is an open-label, randomized, phase 3 trial actively being conducted at 4 academic centers in 12 different countries in Europe. Those eligible to enroll were aged 18 years or older with relapsed or refractory multiple myeloma, measurable disease, an Eastern Cooperative Oncology Group performance status of 0 to 2, at least 1 previous line of therapy, including lenalidomide and a proteasome inhibitor, had a partial response or better to at least 1 prior line of antimyeloma therapy, and were refractory to lenalidomide if only 1 prior line of therapy was received. In total, 304 patients were randomized 1:1, assigning 151 patients to the experimental combination and 153 to the pomalidomide and dexamethasone arm.^1,2

The primary end point of the study is progression-free survival (PFS), and the secondary end points include overall response rate, achievement of very good partial response rate or, achievement of complete response or better, minimal residual disease negativity rate, time to response, duration for response, overall survival, safety determined by the incidence of adverse events, and other efficacy end points.

A 37% reduction in the risk of disease progression or death was achieved with daratumumab and hyaluronidase-fihj plus pomalidomide and dexamethasone, meeting the primary end point of the study (HR, 0.63; 95%CI, 0.47-0.85; P =.0018). The median PFS observed in the experimental arm was 12.4 months (95% CI 8.3-19.3) compared with 6.9 months (95% CI, 5.5-9.3) in the pomalidomide and dexamethasone arm (HR, 0.63; 95% CI 0.47-0.85], two-sided P =.0018).

Grade 3 AEs observed with the combination of daratumumab and hyaluronidase-fihj plus pomalidomide and dexamethasone vs. the doublet arm were neutropenia (68% vs 51%), anemia (17% vs 21%, and thrombocytopenia (17% vs 18%).

Further, serious AES was seen in 50% of the triplet arm versus 39% of the doublet arm. The most common serious AEs included pneumonia (15% vs 8%) and lower respiratory tract infection (12% vs 9%). Treatment-emergent deaths occurred in 7% of patients in each treatment arm. Two percent of the overall study population had permanent treatment discontinuation due to AEs.

"We are focused on the continued development of Darzalex Faspro and advancing this innovative therapy for patients who are in need of additional treatment options," said Craig Tendler, MD, vice president, Late Development and Global Medical Affairs, Janssen Research & Development, LLC. "Today's approval further distinguishes Darzalex FASPRO in the treatment of multiple myeloma as the first and only subcutaneously administered anti-CD38 monoclonal antibody approved in combination with the widely used pomalidomide and dexamethasone regimen."

_References:

_{1. Janssen announces U.S. FDA approval of DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) in combination with pomalidomide and dexamethasone for patients with multiple myeloma after first or subsequent relapse. News release. Janssen. July 12, 2021. Accessed July 12, 2021. https://bit.ly/3hz8VY9}

_{2. Dimopolous MA, Terpos E, Boccadoro M, et al. Daratumumab plus pomalidomide and dexamethasone versus pomalidomide and dexamethasone alone in previously treated multiple myeloma (APOLLO): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021;22(6): 801-812. doi: 10.1016/S1470-2045(21)00128-5}