Subcutaneous Daratumumab Indication Expanded to Include Pomalidomide/Dexamethasone Combo for Relapsed Myeloma

The FDA approved the combination of daratumumab and hyaluronidase-fihj plus pomalidomide/dexamethasone as therapy for certain patients with pretreated multiple myeloma.

The FDA has granted approval to daratumumab (Darzalex) and hyaluronidase-fihj (Darzalex Faspro), allowing providers to use the subcutaneous formulation in combination with pomalidomide (Pomalyst)/dexamethasone for patients with multiple myeloma who have received at least 1 prior line of therapy, including lenalidomide (Revlimid) and a proteasome inhibitor, according to the manufacturers of the individual agent, Halozyne Therapeutics, and Janssen Pharmaceutical Companies of Johnson & Johnson.1,2

The subcutaneous formulation of daratumumab is co-formulated with Halozyme’s ENHANZE drug delivery technology, consisting of recombinant human hyaluronidase PH20 (rHuPH20). This approval marks the sixth indication for this formulation of daratumumab in the treatment of multiple myeloma and was based on findings from the phase 3 APOLLO trial (NCT03180736).

“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,” Meletios A. Dimopoulos, MD, professor and chairman of the Department of Clinical Therapeutics at the National and Kapodistrian University of Athens School of Medicine in Athens, Greece, and principal investigator of the study, said in a press release. “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.”

In the open-label, multicenter trial, patients were randomized 1:1 to received daratumumab plus pomalidomide and dexamethasone (D-Pd; n = 151) or Pd alone (n = 153). The D-Pd regimen consisted of 1800 mg of subcutaneous daratumumab every week for cycles 1 and 2, bi-weekly for cycles 3 through 6, and every 4 weeks for cycle 7 and beyond; 4 mg pomalidomide on days 1 through 21 of each cycle; and 40 mg dexamethasone on days 1, 8, 15, and 22 of each cycle, and 20 mg for patients aged 75 or older. The median duration of subcutaneous administration was 5 minutes (range, 1-22).3,4

The addition of subcutaneous daratumumab significantly reduced the risk of progression or death by 37% compared with Pd alone in patients with relapsed/refractory multiple myeloma who had received at least 1 prior line of therapy (HR, 0.63; 95% CI, 0.47-0.85; 2-sided P = .0018). The corresponding median progression-free survival in the groups were 12.4 months (95% CI 8.3-19.3) vs 6.9 months (5.5-9.3).

Similarly, the objective response rate with D-Pd (69%) was higher compared with the Pd group (46%; odds ratio, 2.68; 95% CI, 1.65-4.35; < .0001). Complete response rates for the daratumumab regimen were also reported to be superior vs Pd alone, at 24.5% vs 3.9%, respectively.

After a median follow-up of 16.9 months, 99 patients (33%) on the trial had died. The risk for death was decreased by 9% with D-Pd (HR, 0.91; 95% CI, 0.61-1.35); however, survival data were immature at the time of data collection and follow-up is ongoing.

The safety profile of D-Pd was consistent with its known profile, with common grade 3/4 adverse events (AEs) vs Pd including neutropenia (68% vs 51%, respectively), leukopenia (17% vs 5%), lymphopenia (12% vs 3%), febrile neutropenia (9% vs 3%), and pneumonia (13% vs 7%). Rates of study treatment discontinuation due to treatment-emergent AEs were similar for both arms (2% vs 3%, respectively). The most common reason for treatment discontinuation was progressive disease. The rate of infusion-related reaction rates with the subcutaneous formulation appeared low (grade 1/2, 6%), and only 2% of patients had a local injection site reaction.

“We are delighted that Janssen received this FDA approval for Darzalex Faspro, making it the first and only FDA-approved subcutaneous anti-CD38 monoclonal antibody therapy available in this combination,” Helen Torley, president and chief executive officer at Halozyme, stated. “This introduces a new delivery option for multiple myeloma patients in the U.S. being treated with this 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 Pharmaceutical Companies of Johnson & Johnson. July 12, 2021. Accessed July 12, 2021. https://yhoo.it/3e8R1ts

2. Halozyme announces Janssen receives 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. Halozyne Therapeutics. July 12, 2021. Accessed July 12, 2021. https://bit.ly/3wJFHKN

3. Dimopoulos 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

4. Dimopoulos MA, Terpos E, Boccadoro M, et al. Apollo: Phase 3 randomized study of subcutaneous daratumumab plus pomalidomide and dexamethasone (D-Pd) versus pomalidomide and dexamethasone (Pd) alone in patients (Pts) with relapsed/refractory multiple myeloma (RRMM). Presented at: 2021 ASH Annual Meeting; December 4, 2020. Abstract 412.