FDA Approves Subcutaneous Daratumumab Plus Pd for Multiple Myeloma at First or Subsequent Relapse


The FDA has approved daratumumab plus hyaluronidase-fihj (Darzalex Faspro) plus pomalidomide and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least 1 prior line of therapy, including lenalidomide and a proteasome inhibitor



The FDA has approved daratumumab plus hyaluronidase-fihj (Darzalex Faspro) plus pomalidomide and dexamethasone (Pd) for the treatment of adult patients with multiple myeloma who have received at least 1 prior line of therapy, including lenalidomide (Revlimid) and a proteasome inhibitor.1

The regulatory decision was supported by data from the phase 3 APOLLO trial (NCT01960348), which showed that the combination regimen resulted in a significant reduction in the risk of progression or death compared with Pd alone in this patient population.2

The median progression-free survival (PFS) in the investigative arm was 12.4 months (95% CI, 8.3-19.3) vs 6.9 months (95% CI, 5.5-9.3) in the control arm (HR, 0.63; 95% CI, 0.47-0.85; P = .0018); this translated to a 37% reduction.

Additionally, the overall response rate (ORR) proved to be higher with the addition of daratumumab plus hyaluronidase-fihj to Pd vs Pd alone, at 69% (95% CI, 61%-76%) vs 46% (38%-55%), respectively. Complete response rates in the investigative and control arms were 25% vs 4%, respectively, and the very good partial response (VGPR) or better rates were 51% vs 20%, respectively.

More patients who received the subcutaneous daratumumab regimen experienced minimal residual disease (MRD) negativity vs those who received Pd alone, at 9% vs 2%, respectively.

“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 2 Department of Clinical Therapeutics at the National and Kapodistrian University of Athens School of Medicine, Athens, Greece, and principal investigator, stated 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 [IV] administration.”

In the multicenter, open-label phase 3 APOLLO trial, investigators compared the safety and efficacy of subcutaneous daratumumab plus Pd with Pd alone in patients with relapsed or refractory multiple myeloma.

To be eligible for enrollment patients needed to be at least 18 years of age, have relapsed or refractory multiple myeloma with measurable disease, an ECOG performance status of 0 to 2, and have received at least 1 prior line of therapy with both lenalidomide an a proteasome inhibitor, and who achieved a partial response or better to 1 or more prior lines of therapy. If they had only received 1 prior line of therapy, they had to be refractory to lenalidomide.

Participants were randomized 1:1 to receive subcutaneous daratumumab plus Pd (n = 151) or Pd alone (n = 161). Patients were stratified based on number of prior lines of treatment (1 vs 2 to 3 vs ≥4) and International Staging System disease stage during screening (I vs II vs III).

All study participants were given oral pomalidomide at a starting dose of 4 mg once daily on days 1 through 21 of each treatment cycle plus oral dexamethasone at a once-daily dose of 40 mg (20 mg for those aged 75 years or older) on days 1, 8, 15, and 22 of each cycle. The investigative arm received subcutaneous daratumumab at 1800 mg co-formulated with recombinant human hyaluronidase PH20 at 2000 U/mL or IV daratumumab at a weekly dose of 16 mg per kg of bodyweight for cycles 1 and 2; this was given biweekly during cycles 3 to 6, and every 4 weeks thereafter. Patients received treatment until progressive disease or intolerable toxicity.

The primary end point of the trial was PFS, and secondary end points comprised ORR, VGPR or better rate, CR or better rate, MRD negativity status, time to response, duration of response (DOR), time to next therapy, and safety.

The median age of patients was 67 years (range, 35-90), and 35% of 211 patients with available data were noted to have a high-risk cytogenetic profile. Participants had received a median of 2 (range, 1-5) prior lines of therapy.

The median duration of treatment was 11.5 months in the investigative arm and 6.6 months in the control arm. Ninety-five percent of 149 patients received the subcutaneous formulation of daratumumab and 5% of 149 patients received the IV version. Of those who received the IV formulation, 4 switched to subcutaneous daratumumab and 3 experienced progression on the IV formulation before switching was allowed per the protocol amendment.

Additional findings showed that the median time to first response to treatment was 1.0 month (95% CI, 1.0-1.1) in the investigative arm and 1.9 months (95% CI, 1.0-2.0) in the control arm. The median DOR had not yet been reached (95% CI, 15.2–not reached) and was 15.9 months (95% CI, 8.3-24.8) in the daratumumab arm and the Pd alone arm, respectively. At the time of the PFS analysis, the data for overall survival were immature.

Two percent of patients who received the daratumumab regimen permanently discontinued treatment because of an adverse effect (AE). No adverse reactions leading to permanent discontinuation occurred in more than 1 patient.

The most frequent adverse reactions reported in 20% or more of patients included fatigue, pneumonia, upper respiratory tract infection, and diarrhea. Serious AEs were reported in 50% of patients on the investigative arm. The most common serious AEs reported in over 5% of patients on the investigative arm included pneumonia (15%) and lower respiratory tract infection (12%). Fatal AEs were reported in 7% of those who received the daratumumab regimen.

“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,” Craig Tendler, MD, vice president of Late Development and Global Medical Affairs at Janssen Research & Development, LLC, stated in a press release. “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.”


  1. Janssen announces US 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. The Janssen Pharmaceutical Companies of Johnson & Johnson. July 12, 2021. Accessed July 12, 2021.
  2. 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
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