On December 4, 2020 The Janssen Pharmaceutical Companies of Johnson & Johnson reported results of the Phase 3 APOLLO study showing that the addition of DARZALEX▼ (daratumumab) subcutaneous (SC) formulation to pomalidomide and dexamethasone (D-Pd) significantly reduced the risk of progression or death by 37 percent, compared to Pd alone in patients with multiple myeloma (MM) after the first or subsequent relapse of disease (Press release, Janssen Pharmaceuticals, DEC 4, 2020, View Source [SID1234572180]).1 The APOLLO results, which will be presented on Sunday, December 6 at 9:00 p.m. CET during the American Society of Hematology (ASH) (Free ASH Whitepaper) 2020 Annual Meeting and featured in the ASH (Free ASH Whitepaper) press briefing (Abstract #112), add to the body of evidence supporting treatment with daratumumab SC-based regimens for patients with relapsed MM.
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These data were the basis for recent regulatory submissions in Europe and the United States (U.S.) seeking approval for daratumumab SC in combination with Pd for the treatment of patients with relapsed or refractory MM, with two or more prior lines of therapy, including lenalidomide and a proteasome inhibitor (PI).2
"For patients with multiple myeloma who relapse, it is important that efficacious treatments significantly reduce the risk of progression. The data presented at ASH (Free ASH Whitepaper) makes D-Pd a compelling treatment option for early relapsed or lenalidomide refractory patients," said Meletios A. Dimopoulos, M.D.,* 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. "The APOLLO study also highlights the potential benefits of the subcutaneous formulation of daratumumab, which offers patients and physicians a three- to five-minute injection experience and the potential to reduce infusion-related reactions compared to intravenous administration of daratumumab."
Key Findings from the APOLLO Oral Presentation (Abstract #412):
The study met its primary endpoint of improved progression-free survival (PFS).1 When added to Pd, daratumumab SC significantly reduced the risk of progression or death by 37 percent, compared to Pd alone (hazard ratio, 0.63; 95 percent confidence interval, 0.47-0.85; P=0.0018).1 The median PFS for the D-Pd vs. Pd arms was 12.4 vs. 6.9 months, respectively.1
Response rates were significantly higher with D-Pd compared to Pd alone, including rates of overall response (69 percent vs. 46 percent), rates of very good partial response (VGPR) or better (51 percent vs. 20 percent), over six times the rate of complete response (CR) (25 percent vs. 4 percent) and over four times the rate of minimal residual disease-negativity (9 percent vs. 2 percent).1
The rate of infusion-related reactions with daratumumab SC was 5 percent (all Grade 1/2), and 2 percent of patients had local injection-site reactions (all Grade 1). Median duration of administration was five minutes.1 Both of these parameters are in line with what has previously been reported for daratumumab SC.
The rates of study treatment discontinuation due to treatment emergent adverse events were similar for D-Pd vs. Pd (2 percent vs. 3 percent).1
The safety profile of D-Pd is consistent with known profiles of daratumumab SC and Pd. The most common Grade 3/4 treatment-emergent adverse events (TEAEs) were neutropenia (68% vs. 51%), anaemia (17% vs. 21%), thrombocytopenia (17% vs. 18%), and leukopenia (17% vs. 5%). The most common serious TEAEs were pneumonia (13% vs. 7%) and lower respiratory tract infection (11% vs. 9%).1
"Despite much progress over the last decade, multiple myeloma remains a disease with considerable unmet need, with many patients progressing or relapsing on their initial treatment," said Dr Catherine Taylor, VP, Medical Affairs Therapeutic Area Strategy, Europe, Middle East and Africa (EMEA), Janssen-Cilag Ltd., Middle East. "At Janssen, we continually strive to address the complex needs of these patients and are devoted to pursuing new treatment formulations, such as daratumumab SC, as part of different treatment regimens."
"We are encouraged by the efficacy of this combination with daratumumab SC, which has improved outcomes over pomalidomide-dexamethasone, a widely used regimen for patients with relapsed or refractory myeloma who have received prior treatment with lenalidomide," said Craig Tendler, M.D., Vice President, Late Development and Global Medical Affairs, Janssen Research & Development, LLC. "Together with the reduced infusion time for patients receiving daratumumab SC as compared to the intravenous formulation, the APOLLO study results further solidify this differentiated anti-CD38 monoclonal antibody as a foundational treatment in multiple myeloma for patients who are in need of additional treatment options."
*Meletios A. Dimopoulos is lead investigator of the APOLLO study and was not compensated for any media work
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About the APOLLO Study3
APOLLO (NCT01960348) is an ongoing multicentre, Phase 3, randomised, open-label study comparing daratumumab SC, pomalidomide and low-dose dexamethasone with pomalidomide and low-dose dexamethasone alone in patients with relapsed or refractory multiple myeloma who have received at least one prior treatment regimen with both lenalidomide and a proteasome inhibitor and have demonstrated disease progression. The study, which was conducted in collaboration with the European Myeloma Network, enrolled 304 participants.
The primary endpoint is progression-free survival (PFS) between treatment arms. Secondary endpoints include rates of overall response rate (ORR), very good partial response (VGPR) or better, complete response (CR) or better and duration of response, among others. The study reinforces findings from the Phase 1b EQUULEUS (MMY1001) trial, which formed the grounds for U.S. Food and Drug Administration (FDA) approval of intravenous D-Pd in 2017 for the treatment of relapsed and refractory multiple myeloma. In November 2020, Janssen submitted regulatory applications to the U.S. FDA and European Medicines Agency (EMA) seeking approval of the combination of D-Pd for the treatment of patients with relapsed or refractory multiple myeloma with ≥2 prior lines of therapy, including lenalidomide and a PI.
About daratumumab and daratumumab SC
In August 2012, Janssen Biotech, Inc. and Genmab A/S entered a worldwide agreement, which granted Janssen an exclusive license to develop, manufacture and commercialise daratumumab. Since launch, it is estimated that more than 150,000 patients have been treated with daratumumab worldwide.4 Daratumumab is the only CD38-directed antibody approved to be given subcutaneously to treat patients with multiple myeloma. Daratumumab SC is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme’s ENHANZE drug delivery technology.5
CD38 is a surface protein that is highly expressed across multiple myeloma cells, regardless of the stage of disease. Daratumumab SC binds to CD38 and induces myeloma cell death through multiple immune-mediated mechanisms of action, including complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP), as well as through apoptosis, in which a series of molecular steps in a cell lead to its death.6
Data across nine Phase 3 clinical trials in multiple myeloma and light chain (AL) amyloidosis, in both the frontline and relapsed settings, have shown that daratumumab-based regimens resulted in significant improvement in progression-free survival and/or overall survival.7,8,9,10,11,12,13,14,15 Additional studies have been designed to assess the efficacy and safety of daratumumab SC in the treatment of other malignant and pre-malignant haematologic diseases in which CD38 is expressed, including smouldering myeloma.16
For further information on daratumumab, please see the Summary of Product Characteristics at View Source
About Multiple Myeloma
Multiple myeloma (MM) is an incurable blood cancer that starts in the bone marrow and is characterised by an excessive proliferation of plasma cells.17 In Europe, more than 48,200 people were diagnosed with MM in 2018, and more than 30,800 patients died.18 Around 50 percent of newly diagnosed patients do not reach five-year survival,19,20 and almost 29 percent of patients with multiple myeloma will die within one year of diagnosis.21
Although treatment may result in remission, unfortunately, patients will most likely relapse as there is currently no cure.22 Relapsed and refractory myeloma is defined as disease that is nonresponsive while on salvage therapy, or progresses within 60 days of last therapy in patients who have achieved minimal response (MR) or better at some point previously before then progressing in their disease course.23 While some patients with MM have no symptoms at all, others are diagnosed due to symptoms that can include bone problems, low blood counts, calcium elevation, kidney problems or infections.24 Patients who relapse after treatment with standard therapies, including proteasome inhibitors and immunomodulatory agents, have poor prognoses and require new therapies for continued disease control.25