On December 7, 2020 The Janssen Pharmaceutical Companies of Johnson & Johnson reported new data from the randomised Phase 2 GRIFFIN study showing that the addition of DARZALEX▼ (daratumumab) to lenalidomide, bortezomib and dexamethasone (D-RVd), followed by daratumumab plus lenalidomide (D-R) maintenance therapy, resulted in deeper and improved responses, including minimal residual disease (MRD) negativity, compared to RVd followed by R alone, in newly diagnosed, stem cell transplant-eligible patients with multiple myeloma (Press release, Janssen Pharmaceuticals, DEC 7, 2020, View Source [SID1234572372]).1 These data investigating the use of daratumumab in combination with RVd, which were shared in separate oral and poster presentations at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2020 Annual Meeting, provide further evidence that this regimen may provide greater efficacy for transplant-eligible, newly diagnosed multiple myeloma (NDMM) patients than standard therapy. This morning’s oral presentation (Abstract #549) shared longer-term follow-up data, and the poster presentation (Abstract #3243) featured additional data from the safety run-in cohort.1,2

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"The long-term GRIFFIN data show that maintenance therapy with daratumumab in combination with lenalidomide (D-R) resulted in deeper and longer responses compared to R alone in patients with multiple myeloma who are newly diagnosed and transplant-eligible," said Peter Voorhees, M.D.,* Atrium Health’s Levine Cancer Institute and GRIFFIN study investigator. "These data indicate that the addition of daratumumab to RVd followed by R maintenance results in improved response rates and depth of response during induction, consolidation and maintenance treatment cycles."

Key Findings from GRIFFIN (Abstract #549):
The GRIFFIN oral presentation featured updated safety and efficacy data based on longer follow-up for D-RVd and evaluated the potential role of D-R for maintenance therapy in patients with NDMM.1

Initial findings of GRIFFIN:
At the end of post-transplant consolidation (median follow-up, 13.5 months) in the response-evaluable population, the stringent complete response (sCR) rate favoured D-RVd vs. RVd (42.4 percent vs. 32.0 percent, P=0.0253).1
The complete response (CR) or better rate also favoured D-RVd vs. RVd (51.5 percent vs. 42.3 percent; P=0.0014).1
No new safety concerns were observed in the D-RVd arm receiving D-R maintenance therapy.1
The most common Grade 3/4 treatment-emergent adverse events (TEAEs) in the D-RVd arm receiving D-R maintenance therapy were neutropenia (43 percent), lymphopenia (23 percent), leukopenia (16 percent) and thrombocytopenia (15 percent).1
With an additional 12 months of D-R or R maintenance therapy (median follow up of 27.4 months), responses continued to deepen and remained higher for the daratumumab-containing arm.1
At the clinical cutoff date, the sCR rate favoured the daratumumab-containing arm (63.6 percent vs. 47.4 percent; P=0.0253).1
The CR or better rate continued to favour D-RVd vs. RVd (81.8 percent vs. 60.8 percent; P=0.0014).1
MRD negativity favoured D-RVd vs. RVd (62.5 percent vs. 27.2 percent, P=0.0001).1
No new safety concerns were observed with the D-R maintenance therapy.1
The 24-month progression-free survival (PFS) rate was 94.5 percent for D-RVd and 90.8 percent for RVd.1
Key Findings from GRIFFIN (Abstract #3243):
The poster presentation shared final results of the safety run-in cohort (n=16 patients) of the GRIFFIN study. These additional data showed that maintenance therapy with daratumumab and lenalidomide (D-R) improved both the sCR rate and MRD negativity rate in patients with NDMM who underwent D-RVd induction, autologous stem cell transplant (ASCT) and D-RVd consolidation. This deepening of responses was associated with durable remissions, and no new safety signals were observed with maintenance therapy.2

Initial findings from the safety run-in cohort for GRIFFIN:
By the end of post-transplant consolidation, the sCR rate was 56 percent.2
MRD negativity (10-5) at the end of consolidation was observed in 50 percent of patients, and no patients were MRD negative at 10-6.2
New findings:
The sCR rate improved to 94 percent by the end of both 12 and 24 months of D-R maintenance therapy.2
By the end of 24 months of D-R maintenance therapy, 81 percent of patients were MRD negative at 10-5, with five patients (31 percent) MRD negative at 10-6.2
At a median follow-up of 40.8 months, three of 16 patients had progressed, with estimated 24-month and 36-month PFS rates of 94 percent and 78 percent, respectively.2
With longer follow-up including two years of D-R maintenance therapy, no new safety concerns were identified.2
"The stringent complete response and minimal residual disease negativity rates with daratumumab combination maintenance therapy for transplant-eligible patients further solidify daratumumab as a foundational treatment for multiple myeloma," said Dr Catherine Taylor, Vice President, Medical Affairs Therapeutic Area Strategy, Europe, Middle East and Africa (EMEA), Janssen-Cilag Ltd., Middle East. "At Janssen, we remain focused on pursuing effective treatment combinations and investigating different endpoints, such as minimal residual disease, in order to provide effective treatments to patients across the spectrum of multiple myeloma."

"We continue to be encouraged by the GRIFFIN data showing deeper and improved responses in patients with newly diagnosed, ASCT-eligible multiple myeloma," said Andree Amelsberg, M.D., MBA, Vice President, U.S. Medical Affairs, Oncology Medical Affairs, Janssen Scientific Affairs, LLC. "These data show promising results for patients with newly diagnosed multiple myeloma and we remain committed to exploring the full potential of daratumumab and daratumumab subcutaneous formulation."

*Peter Voorhees is lead investigator of the GRIFFIN study and was not compensated for any media work.

#ENDS#

About the GRIFFIN Study3
The Phase 2 GRIFFIN (NCT02874742) study has enrolled and treated more than 200 adults ages 18-70 years with NDMM and who are eligible for high-dose therapy/autologous stem cell therapy (ASCT).

In the safety run-in cohort, patients received 25 mg of lenalidomide orally on Days 1-14; 1.3 mg/m2 of bortezomib subcutaneously on Days 1, 4, 8 and 11; and 20 mg of dexamethasone on Days 1, 2, 8, 9, 15 and 16, every 21 days during the induction and consolidation phases (Cycles 1-6). Daratumumab 16 mg/kg IV was given on Days 1, 8 and 15 of Cycles 1-4 and on Day 1 of Cycles 5-6.

During maintenance phase (Cycles 7-32), patients received 10 mg daily of lenalidomide (15 mg beginning at Cycle 10 if tolerated) on Days 1-21 every 28 days and daratumumab 16 mg/kg IV every 56 days; this was amended to every 28 days based upon emerging clinical pharmacokinetic data demonstrating improved target saturation with every 4-week maintenance dosing. Maintenance therapy with lenalidomide may be continued beyond Cycle 32 in both arms, per local standard of care.

In the subsequent randomised Phase 2 portion of the study, approximately 200 patients were randomised and received treatment with RVd, induction and consolidation, ASCT and maintenance therapy with lenalidomide; or daratumumab and RVd, ASCT and maintenance therapy with daratumumab and lenalidomide.

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 154,000 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 Additional studies are underway 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 and AL amyloidosis.15,16

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