DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj)-based regimens demonstrate improved rates of minimal residual disease (MRD) negativity and progression-free survival in patients with newly diagnosed multiple myeloma

New analysis from Phase 3 CEPHEUS study demonstrates 85 percent of patients who achieved MRD negativity (10-6) with DARZALEX FASPRO® were progression free at 4.5 years

Subgroup analysis from Phase 3 AURIGA study show higher rates of MRD-negative conversion in patient populations disproportionately impacted by multiple myeloma

December 8, 2024

SAN DIEGO, Dec. 8, 2024 - Johnson & Johnson (NYSE: JNJ) today announced data highlighting that DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj)-based regimens improve overall and sustained minimal residual disease (MRD) negativity rates and progression-free survival (PFS) in patients with newly diagnosed multiple myeloma (NDMM), regardless of transplant status. These findings were demonstrated in an expanded MRD analysis of the Phase 3 CEPHEUS study (Abstract #362) and a post hoc analysis of clinically relevant subgroups in the Phase 3 AURIGA study (Abstract #675), which were both featured as oral presentations at the 2024 American Society of Hematology (ASH) Annual Meeting.

Data from the expanded MRD analysis of the Phase 3 CEPHEUS study show the addition of DARZALEX FASPRO® to bortezomib, lenalidomide and dexamethasone (D-VRd) leads to improved and deepened rates of overall and sustained MRD negativity (both 10-5 and 10-6 sensitivity thresholds in patients who achieved a complete response or better) versus VRd alone, and shows significantly improved progression-free survival.1 CEPHEUS is the fifth Phase 3 study showing the addition of DARZALEX® improves depth and duration of response, leading to improved progression-free survival.

At a median follow-up of 58.7 months, overall MRD-negativity rates were significantly higher with D-VRd versus VRd at both 10–5 (60.9 percent vs. 39.4 percent; odds ratio [OR], 2.37; 95 percent confidence interval [CI], 1.58-3.55; P<0.0001) and 10–6 (46.2 percent vs. 27.3 percent; OR, 2.24; 95 percent CI, 1.48-3.40; P=0.0001) sensitivity thresholds. Treatment with D-VRd shows continued benefit of sustained MRD negativity for two years (10-5: 42.1 percent vs. 22.7 percent; 10-6: 27.9 percent vs. 13.6 percent). Additionally, the deeper and more sustained MRD negativity rates with D-VRd trended with improved progression-free survival (PFS) rates – the estimated 54-month PFS rates were 86.2 percent for D-VRd patients versus 79 percent for VRd in MRD negative (10-6) patients, and 51 percent versus 36.5 percent for MRD-positive patients.

“This analysis from the CEPHEUS study comparing daratumumab-VRd versus VRd, showed higher rates of both overall and sustained MRD negativity alongside promising trends in progression-free survival,” said Sonja Zweegman, MD, PhD, head of the Department of Hematology, Amsterdam University Medical Center.* “This regimen has the potential to improve outcomes for patients with newly diagnosed multiple myeloma who are ineligible for transplant or for whom transplant is not planned as initial therapy.”

Addition of DARZALEX FASPRO® to maintenance regimens resulted in higher MRD negativity rates across clinically relevant subgroups by age, race, disease stage and cytogenetic risk

In a post hoc analysis of the Phase 3 AURIGA study, an investigational maintenance regimen of DARZALEX FASPRO® combined with lenalidomide (R) resulted in consistently improved MRD-negative conversion rates after 12 months. These results were consistent across anti-CD38 naïve patient subgroups who were MRD-positive post-autologous stem cell transplant (ASCT). In patients older than 65 years, MRD-negative rates were higher when treated with D-R maintenance therapy compared to R alone (52.6 percent vs. 17.5 percent; OR, 5.24; 95 percent CI, 1.86-14.74). Maintenance therapy with D-R showed a consistently higher conversion to MRD negativity in Black patients (n=20) compared to R alone (60.0 percent vs 16.7 percent; OR, 7.50; 95 percent CI, 1.85-30.34) and white patients (n=67) (46.3 percent vs. 20.6 percent; OR, 3.32; 95 percent CI, 1.55-7.10).

Data also show that the investigational maintenance regimen of D-R resulted in higher MRD-negative conversion rates for patients with advanced-stage disease (Stage III) as defined by the International Staging System (ISS) (65.2 percent vs. 13 percent; OR, 12.50; 95 percent CI, 2.83-55.25) and patients with high cytogenetic risk per the standard definition (31.8 percent vs. 6.7 percent; OR, 6.53; 95% CI, 0.71-60.05) or the revised definition (43.8 percent vs. 13.3 percent; OR, 5.06; 95 percent CI, 1.43-17.88).

“Patients over 65, Black individuals, and those with advanced or high-risk disease are disproportionately impacted by multiple myeloma and historically have had fewer treatment options that yield deep and durable results,” said Imran Khan, M.D., Ph.D., Vice President, Medical Affairs, Hematology, Johnson & Johnson Innovative Medicine. “Evaluating MRD negativity in these patients underlies its importance as a recognized predictor of long-term progression-free survival. The data being presented at ASH this year emphasize the potential of DARZALEX FASPRO in helping newly diagnosed patients achieve MRD negativity.”

Final analysis of Phase 3 ANDROMEDA study reinforces DARZALEX FASPRO®-based regimen showing significant overall survival in patients with newly diagnosed light chain (AL) amyloidosis

The final analysis of the Phase 3 ANDROMEDA study was also presented (Abstract #891), showing that the addition of DARZALEX FASPRO® to bortezomib, cyclophosphamide, and dexamethasone (D-VCd) demonstrated deeper and more rapid hematologic responses, resulting in a statistically significant improvement in both OS and major organ deterioration progression-free survival (MOD-PFS) (i.e., end-stage renal or cardiac disease, hematologic progression, or death) for patients with newly diagnosed AL amyloidosis, a rare plasma cell disorder associated with the deterioration of vital organs. Patients treated with D-VCd showed a 56 percent reduction in the risk of progression or death (hazard ratio [HR] = 0.44, P< 0.0001). The median MOD-PFS was not reached for D-VCd, while it was 30.2 months for VCd. Additionally, D-VCd also provided significant survival benefits with a HR of 0.62 (P=0.0121), indicating a 38 percent reduction in the risk of death compared to VCd. The 5-year survival rate was 76.1 percent for D-VCd versus 64.7 percent for VCd.

In the CEPHEUS, AURIGA and ANDROMEDA studies, the safety profiles were consistent with the known safety profile for DARZALEX FASPRO®.

About the CEPHEUS Study
CEPHEUS (NCT03652064) is an ongoing, multicenter, randomized, open-label, Phase 3 study comparing the efficacy and safety of D-VRd vs VRd in patients with newly diagnosed multiple myeloma who are transplant-ineligible or for whom transplant is not intended as initial therapy. Primary endpoint is MRD negativity rate at 10-5 sensitivity threshold. Secondary endpoints include PFS, MRD-negative rate at one year, durable MRD negativity, ORR, time to and duration of response, PFS on next line of therapy, overall survival and safety. The trial has enrolled 396 patients in 13 countries.

About the AURIGA Study
The randomized study (NCT03901963) included 200 patients aged 18-79 years with newly diagnosed multiple myeloma who are minimal residual disease (MRD)-positive after frontline autologous stem cell transplant. Patients received investigational 1,800 milligram (mg) daratumumab by subcutaneous (SC) injection in combination with lenalidomide (orally) as maintenance therapy for a maximum of 36 cycles. Each cycle is 28 days. Patients in the comparative arm will receive lenalidomide (orally) alone as maintenance therapy for a maximum of 36 cycles. Each cycle is 28 days.

About the ANDROMEDA Study
ANDROMEDA (NCT03201965) is an ongoing Phase 3, randomized, open-label study investigating the safety and efficacy of DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) in combination with bortezomib, cyclophosphamide and dexamethasone (D-VCd), compared to VCd alone, for the treatment of adult patients with newly diagnosed light chain (AL) amyloidosis. The study includes 388 patients with newly diagnosed AL amyloidosis with measurable hematologic disease and one or more organs affected. The primary endpoint is overall complete hematologic response rate by intent-to-treat (ITT). Patients received DARZALEX FASPRO® 1,800 mg/30,000 units administered subcutaneously once weekly from weeks one to eight, once every two weeks from weeks nine to 24 and once every four weeks starting with week 25 until disease progression or unacceptable toxicity or a maximum of two years. Among patients who received D-VCd, 74 percent were exposed for 6 months or longer and 32 percent were exposed for greater than one year.

About Multiple Myeloma
Multiple myeloma is a blood cancer that affects a type of white blood cell called plasma cells, which are found in the bone marrow.7 In multiple myeloma, these malignant plasma cells proliferate and replace normal cells in the bone marrow.8 Multiple myeloma is the second most common blood cancer worldwide and remains an incurable disease.9 In 2024, it is estimated that more than 35,000 people will be diagnosed with multiple myeloma in the U.S. and more than 12,000 will die from the disease.10 People with multiple myeloma have a 5-year survival rate of 59.8 percent. While some people diagnosed with multiple myeloma initially have no symptoms, most patients are diagnosed due to symptoms that can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels, kidney problems or infections.

About AL Amyloidosis
Light chain (AL) amyloidosis is a rare and potentially fatal hematologic disorder that can affect the function of multiple organs. The disease occurs when bone marrow produces abnormal pieces of antibodies called light chains, which clump together to form a substance called amyloid. These clumps of amyloid are deposited in tissues and vital organs and interfere with normal organ function, eventually causing organ deterioration.13,14 It is the most common type of amyloidosis. AL amyloidosis frequently affects the heart, kidneys, digestive tract, liver and nervous system, and is potentially fatal if left untreated.15 Diagnosis is often delayed and prognosis is poor due to advanced, multi-organ, particularly cardiac, involvement.16,17 Each year, an estimated 4,500 people develop AL amyloidosis in the U.S. alone.

About DARZALEX FASPRO® and DARZALEX®
DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) received U.S. FDA approval in May 2020 and is approved for eight indications in multiple myeloma, three of which are for frontline treatment in newly diagnosed patients who are transplant eligible or ineligible.14 It is the only subcutaneous CD38-directed antibody approved to treat patients with MM. DARZALEX FASPRO® is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme’s ENHANZE® drug delivery technology.

DARZALEX® (daratumumab) received U.S. FDA approval in November 2015 and is approved in eight indications, three of which are in the frontline setting, including newly diagnosed patients who are transplant eligible and ineligible.

DARZALEX® is the first CD38-directed antibody approved to treat multiple myeloma.6 DARZALEX®-based regimens have been used in the treatment of more than 580,000 patients worldwide and more than 239,000 patients in the U.S. alone.

In August 2012, Janssen Biotech, Inc. and Genmab A/S entered a worldwide agreement, which granted Janssen an exclusive license to develop, manufacture and commercialize daratumumab.

Since 2020, the National Comprehensive Cancer Network® (NCCN®) has recommended daratumumab-based combination regimens for the treatment of newly diagnosed multiple myeloma and relapsed and refractory multiple myeloma.† For newly diagnosed multiple myeloma in non-transplant candidates, the NCCN® guidelines recommend daratumumab in combination with lenalidomide and dexamethasone as a Category 1 preferred regimen; daratumumab in combination with bortezomib, melphalan, and prednisone as another recommended Category 1 regimen; and daratumumab in combination with bortezomib, cyclophosphamide, and prednisone as another recommended Category 2A regimen. For newly diagnosed multiple myeloma in transplant candidates, the NCCN® guidelines recommend daratumumab in combination with bortezomib, lenalidomide and dexamethasone as another recommended Category 2A regimen; daratumumab in combination with bortezomib, thalidomide and dexamethasone as a Category 2A regimen useful in certain circumstances; daratumumab in combination with carfilzomib, lenalidomide and dexamethasone as a Category 2A regimen useful in certain circumstances; and daratumumab in combination with cyclophosphamide, bortezomib and dexamethasone as a Category 2A regimen useful in certain circumstances. For maintenance in transplant candidates, the NCCN guidelines recommend daratumumab in combination with lenalidomide as useful in certain circumstances. In relapsed/refractory myeloma, four daratumumab regimens are listed as Category 1 preferred regimens for early relapses (1-3 prior therapies): daratumumab in combination with lenalidomide and dexamethasone; daratumumab in combination with bortezomib and dexamethasone; daratumumab in combination with carfilzomib and dexamethasone; and daratumumab in combination with pomalidomide and dexamethasone [after one prior therapy including lenalidomide and a proteasome inhibitor (PI)]. The NCCN® also recommends daratumumab in combination with cyclophosphamide, bortezomib and dexamethasone as another Category 2A regimen for early relapses (1-3 prior therapies) and as monotherapy as a Category 2A regimen useful in certain circumstances for early relapse patients after at least three prior therapies, including a PI and an immunomodulatory agent, or for patients who are double refractory to a PI and an immunomodulatory agent.