89% MRD Negativity Rate: Johnson & Johnson’s CARVYKTI® Advances Toward Blockbuster Status in Multiple Myeloma
Johnson & Johnson
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December 10, 2024 (GLOBE NEWSWIRE) -- Johnson & Johnson's international companyOral Presentation at the 2024 American Society of Hematology (ASH) Annual Meeting in San Diego, California, USANew results from the Phase 3 CARTITUDE-4 study announced, showing a single infusionCARVYKTI®(Ciltacabtagene autoleucel; cilta-cel) significantly improved the MRD-negative rate (10-5) in patients with relapsed or refractory multiple myeloma (RRMM) who are lenalidomide-resistant and received one to three prior lines of therapy, including a proteasome inhibitor (PI), compared to standard regimens of pomalidomide, bortezomib, and dexamethasone (PVd) or daratumumab, pomalidomide, and dexamethasone (DPd). MRD is a prognostic marker for long-term survival outcomes in patients with multiple myeloma. These results add to the OS benefits presented earlier this year at the International Myeloma Society meeting as the first cell therapy to demonstrate a significant extension in OS in patients with multiple myeloma compared to standard therapies.
The Collaborative Drug of Legend Biotech and Johnson & JohnsonCARVYKTI®（ciltacabtagene autoleucel；Cilta-cel) Since its debut, the sales in 2024 have exceeded 600 million US dollars and it is expected to become a blockbuster drug with sales of over 1 billion US dollars.
"MRD data further emphasizes the benefits of using CARVYKTI for treatment," said Yi Lin, M.D., a hematologist and oncologist at Mayo Clinic in Rochester, Minnesota."These new findings support CARVYKTI as a transformative treatment option, leading to improvements in progression-free survival, overall survival, and now minimal residual disease negativity."”
"Cilta-cel has already demonstrated a significant impact on overall survival and progression-free survival compared to standard therapies," said Rakesh Popat, MD, from University College London Hospitals NHS Foundation Trust, London, UK, and the primary study investigator. "MRD-negative results indicate that patients with multiple myeloma treated with cilta-cel have deeper responses compared to standard therapies, further emphasizing the benefits of cilta-cel as an early second-line single infusion."
Phase 3 CARTITUDE-4 Study Evaluates Cilta-cel Versus PVd or DPd Standard Therapy in RRMM Patients Who Have Received at Least One Prior Line of Therapy.Patients who received one to three lines of therapy, including proteasome inhibitors (PI) and immunomodulatory drugs (IMiD), and were refractory to lenalidomide, were randomly assigned (cilta-cel, n=208; standard therapy, n=211).In the median follow-up of nearly three years (34 months), the MRD negativity rate in evaluable patients was more than double in the cilta-cel treatment group compared to the standard therapy group (89% vs. 38%; p<0.0001).At 2.5 years (30 months), the proportion of evaluable patients with sustained (12 months or longer) MRD-negative complete response or better was five times higher in the cilta-cel treatment group compared to the standard therapy group (52% vs. 10%; p<0.0001).A post-hoc comparison between CARTITUDE-4 and CARTITUDE-1 was also proposed, comparing earlier treatment (1-3 vs. 3+ prior lines of therapy), which showed higher MRD negativity rates, progression-free survival (PFS), and OS rates when cilta-cel was used earlier in the treatment.
"We are encouraged by these striking results of cilta-cel, as MRD negativity is a key prognostic marker for prolonging progression-free and overall survival, and should be the goal of every treatment," said Edmond Chan, MBChB, M.D. (Res), Hematology Therapeutic Area Lead, Innovative Medicine EMEA, Johnson & Johnson. "Cilta-cel reflects our commitment to transforming multiple myeloma care, with a single infusion offering the potential for deeper, more durable responses, which could redefine the treatment landscape for patients diagnosed with this complex disease."”
AboutCARVYKTI® (CILTA-CEL, Ciltacabtagene Autoleucel) ：
Ciltacabtagene Autoleucel is a chimeric antigen receptor T-cell (CAR-T) therapy targeting B-cell maturation antigen (BCMA). It modifies the patient's own T cells using a transgene encoding the chimeric antigen receptor (CAR) to recognize and eliminate BCMA-expressing cells. BCMA is primarily expressed on the surface of malignant multiple myeloma B cell lineages, late-stage B cells, and plasma cells. The CAR protein of Ciltacabtagene Autoleucel contains two single-domain antibodies targeting BCMA, exhibiting high affinity for BCMA-expressing cells. After binding to BCMA-expressing cells, the CAR promotes T-cell activation and expansion, leading to the elimination of target cells.
In December 2017, Janssen and Legend Biotech entered into a global exclusive license and collaboration agreement to develop and commercialize Ciltacabtagene Autoleucel. In February 2022, Ciltacabtagene Autoleucel was approved by the U.S. FDA for marketing, followed by a conditional marketing authorization granted by the EU EC in May, and approval from Japan's MHLW in September for the treatment of adult patients with relapsed or refractory multiple myeloma, under the brand name CARVYKTI.®Cilta-cel received Breakthrough Therapy Designation in the United States in December 2019 and in China in August 2020. Additionally, cilta-cel received PRIME (PRIority MEdicines) designation from the European Commission in April 2019. The U.S. FDA, European EMA, and Japan PMDA granted cilta-cel Orphan Drug Designation in February 2019, February 2020, and June 2020, respectively. In March 2022, the Committee for Orphan Medicinal Products of the European Medicines Agency unanimously recommended maintaining the orphan drug designation for cilta-cel based on clinical data showing improved and sustained complete response rates post-treatment.
AboutMultiple Myeloma ：
Multiple myeloma is considered an incurable hematologic malignancy caused by the excessive proliferation of plasma cells in the bone marrow.It is estimated that more than 35,000 people in the United States will be diagnosed with multiple myeloma and over 12,000 will die from the disease in 2024.Although some patients with multiple myeloma are asymptomatic and are diagnosed due to the emergence of symptoms, these symptoms may include bone disease, abnormal low blood cell counts, elevated blood calcium, kidney problems, or infections.
AboutCARTITUDE-4 ：
CARTITUDE-4 (NCT04181827) is an international, randomized, open-label Phase 3 study evaluating the efficacy and safety of ciltacabtagene autoleucel compared with pomalidomide, bortezomib, and dexamethasone (PVd) or daratumumab, pomalidomide, and dexamethasone (DPd) in adult patients with relapsed and lenalidomide-refractory multiple myeloma who have received one to three prior lines of therapy (including a PI and an IMiD).
References:
https://www.globenewswire.com/news-release/2024/12/10/2994233/0/en/CARVYKTI-ciltacabtagene-autoleucel-cilta-cel-demonstrated-significantly-higher-rates-of-minimal-residual-disease-negativity-compared-to-standard-therapies-in-the-CARTITUDE-4-study.html
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