J&J, Legend strengthen Carvykti's lead in early multiple myeloma with strong survival results

Johnson & Johnson and Legend Biotech's Carvykti has displayed significant potential in extending the lives of multiple myeloma patients, outperforming two standard-of-care triplet combinations. Following its strong performance in early treatment settings, Carvykti has further demonstrated life extension benefits. According to an update from the phase 3 CARTITUDE-4 trial, a single dose of Carvykti significantly reduced the risk of death by 45% compared to conventional combination treatments in patients who had undergone at least one prior therapy.

The trial compared Carvykti against combinations of Bristol Myers Squibb’s Pomalyst, Takeda’s Velcade, and dexamethasone (PVd), as well as J&J’s Darzalex, Pomalyst, and dexamethasone (DPd). While neither group reached its median overall survival time, 76.4% of patients in the Carvykti group were estimated to be alive at 30 months, compared to 63.8% in the control group. The data, presented at the 2024 International Myeloma Society (IMS) annual meeting, comes after a median patient follow-up of 33.6 months.

Earlier data from the study linked Carvykti to a 59% lower risk of disease progression or death, which facilitated its second-line FDA approval in April. Despite the FDA's warning about a higher risk of early death with Carvykti, the therapy's long-term benefits in extending life expectancy are evident. The survival curves for Carvykti improved around month 12 and continued to show a significant advantage thereafter. By about month 31, Carvykti’s survival curve had plateaued, indicating minimal subsequent deaths, while the control group continued to see declines.

Additionally, the trial assessed patients' quality of life. Despite worse baseline health metrics such as physical and social functioning, pain, and fatigue, patients in the Carvykti arm reported improved overall health over time, unlike those in the standard-of-care arm. Dr. Rahul Banerjee from Fred Hutchinson Cancer Center highlighted the significant improvements in patient-reported outcomes like pain and fatigue in the Carvykti group.

Carvykti's success in overall survival sets it apart from Bristol Myers Squibb and 2seventy bio's competing CAR-T therapy, Abecma, which did not demonstrate life extension benefits in the KarMMa-3 trial. However, Abecma may still be relevant in the myeloma market. At the IMS meeting, Dr. Doris Hansen from Moffitt Cancer Center presented a retrospective study comparing Carvykti and Abecma in previously treated myeloma patients. The study involved 641 real-world patients, of whom 586 received either BCMA CAR-T product.

The analysis indicated that Carvykti had better efficacy, reducing the risk of progression or death by 56% compared to Abecma in the intent-to-treat population and 53% in those who were infused. Carvykti also showed a favorable overall survival rate. However, it was associated with higher rates of severe toxicities, including a 5.5-fold increase in severe cytokine release syndrome and a 21-fold increase in delayed neurotoxicity compared to Abecma.

Dr. Banerjee noted the increased efficacy and specific adverse events with Carvykti, suggesting that these findings will help physicians choose between the two treatments based on patient characteristics. Carvykti, perceived as the more effective BCMA CAR-T therapy, is gaining market share over Abecma. In a further setback for Abecma, BMS and 2seventy recently decided to halt the phase 3 KarMMa-9 trial, which was testing Abecma as a first-line maintenance treatment for newly diagnosed multiple myeloma patients with suboptimal stem cell transplant responses.

Meanwhile, Carvykti's first-line studies are progressing, with CARTITUDE-5 having completed enrollment and CARTITUDE-6 expected to be fully enrolled next year.

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