The prevailing treatment paradigm for newly diagnosed multiple myeloma (NDMM) patients who have received autologous stem cell transplantation (SCT) primarily consists of chemotherapy or Johnson & Johnson’s (J&J) Darzalex in combination with chemotherapy. The GRIFFIN study analysed 207 NDMM transplant-eligible patients receiving the lenalidomide, bortezomib, and dexamethasone (RVd) combination against Darzalex and RVd (D-RVd). A strong indicator of patient response to treatment is the minimal residual disease (MRD) negativity metric, which was much higher with the D-RVd combination when compared to the RVd group (64.4% versus 30.1%). With a 36-month follow-up, the estimated progression-free survival (PFS) of patients receiving D-RVd was 78.1%.
While D-RVd has been a mainstay treatment within the National Comprehensive Cancer Network’s recommendations for treating NDMM patients, there have been recent developments in the field brought about by bispecific T-cell engagers (BiTEs). Johnson & Johnson has seen the approval of both Tecvayli and Talvey for the treatment of relapsed/refractory multiple myeloma (RRMM), in 2022 and 2023, respectively. The utility of these BiTEs comes from their ability to target two receptor sites – in the case of Tecvayli, cluster of differentiation 3 and B-cell maturation antigen. This mechanism yields strong specificity and immune response directed towards multiple myeloma (MM) cells, producing good MRD-negativity and PFS results. The MajesTEC-1 trial demonstrated that of the 165 RRMM patients receiving Tecvayli, 46% had achieved an MRD-negativity, and the PFS reached 11.3 months. One of the key difficulties in treating RRMM is relatively poor performance status, compared to the earlier disease state. Tecvayli is associated with a myriad of immune-mediated side effects such as cytokine release syndrome, that occurred in 72.1% of patients in the MajesTEC-1 trial. The median duration of treatment with Tecvayli was 8.5 months, which is relatively shorter compared to more traditional chemotherapy regimens. While the overall results of the MajesTEC-1 trial were positive, the question of how well this performance would translate to earlier lines of therapy remained. Results of the MajesTEC-4 trial presented at the ASH Annual Meeting on 8 December showed how Tecvayli could be an up-and-coming therapy option in the landscape for NDMM patients receiving autologous SCT. The Phase III trial saw three different doses of Tecvayli and lenalidomide used in 94 patients. All patients receiving Tecvayli and lenalidomide demonstrated MRD-negativity, indicating the lack of disease progression at the follow-up. Patients receiving dosing every four weeks had a 40% cumulative incidence of grade 3-4 neutropenia by six months while patients with a ‘step-up’ dosing once every week to once every four weeks had over double the incidence (81.3%). The clinical data demonstrates that Tecvayli plus lenalidomide has potent and durable action in MM, and while there are some significant immune-related adverse events, these issues could be fine-tuned with a modified dosing regimen.
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Johnson & Johnson’s Carvykti has also seen recent approval in MM for second-line use. Carvykti’s clinical efficacy in NDMM patients is being assessed in the CARTITUDE-6 study, with an estimated completion date of mid-2033. Leading data and analytics company GlobalData’s patient-based forecast predicts Tecvayli will reach a peak of $2.1bn in sales globally by 2030 in MM while Carvykti is expected to reach $6.2bn in the same year. Johnson & Johnson’s diverse portfolio in BiTEs and chimeric antigen receptor T-cell therapies is positioned to pay off in the short and long term, dominating a large segment of the early and late MM patient share for years to come.
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