Multiple myeloma remains an incurable blood cancer, with nearly all patients relapsing and requiring subsequent therapy
Johnson & Johnson Innovative Medicine announced today that TALVEY®▼ (talquetamab) has been approved for reimbursement in Ireland as a monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma (RRMM) who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody and have demonstrated disease progression on the last therapy.
The announcement follows conditional marketing authorisation (CMA) in 2023 which was supported by positive results from the Phase 1/2 MonumenTAL-1 study evaluating the safety and efficacy of talquetamab in patients with RRMM.1
Multiple myeloma remains an incurable blood cancer, with nearly all patients relapsing and requiring subsequent therapy.2,3 As the disease progresses, relapses for patients become more aggressive with each new line of therapy, and remissions become progressively shorter.
Approximately, 380 people are diagnosed with multiple myeloma each year in Ireland.4 While Irish figures show that the five-year net survival for someone diagnosed with MM has increased from 30 per cent in the mid-1990s to 60 per cent by 2020, the unmet need for those with RRMM remains.5
Talquetamab is a bispecific T-cell engaging antibody that binds to CD3, on the surface of T-cells, and G protein-coupled receptor class C group 5 member D (GPRC5D), a novel target expressed on the surface of multiple myeloma cells and hard keratinised tissues, with minimal to no expression detected on B-cells and B-cell precursors.6 Talquetamab is approved as a weekly (QW) or biweekly (Q2W) subcutaneous (SC) injection, after an initial step-up phase.6
Dr Janusz Krawczyk, Consultant Haematologist at Galway University Hospital said: “The treatment landscape for multiple myeloma demands continuous innovation. The reimbursement of talquetamab is a positive development for people living with relapsed and refractory disease, a cohort who have gone through complex treatment and experience challenging outcomes. Talquetamab’s novel mechanism, engaging the GPRC5D target, offers a distinct therapeutic approach for advanced disease. We are encouraged by its ability to induce deep responses, even in those who have undergone extensive prior treatments, underscoring its potential to truly make a difference in this hard-to-treat blood cancer.”
Michaela Hagenhofer, General Manager, Commercial Operations at Johnson & Johnson Innovative Medicine said: “The reimbursement of talquetamab in Ireland marks a key milestone in J&J’s commitment to advancing multiple myeloma care. This innovative therapy, now accessible to Irish patients, provides clinicians additional options for advanced disease. With over two decades of research, we are committed to improving outcomes through a portfolio of immunotherapies that can be used as monotherapy or in combination at various disease stages. We are proud that talquetamab is manufactured at our biopharmaceutical facility in Ringaskiddy, Co Cork, which also supplied clinical trial stock for its development and approval.”
Patients in the Phase 1/2 MonumenTAL-1 study (0.8 mg/kg Q2W: n=145; 0.4 mg/kg QW: n=143) had received a median of five (range, 2-17) prior lines of therapy and showed meaningful overall response rates (ORR) across both doses.1
With a median follow-up of 12.7 months, 71.7 per cent (95 percent Confidence Interval [CI], 63.7-78.9) of response-evaluable patients treated at the 0.8 mg/kg Q2W dose achieved a response, 60.8 per cent achieved a very good partial response (VGPR) or better and 38.7 percent achieved a complete response (CR) or better.1 With a median follow-up of 18.8 months, 74.1 per cent (95 per cent CI, 66.1-81.1) of response-evaluable patients treated with the 0.4 mg/kg QW dose achieved a response, 59.5 per cent achieved a VGPR or better and 33.6 percent achieved a CR or better.1 Responses were durable with a median duration of response not reached (95 per cent CI, 13-Not Estimable [NE]) in the 0.8 mg/kg Q2W dose group and 9.5 months (95 percent CI, 6.7-13.3) in the 0.4 mg/kg QW dose group.1 An estimated 76.3 per cent and 51.5 per cent of patients maintained a response for at least nine months at the 0.8 mg/kg Q2W and 0.4 mg/kg QW doses, respectively.1
The MonumenTAL-1 study also included 51 patients with prior T-cell redirection therapy.1 Patients had received a median of five (3-15) prior lines of therapy, including prior exposure to a bispecific antibody (35.3 per cent), CAR-T cell therapy (70.6 per cent) or both (six percent).1 With a median duration of follow-up of 14.8 months, 64.7 per cent of patients achieved a response, 54.9 per cent achieved a VGPR or better and 35.3 per cent achieved a CR or better.1 Median duration of response was 11.9 months (95 per cent CI, 4.8-NE) and the 12-month overall survival rate was 62.9 per cent.1
The most common adverse events (AEs) observed in the study were cytokine release syndrome (CRS; 77 per cent, 1.5 per cent Grade 3 or 4), dysgeusia (72 per cent, all Grade 1 or 2), hypogammaglobulinaemia (67 per cent, all Grade 1 or 2) and nail disorders (56 per cent, all Grade 1 or 2).1 In addition, 40 per cent of patients experienced weight loss, including 3.2 per cent with Grade 3 or 4 weight loss.1 The most common infections were upper respiratory tract infection (29 percent, 2.1 per cent Grade 3 or 4) and COVID-19 (19 per cent, 2.9 per cent Grade 3 or 4).1 Neurologic toxicities were reported in 29 per cent of patients, including immune effector cell-associated neurotoxicity syndrome (ICANS; 10 per cent, 2.3 per cent Grade 3 or 4).1 Adverse reactions leading to treatment discontinuation were mainly due to ICANS (1.1 per cent) and weight loss (0.9 pe rcent).1
References available upon request.
