Evolving role of novel therapies in myeloma: T-cell engagers and antibody-drug conjugates
DOI:
https://doi.org/10.58931/cht.2023.2233Abstract
Multiple myeloma (MM) is a hematologic malignancy characterized by the proliferation of abnormal clonal plasma cells. This population of neoplastic plasma cells can subsequently cause damaging lytic lesions to the bones, kidney dysfunction, high levels of calcium in the blood, and anemia. MM is more prevalent in individuals over age 65 than in younger individuals; the median age at diagnosis is 69 years old. This malignancy is generally considered incurable. The five-year overall survival (OS) is estimated to be as high as 82% with the Revised International Staging System (R-ISS) for Stage I of the disease, and 40% with R-ISS Stage III of the disease. A large proportion of patients in the relapsed/refractory (R/R) setting are unable to achieve durable responses to treatment. There remains an unmet need for novel, highly effective and well-tolerated therapies in this patient population.
Treatment of myeloma patients has evolved in the past two decades with the introduction of novel therapies: the proteasome inhibitors (PIs) bortezomib, carfilzomib and ixazomib; the immunomodulatory imide drugs (IMiDs) thalidomide, lenalidomide and pomalidomide; and the anti-CD38 monoclonal antibodies (MoAb’s) daratumumab and isatuximab. All of these therapeutic agents have demonstrated improved outcomes in myeloma patients. Survival of myeloma patients continues to improve over time, particularly with the combination of novel first-line and subsequent agents, resulting in median OS of 8 to 12 years. Survival data in Canada is very similar with median OS of > 10 years.
Outcomes of patients with R/R myeloma continues to be an additional important area of unmet need. Clinical data have reported poor outcomes for patients who have become refractory to PIs, IMiDs and MoAb’s, with progression- free survival (PFS) of 3.4 months and OS of 9.3 months. This has been confirmed, as well, by real-world data from Canadian patients, with reported PFS of 4.4 months and OS of 10.5 months in triple-class refractory patients.
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