Эффективность терапии даратумумабом в реальной клинической практике у пациентов с рецидивирующей/рефрактерной множественной миеломой

Abstract

Introduction. Despite the availability and high effectiveness of modern anticancer drugs used to treat patients with multiple myeloma (MM), most patients inevitably develop disease relapses and refractoriness to the ongoing therapy. The prognosis in patients with relapsed MM and refractoriness to the main classes of anticancer drugs (proteasome inhibitors and immunomodulators) remains poor, and the median overall survival (OS) is only 8 months. Daratumumab is the first fully human IgG1-κ monoclonal antibody that binds with high affinity to the CD38 protein on the surface of myeloma cells, has a direct effect on the tumor, and also has an immunomodulatory mechanism of action. In clinical trials, daratumumab has been shown high effective and safety when used as monotherapy in patients with relapsed and double refractory MM. Aim. To evaluate the effectiveness and safety of daratumumab monotherapy in patients with relapsed/refractory multiple myeloma (RRMM) in real-life clinical practice. Materials and methods. We analyzed 32 patients with RRMM (14 men and 18 women) aged 41–76 years (median 65 years) from two hematological centers in the city of Novosibirsk. In 65.6% of patients, stage IIIA according to Durie-Salmon, stage I–II according to the ISS (in 65.6 and 28.1% of patients, respectively), ECOG performance status 0–1 (in 37.5 and 43.7% of patients, respectively) were diagnosed. Bone-related soft tissue plasmacytomas were recorded in 56.3% of patients, high lactate dehydrogenase activity was noted in 12 (37.5%) patients. The median number of prior lines of therapy was 2 (range 2–4). All patients had previously received proteasome inhibitors (bortezomib) and immunomodulatory agents (lenalidomide). Autologous hematopoietic stem cells transplantation was performed in 34.4% of patients. Double refractory MM was registered in 24 (75%) of 32 patients. The median time from diagnosis of MM to initiation of daratumumab therapy was 73.1 months (range 18–144 months). Daratumumab was administered as monotherapy at a dose of 16 mg/kg intravenously weekly (cycles 1–2), every other week (cycles 3–6), and then monthly. Results. The median duration of therapy with daratumumab was 12.2 months (range 4–22 months). The overall response rate (complete response + very good partial response (vgPR) + partial response (PR)) was 67.7%; vgPR – in 9 (29%) patients, PR – in 12 (38.7%), stable disease (SD) was registered in 19.4% of patients, respectively. The median time to response was 3.5 months (range 2.5–6). The median duration of response was 7.9 months (95% confidence interval (CI) 4.7–11.5). The median progression-free survival (PFS) was 19.1 months (95% CI 15.3–23.6), and the 12- and 18-month PFS were 91% and 50%, respectively. The median OS was not reached, and the 12- and 18-month OS values were 100% and 96.3%, respectively. The depth of the response had a statistically significant effect on the PFS (18-month PFS was 100% in the vgPR and PR subgroups and 81% in the SD subgroup, respectively (χ2 = 19.207, p < 0.001)). Therapy with daratumumab was accompanied with a favorable toxicity profile. In 37.5% of patients, grade 1 and 2 infusion reactions were noted, in 6.2% grade ≥ 3, in one patient, therapy was discontinued due to an infusion reaction of the 3rd degree. Fatigue, upper and lower respiratory tract infections (15.6% and 12.5%, respectively), anemia (15.6%), thrombocytopenia (6.2%), and neutropenia (6.2%) were recorded in 15.6% of patients. Conclusion. Therapy with daratumumab is an effective and safe treatment for RRMM.