Abstract
Background and Aim: Patients diagnosed with multiple myeloma and refractory to both proteasome inhibitors(PI) and immunomodulatory drugs (IMID) are in need of novel drugs. We aimed to analyze the efficacy and safety of daratumumab, a novel CD38-targeted monoclonal antibody, in Turkey.
Patients and Methods: In this open-label, multicenter, early access program approach performed in 24 sites in Turkey, 39 patients (age ≥18 years) with multiple myeloma who were previously treated with at least 3 lines of therapy (including PI and IMID), or were refractory to both PI and IMIDs, were evaluated to receive intravenous daratumumab 16 mg/kg for 8 weeks (cycles 1 and 2), then every 2 weeks for 16 weeks (cycles 3-6), and then every 4 weeks thereafter (cycle 7 and higher). The primary endpoint was overall response rate (ORR)(partial response [PR] + very good PR + complete response [CR] + stringent CR). All patients who received at least one dose of daratumumab were included in the statistical analysis.
Results: The first patient was enrolled in June 2016, enrollment was completed in January 2017 and follow-up is ongoing. Findings are reported for the 39 patients who met eligibility criteria (Table 1). Patients had received a median of 5 previous lines of therapy (range 3-8) and autologous stem cell transplantation (79,5 %). Median duration of Daratumumab treatment was 5.5 months (range: 0.2-13.2). 11 patients are still on treatment. Daratumumab was well tolerated; thrombocytopenia (11 [28.2%]), fatigue (10 [25.6%] patients) and anemia (10 [25.6%]) of any grade were the most common adverse events. No drug-related adverse events led to treatment discontinuation. ORR was noted in 14 patients (35.9%, 95% CI: 20.8-50.9) (CR:2 (5.1%, 95% CI: 0.6-17.3), VGPR: 1(2,6%) and PR:11 (28.2%, 95% CI: 15.0-44.9). The median time to first response was 1·0 month (range 0.5-7.5) (Figure 1). Median duration of response was 4.9 months (95% CI: 4.37-7.77) and progression-free survival was 5.5 months (95% CI: 2.2-8.8). 28 patients progressed on treatment. Thirteen of these patients died due to infections and progression. The 12-month overall survival is 56.9%.
Conclusion: This multicenter Daratumumab monotherapy study showed encouraging efficacy in heavily pretreated and refractory myeloma patients with a favorable safety profile. However, there is a need to improve the response by combining with i.e. IMID and/or PIs.
Acknowledgment: We are thankful to centers (Anadolu, Pamukkale, Cukurova, Adana Baskent, Dokuz Eylul, Erciyes, Karadeniz, Ankara, Acibadem Atasehir, Florence Nightingale, Istanbul University, Numune, Ataturk Hospitals) who enrolled less than two patients and could not be included among the authors.
No relevant conflicts of interest to declare.
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