Real-World Data on the Efficacy of Daratumumab in Patients with Relapsed/Refractory Multiple Myeloma and Amplification 1q

<b>Background:</b> Treatment of multiple myeloma has advanced tremendously with the approval of anti-CD38 antibodies. Their efficacy is impressive but still controversial in the 1q amplification subgroup (amp1q). This retrospective study aims to provide real-world data. <b>Methods:</b> This trial is analyzing 74 patients with relapsed/refractory multiple myeloma treated with CD38Abs at the Medical University of Innsbruck (2016-2023). High-risk (HR) cytogenetics according to R-ISS (t(4;14), t(14;16), t(14;20), del(17p)), the presence of amp(1q21), the frequency of two HR markers (double hit), and the high-risk criteria agreed at IMS 2024 (HR-IMS24) were considered. <b>Results:</b> The median age of the 74 patients (62.1% male) was 62 years, with a median follow-up of six years. Most patients received third-line therapy (37.8%). R-ISS HR was documented in 39.2% of patients, double hit in 13.5% of patients, and HR-IMS24 in 32.4% of patients, while amp1q was detected in 35.1% of patients. The median OS was 66 months (35-89), and the median PFS was 17 months (6.5-26.9). While neither R-ISS HR nor isolated amp1q had an impact on progression-free survival (e.g., amp1q 7.03: 1.95-22.44; <i>p</i> = 0.347), the occurrence of a double-hit pattern significantly impaired PFS and OS (6.2: 1.4-16.4 months; <i>p</i> = 0.044; OS, 42.8: 25.9-74.6 months; <i>p</i> = 0.035). Patients fulfilling the HR-IMS24 criteria (32.4%, 24 patients) also exhibited an impaired PFS and OS (7: 2.7-18.1 months, <i>p</i> = 0.023; 40.12: 21.1-74.5 months, <i>p</i> = 0.01). <b>Conclusions:</b> This retrospective study highlights the durable effect of daratumumab on cytogenetic abnormalities, particularly amp1q. However, patients who meet the criteria for double-hit myeloma or the high-risk IMS2024 criteria remain a difficult-to-treat patient population who require early access to new treatment approaches.