Real-World Clinical Outcomes of Daratumumab-Based Regimens in Chinese Patients with Multiple Myeloma By Cytogenetic Risk: A Subgroup Analysis of the MMY4032 Study

Introduction: Daratumumab (DARA), a human IgGκ monoclonal antibody targeting CD38, has demonstrated favorable clinical efficacy in several multiple myeloma (MM) clinical trials. Rigorous study designs and restrictive eligibility criteria, however, necessitate the need for real-world studies to provide complementary data better reflecting the effectiveness and safety of MM treatments in routine clinical practice. In the first interim analysis of the real-world MMY4032 study (ChiCTR2200055491), DARA appeared effective and safe in Chinese patients with MM. However, patients with MM and high-risk disease characteristics, such as high-risk cytogenetic abnormalities (HRCAs), often face poor overall prognosis and represent a high unmet medical need. Here, we present a subgroup analysis of the MMY4032 study exploring the real-world effectiveness of DARA-based regimens in Chinese patients with MM by the baseline presence of HRCAs. Methods: This ongoing, noninterventional, observational study enrolled Chinese patients with MM who either started DARA treatment after August 1, 2019, and were expected to continue ongoing DARA at the time of study initiation (November 3, 2021) or started DARA treatment after study initiation; patients must have received ≤3 lines of therapy prior to initiating DARA. The decision to treat with DARA must have been made independently of, and prior to, the patient's inclusion in the study, with DARA administered in accordance with local clinical practice. Retrospective data were collected using medical charts for patients who initiated DARA after August 1, 2019, but prior to study initiation; prospective data was collected thereafter. HRCAs were assessed by fluorescence in situ hybridization (FISH). High cytogenetic risk was defined as the presence of ≥1 of the following HRCAs: del(17p), t(4;14), t(14;16), t(14;20), gain(1q21) (3 copies of chromosome 1q21), and amp(1q21) (≥4 copies of chromosome 1q21). Cytogenetic risk subgroups evaluated included standard risk (0 HRCAs), high risk (≥1 HRCA), and 1 HRCA. Clinical outcomes of interest included overall response rate (ORR; partial response or better) and 12-month progression-free survival (PFS) and overall survival (OS) rates. Results: A total of 212 patients were enrolled and had received ≥1 dose of DARA, 76 of whom had FISH data. Among these 76 patients, the median (range) age at baseline was 60 (29-84) years and 42.1% were female. DARA was predominantly initiated in the second line of therapy (first line, 21.1%; second line, 61.8%; third line, 10.5%; fourth line, 6.6%). Approximately half of the patients (47.4% [n=36]) had standard cytogenetic risk and half (52.6% [n=40]) had high cytogenetic risk; 36.8% (n=28) of patients had 1 HRCA. Among 189 patients in the response-evaluable population, 67 had FISH data and response results. The ORR was 78.1% (n=25/32) in patients with standard cytogenetic risk, 82.9% (n=29/35) in those with high cytogenetic risk, and 87.0% (n=20/23) in those with 1 HRCA. At a median follow-up of 16.8 months, estimated 12-month PFS rates were 92.7% in patients with standard cytogenetic risk, 69.3% in those with high cytogenetic risk, and 76.9% in those with 1 HRCA. Estimated 12-month OS rates were 97.1% in patients with standard cytogenetic risk, 82.4% in those with high cytogenetic risk, and 82.1% in those with 1 HRCA. Observed differences in PFS and OS rates for patients with standard versus high cytogenetic risk were not statistically significant. Conclusions: Data from this ongoing, noninterventional, observational real-world study demonstrate that Chinese patients with MM can achieve clinical benefit when treated with DARA-based regimens, irrespective of cytogenetic risk profile. These results continue to support the use of DARA-based treatment as a standard of care in Chinese patients with newly diagnosed or relapsed/refractory MM.