## 1 Introduction  
Multiple myeloma (MM) is a hematologic malignancy characterized by monoclonal proliferation of plasma cells that leads to bone disease, including lytic lesions and osteoporosis [1,2]. In Japan, MM accounts for about 10% of hematopoietic malignancies and causes approximately 4000 deaths each year [2]. Although treatment options have increased [3, 4, 5, 6], and novel drugs have been shown to improve overall survival (OS) in Japanese myeloma patients [7], optimal management of patients with MM remains challenging, particularly regarding treatment selection and sequencing. A real-world US-based study showed that transplant-ineligible newly diagnosed MM (NDMM) patients had increasing attrition rates in later treatment lines, highlighting the importance of selecting the optimal regimen as early as possible [8, 9, 10, 11]. Daratumumab is a human IgG1x mAb targeting CD38. Multiple regimens containing daratumumab are standard of care in Japan [2]. Daratumumab + lenalidomide + dexamethasone (DRd) and daratumumab + bortezomib + dexamethasone (DVd) were approved in Japan in September 2017 for patients with relapsed or refractory MM (RRMM) [12]. In August 2019, daratumumab + bortezomib + melphalan + prednisolone (DVMP) was approved in Japan for transplant-ineligible NDMM, and in December 2019, DRd was also approved for this indication [12]. Subsequently, approval was granted in Japan for daratumumab + carifizomib + dexamethasone (DKd; November 2020) [12], and daratumumab + pomalidomide + dexamethasone (DPd; December 2021) for RRMM. A subcutaneous formulation of daratumumab is also available in Japan (approved in March 2021) [13]. DRd is the only regimen available in Japan for the treatment of both NDMM and RRMM, and it is increasingly used in 1L in Japanese clinical practice [14]. Its efficacy in MM as first-line (1L) and second-line (2L) or later treatment was demonstrated in the MAIA [15] and POLLUX studies [16]. In the interim analysis of the phase 3 MAIA study in patients with transplant-ineligible NDMM, DRd was associated with significantly improved OS (hazard ratio [HR] 0.68; \(p\) = 0.0013) and progression-free survival (PFS; HR 0.53; \(p\) < 0.0001) compared with lenalidomide + dexamethasone (Rd) alone after a median follow-up of 56.2 months, and significantly prolonged PFS on next line of treatment (PFS2) compared with Rd alone (HR 0.61; \(p\) < 0.0001) [15]. The recently released long-term follow-up analysis of the MAIA study confirmed these findings, with a 33% reduction in the risk of death with DRd versus Rd (HR 0.67; \(p\) < 0.0001) at a median follow-up of 89.3 months [17]. In the phase 3 POLLUX study, patients with RRMM who had received \(\geq\)1 prior lines of therapy were treated with DRd or Rd [16, 18, 19, 20]. At a median follow-up of 44.3 months, DRd significantly prolonged PFS compared with Rd (HR 0.44; \(p\) < 0.0001) [20]. Furthermore, a significant improvement in OS was observed with DRd versus Rd at 79.7 months (HR 0.73; \(p\) = 0.0044) [19]. The survival benefits in both these trials were maintained in subgroups defined by older age (\(\geq\)75 years in the MAIA study [15] and \(\geq\)65 years in the POLLUX study [19]). In a simulation study of data from the MAIA study and real-world US data from the Flatiron Health database, patients with transplant-ineligible NDMM had a prolonged median OS with 1L DRd compared with 2L daratumumab administration after bortezomib + Rd (VRd) or Rd [21]. This suggests that 1L DRd may provide greater benefits over daratumumab-based regimens in later lines of treatment in this population. A database study in Japan found a shift in MM treatment patterns in recent years, with shorter 1L treatment durations and a move toward regimens that incorporate newer drugs in subsequent lines [3].