Ramasamy, Karthik

AbstractThe development of novel agents has transformed the treatment paradigm for multiple myeloma, with minimal residual disease (MRD) negativity now achievable across the entire disease spectrum. Bone marrow–based technologies to assess MRD, including approaches using next-generation flow and next-generation sequencing, have provided real-time clinical tools for the sensitive detection and monitoring of MRD in patients with multiple myeloma. Complementary liquid biopsy–based assays are now quickly progressing with some, such as mass spectrometry methods, being very close to clinical use, while others utilizing nucleic acid–based technologies are still developing and will prove important to further our understanding of the biology of MRD. On the regulatory front, multiple retrospective individual patient and clinical trial level meta-analyses have already shown and will continue to assess the potential of MRD as a surrogate for patient outcome. Given all this progress, it is not surprising that a number of clinicians are now considering using MRD to inform real-world clinical care of patients across the spectrum from smoldering myeloma to relapsed refractory multiple myeloma, with each disease setting presenting key challenges and questions that will need to be addressed through clinical trials. The pace of advances in targeted and immune therapies in multiple myeloma is unprecedented, and novel MRD-driven biomarker strategies are essential to accelerate innovative clinical trials leading to regulatory approval of novel treatments and continued improvement in patient outcomes.

PURPOSE To evaluate the effects of daratumumab, lenalidomide, and dexamethasone (D-Rd) versus lenalidomide and dexamethasone (Rd) on patient-reported outcomes (PROs) in the phase III MAIA study. PATIENTS AND METHODS PROs were assessed on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item and the EuroQol 5-dimensional descriptive system at baseline and every 3 months during treatment. By mixed-effects model, changes from baseline are presented as least squares means with 95% CIs. RESULTS A total of 737 transplant-ineligible (TIE) patients with newly diagnosed multiple myeloma were randomly assigned to D-Rd (n = 368) or Rd (n = 369). Compliance with PRO assessments was high at baseline (> 90%) through month 12 (> 78%) for both groups. European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item global health status scores improved from baseline in both groups and were consistently greater with D-Rd at all time points. A global health status benefit was achieved with D-Rd, regardless of age (< 75 and ≥ 75 years), baseline Eastern Cooperative Oncology Group (ECOG) performance status score, or depth of response. D-Rd treatment resulted in significantly greater reduction in pain scores as early as cycle 3 ( P = .0007 v Rd); the magnitude of change was sustained through cycle 12. Reductions in pain with D-Rd were clinically meaningful in patients regardless of age, ECOG status, or depth of response. Similarly, PRO improvements were observed with D-Rd and Rd on the EuroQol 5-dimensional descriptive system visual analog scale score. CONCLUSION D-Rd compared with Rd was associated with faster and sustained clinically meaningful improvements in PROs, including pain, in transplant-ineligible patients with newly diagnosed multiple myeloma regardless of age, baseline ECOG status, or depth of treatment response.