Predictive Markers of High-Grade or Serious Treatment-Emergent Infections with Daratumumab-Based Regimens in Newly Diagnosed Multiple Myeloma (NDMM)

Introduction: Daratumumab (DARA) is a CD38-targeting monoclonal antibody approved for the treatment of MM. The addition of DARA to standard-of-care (SOC) regimens in the phase 3 ALCYONE (D-VMP vs VMP) and MAIA (D-Rd vs Rd) studies demonstrated deep and durable responses and improved progression-free survival in transplant-ineligible NDMM patients (pts). DARA-based regimens have shown increased infection rates vs SOC in both ALCYONE (grade 3/4 infections, 22% vs 15%) and MAIA (36% vs 27%). Most common (>10 pts) grade 3/4 infection(s) was pneumonia (D-VMP/VMP; 13%/4%) in ALCYONE and were pneumonia (D-Rd/Rd; 15%/9%), influenza (3%/2%), bronchitis (3%/1%), and sepsis, urinary tract and lower respiratory tract infections (3% each) in MAIA. Most common (>10 pts) serious adverse infection(s) was pneumonia (D-VMP/VMP; 12%/3%) in ALCYONE and pneumonia (D-Rd/Rd; 14%/9%), influenza (4%/2%), bronchitis (4%/2%), and upper respiratory tract infection (3%/3%) in MAIA. Using pooled data from DARA-treated pts in ALCYONE and MAIA, we report results of an analysis to identify predictive markers of grade ≥3 or serious infections that occurred during the first 6 mo of treatment. Methods: ALCYONE pts received ≥nine 6-week cycles of VMP (V: 1.3 mg/m2 SC on Days 1, 4, 8, 11, 22, 25, 29, and 32 of Cycle 1 and Days 1, 8, 22, and 29 of Cycles 2-9; M: 9 mg/m2 orally, and P: 60 mg/m2 orally on Days 1-4 of Cycles 1-9)±DARA (16 mg/kg IV), QW during Cycle 1, Q3W Cycles 2-9, and Q4W thereafter as maintenance therapy until disease progression or unacceptable toxicity. MAIA pts received 28-day cycles of Rd (R: 25 mg PO once daily on Days 1-21; d: 40 mg PO on Days 1, 8, 15 and 22)±DARA (16 mg/kg IV) QW Cycles 1-2, Q2W Cycles 3-6, and Q4W weeks thereafter. This analysis pooled data for DARA-treated pts in ALCYONE (median follow-up, 40.1 mo) and MAIA (median follow-up, 36.4 mo). Pooled data were randomly split into training and validation data. A predictive model was developed for time to first occurrence of treatment-emergent grade ≥3 or serious infections during the first 6 mo of study treatment. To identify the set of predictors for the Cox proportional hazard multivariate model, each candidate predictor was first assessed in a univariate model. Parameters with a P value