POS-799 EFFECT OF DARATUMUMAB/BORTEZOMIB/CYCLOPHOSPHAMIDE/DEXAMETHASONE ON RENAL FUNCTION AND HRQOL IN PATIENTS WITH NEWLY-DIAGNOSED AL AMYLOIDOSIS WITH RENAL INVOLVEMENT: RESULTS FROM THE PHASE 3 ANDROMEDA STUDY

Abstract

Systemic light chain (AL) amyloidosis is a rare disease characterized by amyloid fibril deposits, most commonly in the heart and kidneys; the extent of organ involvement impacts clinical outcomes. There are currently no approved treatments for AL amyloidosis. Although treatments for multiple myeloma (MM), including bortezomib, cyclophosphamide, and dexamethasone (VCd), have been shown to improve outcomes, more effective therapies are needed. Daratumumab (DARA) is an anti-CD38 monoclonal antibody approved as monotherapy and in combination with other agents for the treatment of MM. In the phase 3 open-label ANDROMEDA trial (NCT03201965), patients with newly diagnosed AL amyloidosis treated with DARA subcutaneous (DARA SC) + VCd (DARA-VCd) had improved objective hematologic and organ response rates over 6 cycles of treatment. Here, we present change in renal function and patient-reported outcomes (PROs) in patients with baseline (BL) renal involvement from ANDROMEDA. Patients (N=388) with newly diagnosed AL amyloidosis with measurable hematologic disease, ≥1 involved organ, estimated glomerular filtration rate (eGFR) ≥20 mL/min, and absence of symptomatic MM were randomized 1:1 to DARA-VCd or VCd for 6 28-day cycles; thereafter, patients in the DARA-VCd group received DARA SC alone every 4 weeks up to 24 cycles. The percentage of patients with renal improvement (≥30% decrease in proteinuria or drop in proteinuria below 0.5g/24 hour in the absence of ≥25% decrease in eGFR) was also determined. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item (EORTC QLQ-C30) improvement in global health status (GHS) and fatigue scale scores were secondary study endpoints. Here we report PRO results for Cycles 1–6 (assessed on Day 1 of each cycle). Analyses were performed in the subset of patients with renal involvement, defined as 24-hour urine protein >0.5g/day, predominantly albumin. Change from BL at various time points was analyzed using a mixed-effects model with repeated measures with patients as a random effect, and BL value, treatment group, time (weeks), and treatment-by-time interaction as fixed effects. For selected single items of the EORTC QLQ-C30, the distribution of responses and the number and percentage of patients with ≥1-point improvement from BL were summarized at each time point. Of the total population in ANDROMEDA, 115 and 114 patients in the DARA-VCd and VCd groups had renal involvement, respectively; 117 and 113 patients were evaluable for renal response. At 6 months, 53.8% of DARA-VCd and 27.4% of VCd patients had a renal response (P<0.0001). GHS (Figure) and fatigue scores remained stable with DARA-VCd but worsened with VCd by Cycle 3; the greatest between-group differences were observed at Cycle 5. At BL, 56–85% of patients reported shortness of breath, feeling weak or tired by ‘a little’ or more (Table). More DARA-VCd than VCd patients experienced ≥1-point improvements in these symptoms (Table). DARA-VCd increased renal response, with results suggestive of improvement in fatigue-related parameters, such as shortness of breath, feeling tired, or weak, in AL amyloidosis patients with renal involvement.