A phase 2 evaluation of daratumumab-based induction therapy in patients with multiple myeloma with severe renal insufficiency.

• DOI: 10.1200/jco.2023.41.16_suppl.8057
• Publication Date: 2023-06-04T16:11:56Z
• Authors: R. Donald Harvey; Joseph Franz; Nisha S Joseph; Jonathan L. Kaufman; Elise Hitron; Hannah Collins; Catherine Braga; Kathryn T. Maples; Craig C. Hofmeister; Madhav V. Dhodapkar; Sagar Lonial; Ajay K. Nooka
• Keywords: Daratumumab; Tolerability

8057 Background: Myeloma patients (pts) with renal insufficiency (RI) have inferior disease outcomes; up to 50% present acute kidney injury (AKI). AKI results from light chain-induced cast nephropathy; physicochemical properties (self-association, aggregate formation) may determine severity. Daratumumab has extensive data in myeloma, reduces circulating chains, preserves function AL amyloidosis, and non-renal clearance. We hypothesized early therapy daratumumab VRD normalize myeloma-induced a population rarely included trials. Methods: used Simon’s two-stage design newly diagnosed pts severe (CrCl <30 mL/min) of 4 x 21-D cycles 16mg/kg IV QW 3 (C1-3, C4D1 only), bortezomib 1.3 mg/m 2 SQ D1, 4, 8, 11, dexamethasone 40mg (reduced 20mg at C2 for ≥75 yrs.) D1-4 (C1 only, D1 only C2-4), 15, add-on lenalidomide (25mg if CrCl ≥30 mL/min). Standard antiviral, antithrombotic, premedications were used. Eligibility criteria broad mL/min, PS 0-2, ANC>1000/mm , Hgb>7 g/dL, plt>75,000/mm ) liberal dose reductions generalizability. Primary objective: proportion recovery ≥50 after cycles; secondary objectives: best response (IMWG), end treatment, density/tolerability, adverse events (AE), change by estimates [Cockcroft-Gault (C-G), MDRD, 24-hour urine, CKD-EPI], PK. If ≥7 responses seen the first 11 pts, 14 more would be accrued. These are planned analysis initial cohort. Results: Thirteen enrolled: 8 male, 7 white/6 black, median age 69 yr (46-82), treated/evaluable primary endpoint. Median baseline 13.8 mL/min (4.9-20.2), serum creatinine (SCr) 4.92 mg/dL (3.53-9.93). One withdrew consent, 1 was inevaluable (rapid progression death). Seven achieved (median C3D1 61 22-151) cycles, all had SCr improvement C3D1. Lenalidomide 25 mg on C2D1 9/11 pts. (range) density (delivered/planned): 100% (40-100), (25-100), 80% (67-100), (0-100). The overall rate 100%, ≥VGPR 82%. Best CR (3), VGPR (6), PR (2). Treatment-emergent grade ¾ hematologic AEs: anemia (90.9%), lymphopenia (81.8%), thrombocytopenia (36.4%), neutropenia (9.1%). Conclusions: Early, aggressive daratumumab-based induction regimen myeloma improves function, majority achieving responded. AEs consistent prior experience 4-drug regimen. Per protocol, additional will accrued second stage. Clinical trial information: NCT04352205 .