Background: We report updated data from a Phase Ib study of Isa, a CD38 monoclonal antibody, plus VCd or VRd in transplant ineligible patients (pts) with NDMM (NCT02513186). Methods: Isa-VCd: Isa (10 or 20 mg/kg; weekly [QW] cycle 1 [C1], then Q2W), V (1.3 mg/m²; twice weekly C1, then QW), C (300 mg/m²; QW C1, then Days [D] 1, 8, 15 to C12), d (20 mg; twice weekly C1, then D1, 2, 8, 9, 15, 16, 22, 23 to C12). Isa-VRd: Isa (10 mg/kg), V and d as described above; R (25 mg/day; D1–14 and D22–35). Efficacy and safety were evaluated. Conventional (M-protein levels) and minimal residual disease (MRD) IMWG response assessments were compared. MRD negativity was assessed at 10⁻⁵ by next-generation sequencing and flow. Mass Spectrometry (MS) negativity (no detectable serum M-protein) was assessed for 13 pts by Immuno-Capture and Liquid Chromatography coupled to High Resolution MS. Results: As of Nov 18, 2019, 17 pts were treated with Isa-VCd (10 mg/kg, n = 13; 20 mg/kg, n = 4), 27 with Isa-VRd; 53% and 63% remained on treatment, respectively. Infusion reactions were seen in 53% of Isa-VCd and 63% of Isa-VRd pts; Grade ≥3 infections in 23% and 37%; serious adverse events in 47% and 52%. See table for efficacy. 3 MRD positive pts were MS positive with persistent detectable M-protein ( > 10 µg/mL). 8/10 MRD negative pts were MS positive (4 at 5-10 µg/mL; 4 at > 10 µg/mL) and 2/10 were MS negative ( < 5 µg/mL). Stable residual M-protein was observed by MS up to 23 months post-MRD negativity. All pts tested by MS are still progression-free. Conclusions: Isa-VCd/VRd shows encouraging efficacy and tolerability in NDMM. MS seems to be more sensitive than MRD; low levels of M-protein were detectable even in MRD negative pts. Clinical trial information: NCT02513186.

CI, confidence interval; CR, complete response; PFS, progression free survival; ORR, overall response rate; PR, partial response; VGPR, very good partial response.