A phase I/II study of carfilzomib, iberdomide (CC-220), and dexamethasone (KID) in patients with newly diagnosed transplant-eligible multiple myeloma.
Authors: Biran Noa , Vesole David H. , Parmar Harsh V. , Phull Pooja , Doucette Kimberley , Feinman Rena , Zenreich Joshua , Anand Palka , Ivanovski Kristin , Pace Monique , Breeze Genevieve , Amer Rania , Biamonte Lisa , Aleman Adolfo , Unawane Rashmi , Pendergrass Elizabeth , Della Pia Alexandra , Kumka Susan , Siegel David Samuel DiCapua 
Published: June 2023

e20043

Background: Iberdomide is a next generation cereblon-E3 ligase modulating agent (CELMoD) that has increased antitumor activity relative to earlier thalidomide analogs (IMiDs). This is due to direct effects on tumor cells and increased immune surveillance. Herein, we report the dose escalation, safety and efficacy data from this ongoing study of carfilzomib (CFZ), iberdomide, and dexamethasone (DEX) (KID) in patients with newly diagnosed transplant-eligible multiple myeloma (MM). Methods: This is a phase I/II, multicenter study of KID in patients with newly diagnosed transplant-eligible MM. Patients were enrolled in a standard 3+3 design to determine the maximum tolerated dose (MTD) of iberdomide (starting dose 1 mg; D1-21) in combination with CFZ (IV; 20 mg/m2 on C1D1; 56 mg/m2 C1D8, D15; 56 mg/m2 C2-4, D1, 8, 15) and DEX (D1, 8, 15) in 28-day cycles. Enrollment is ongoing with a 3 level dose escalation phase (max dose of iberdomide 1.6 mg) followed by a planned dose expansion phase. The phase I primary objective is to determine the safety of KID. The phase II primary objective is to evaluate the rate of complete remission (CR) + stringent CR (sCR) for patients receiving 2-4 cycles of KID followed by ASCT and 6 cycles of iberdomide consolidation. Results: At data cutoff (Feb 6, 2023), there were 8 patients who had signed consent for the trial, of whom 1 is actively receiving treatment, 5 are in follow up, and 2 were screen failures. Of the 6 patients on trial, the median age was 61 years (range 46-74), 33% male, 67% white, and 17% with ISS stage II MM. Two patients had high-risk cytogenetics, including one patient with t(14;16) and one patient with 1q21 duplication and TP53 mutation. Three patients enrolled at the starting dose level of iberdomide 1 mg orally on D1-21. Grade 1-2 TEAEs occurred in all 3 patients, and one patient experienced a grade 3 TEAE (neutropenia). Three patients were enrolled at the next dose level of iberdomide 1.3 mg orally on D1-21. Grade 1-2 TEAEs occurred in 2 patients (rash and pruritus), but no grade ≥3 TEAEs occurred in any of these 3 patients. To date, no patients have experienced a DLT and the MTD has not been reached. The median number of cycles of KID was 3 (range 3-4) for the 5 patients who completed treatment. Four patients proceeded to ASCT and 2 patients are pending evaluation. The median amount of stem cells mobilized was 9.42 x 106 cells/kg (range 6.7-11.45). Response data at 3 months post-ASCT is available for 1 patient, who is in CR + sCR and MRD-negative. Conclusions: Induction therapy with KID appears safe with the only grade 3 TEAE reported being neutropenia. In patients who completed treatment, induction cycles with KID did not interfere with stem cell mobilization. Correlative and additional clinical data are being collected and will be presented. Clinical trial information: NCT05199311 .