Conference Coverage

A Phase 2 Quadruplet Regimen Shows High MRD-Negativity Rates in Early Relapsed/Refractory Multiple Myeloma: ReKInDLE Study

Edited by:
Kate Young

Key Highlights

  • Quadruplet therapy achieved MRD-negativity at 10⁻⁵ in 66.7% of evaluable patients.
  • Overall response rate reached 92.3%, with 38% achieving complete response or better.
  • Toxicities were primarily hematologic and manageable with standard supportive care.
  • Majority of patients (90%) remained on treatment, with 27% de-escalating to iberdomide monotherapy.

A single-center phase 2 investigation from the Sylvester Comprehensive Cancer Center, University of Miami, reports promising early results for ReKInDLE, a novel quadruplet regimen incorporating iberdomide for patients with early relapsed or refractory multiple myeloma (RRMM). The study, presented at the 67th American Society of Hematology Annual Meeting and Exposition, explores whether this cereblon E3 ligase modulator can overcome emerging IMiD resistance and improve depth of response in a setting where T-cell–redirecting therapies are increasingly utilized.

ReKInDLE (NCT05896228) enrolled adults with RRMM who had received one to three prior lines of therapy, including lenalidomide. Prior exposure to carfilzomib or anti-CD38 therapy was permitted unless discontinued for toxicity or progression. The protocol consisted of up to eight 28-day cycles of iberdomide, daratumumab, carfilzomib, and dexamethasone, followed by optional de-escalation to iberdomide monotherapy for responders (≥SD) for up to three years. The primary endpoint was MRD-negativity at 10⁻⁵ by next-generation sequencing following combination therapy. Secondary endpoints included safety, overall response rate (ORR), duration of response, and survival outcomes.

Study Findings

As of July 20, 2025, the study reached full enrollment (n=30). The median patient age was 63 years; 33% had high-risk cytogenetics, 17% had extramedullary disease, and 93% were lenalidomide-refractory.

Among the 12 patients evaluated for MRD after combination therapy, eight achieved MRD-negativity at 10⁻⁵ with concurrent PET-negative complete response—yielding a rate of 66.7% (95% CI, 34.9–90.1%). Of 26 response-evaluable patients, the ORR was 92.3%, with 38% achieving complete response or better and 35% achieving very good partial response.

Most participants (90%) remained on treatment at cutoff. Eight patients (27%) transitioned to iberdomide monotherapy, with some treated for up to 17 months. Hematologic adverse events were common, including grade ≥3 neutropenia (50%) and lymphocytopenia (40%). Six serious adverse events occurred, including three lung infections and isolated cases of febrile neutropenia, presyncope, and myocardial infarction. No deaths were reported.

Clinical Implications

According to the investigators, a quadruplet regimen incorporating iberdomide may offer an effective, manageable option for patients relapsing shortly after lenalidomide-based therapy—an increasingly common clinical scenario. The regimen’s ability to produce high MRD-negativity rates and allow transition to oral monotherapy may reduce reliance on continuous parenteral therapies in the early relapse setting.

Expert Commentary

“This quadruplet reinduction strategy adds another treatment alternative in the early relapse setting where parenteral T-cell redirecting therapies are gaining increased prominence,” the researchers concluded.

Reference
Landgren O, Hoffman J, Pandey A, et al. A phase 2 trial of iberdomide, carfilzomib, daratumumab and dexamethasone quadruplet therapy for relapsed/refractory multiple myeloma: The ReKInDLE study. Presented at: 67th ASH Annual Meeting and Exposition in Orlando, FL. December 6, 2025. https://submit.hematology.org/program/presentation/671664