The combination of iberdomide (CC-220), an oral cereblon E3 ligase modulator agent that is known to reduce lymphoma cell survival, and an anti-CD20 monoclonal antibody yielded safe and effective results for patients with relapsed/refractory (R/R) lymphoma, according to findings from a phase 1/2 open-label study. 

At the 2022 ASH Annual Meeting and Exposition in New Orleans, Louisiana, Catherine Thieblemont, MD, PhD, Hôpital Saint-Louis, Paris, France, presented data from the phase 1/2 study. 

46 patients with various types of R/R lymphomas who had undergone ≥2 prior lines of treatment were enrolled in this study. The median age was 69 years. Patients were split into 3 cohorts: cohort A consisted of patients with all lymphomas, who were administered escalating doses of iberdomide alone; cohort B consisted of patients with all B-cell lymphomas, who were administered iberdomide, along with rituximab (≤6 cycles); cohort 3 consisted of patients with marginal zone lymphoma (MZL) or grade 1 to 3a follicular lymphoma (FL), who were administered iberdomide, along with obinutuzumab (≤6 cycles). 

As of March 31, 2022, results of this study showed that iberdomide was well- tolerated by patients, with the most common treatment-emergent adverse events (TEAEs) affecting ≥ 10%, being neutropenia, anemia, thrombocytopenia, and constipation. The majority of these adverse events were hematologic in nature and were manageable with the use of granulocyte colony-stimulating factor (G-CSF). 

Iberdomide had an overall response rate (OR) of 55% and a complete remission rate (CR) of 32% among evaluable patients (n=38). The response rates were similar, regardless of the type of lymphoma each patient had or their prior treatment history. 

The pharmacokinetics (PK) indicated that iberdomide was rapidly absorbed and that exposure increased in a dose-related manner. Higher doses of iberdomide were associated with greater reductions in ikaros and aiolos. 

As endpoints were met, Thieblemont et al concluded, “[Iberdomide] alone and in combination with anti-CD20 mAbs showed promising activity in pts with RR lymphoma. CELMoD agent-associated neutropenia was a predictable on-target toxicity manageable with G-CSF use and did not appear to increase risk of febrile neutropenia or infections,” adding, “These data highlight the potential of CELMoD agent-based tx in pts with R/R lymphoma to address unmet needs such as treating disease progression after CAR-T cell [treatment].” 

Source: 

Thieblemont C, Munoz J, Tucci A, et al. Iberdomide (CC-220) Monotherapy or in Combination with an Anti-CD20 Monoclonal Antibody As Effective Therapy in Patients with Relapsed/Refractory Lymphoma: Early Results from a Phase 1/2 Study. Presented at ASH Annual Meeting and Exposition; December 10-13, 2022; New Orleans, LA. Abstract 233.