Diffuse Large B Cell Lymphoma

ROBUST: A Phase III Study of Lenalidomide plus R-CHOP Versus Placebo plus R-CHOP in Previously Untreated Patients with ABC-Type Diffuse Large B-Cell Lymphoma

ROBUST: A Phase III Study of Lenalidomide plus R-CHOP Versus Placebo plus R-CHOP in Previously Untreated Patients with ABC-Type Diffuse Large B-Cell Lymphoma


In the April 20, 2021 edition of Journal of Clinical Oncology, investigators report on the results of the ROBUST trial.

Background:

Patients with activated B-cell like diffuse large B-cell lymphoma, have historically shown inferior survival outcomes with standard R-CHOP therapy.  The investigators developed a phase 3 clinical trial, adding the immunomodulatory agent, lenalidomide, the standard R-CHOP, R2-CHOP.  This was based off a very successful phase 2 clinical trial, using R2-CHOP, previously untreated activated B-cell type diffuse large B-cell lymphoma.

Methods:

Both histology and cell of origin type were analyzed prospectively prior to random assignment by central pathology center.  Patients with activated B-cell subtype were treated with lenalidomide 50 mg daily orally, 14 out of 21 days plus standard R-CHOP21.  Treatment was administered for 6 cycles.  Progression free survival as the primary endpoint.

Results:

570 patients are randomized, 285 neutrophils.  Patients were stratified by international prognostic index score, tumor bulkiness and patient age to either R-CHOP plus placebo or R2-CHOP.  The majority of patients completed all 6 cycles, 74% of the treatment arm and 84% in the standard placebo arm.  The most common grade 3 and 4 adverse events in the treatment arm, included neutropenia at 60%, anemia 22% and thrombocytopenia at 17%.  This was in comparison to the standard arm of 40%, 40%, 11% respectively.  The primary endpoint of progression free survival was not met.  The hazard ratio 0.85, P = 0.29 with median progression free survival not reached in either arm.  Progression free survival chance favoring R2-CHOP were seen in patients with high-risk disease.

The authors concluded “ROBUST is the first DLBCL phase III study to integrate biomarker-driven identification of eligible ABC patients. Although the ROBUST trial did not meet the primary end point of PFS in all patients, the safety profile of R2-CHOP was consistent with individual treatments with no new safety signals.”

Https://ascopubs.org/doi/full/10.1200/JCO.20.01366

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