Glofitamab Plus Gemcitabine and Oxaliplatin Demonstrates Benefit for Patients With R/R Diffuse Large B-Cell Lymphoma

Results of the STARGLO global randomized phase 3 trial

Jeremy Abramson, MD, Massachusetts General Hospital Cancer Center, Boston, Massachusetts, shares data from the global, randomized, phase 3 STARGLO trial on the benefit of treatment with CD20-CD3 bispecific antibody glofitamab plus gemcitabine and oxaliplatin (GemOx) vs rituximab-GemOx for patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) after 1 or more prior line of therapy.

These results were presented at the 2024 European Hematology Association (EHA) Congress in Madrid, Spain.

“[Glofitamab]-GemOx demonstrated statistically significant and clinically meaningful benefit in OS, PFS, and CR rate over R-GemOx in ASCT-ineligible [patients] with R/R DLBCL,” Abramson and coauthors wrote. “Glofitamab is the first CD20-CD3 bispecific antibody to demonstrate survival benefit in DLBCL in a randomized [phase 3] trial.” 

Transcript:

Hi, I'm Jeremy Abramson. I'm director of the lymphoma program at the Mass General Cancer Center in Boston, and an associate professor of medicine at Harvard Medical School. Just this month in Madrid at the annual meeting of EHA, I had the pleasure of presenting results of the STARGLO trial in the plenary session.

The STARGLO trial evaluated glofitamab plus gem gemcitabine and oxaliplatin compared to rituximab gemcitabine-oxaliplatin in patients with relapse of refractory diffuse large B-cell lymphoma after 1 or more prior lines of therapy. Glofitamab is an anti-CD20-CD3 bispecific antibody targeted against B-cell lymphomas. It was initially FDA approved based on a pivotal phase 1/2 trial as monotherapy in patients with 2 or more prior lines of therapy, where it induced deep and durable rates of complete remission.

The randomized STARGLO trial evaluates glofitamab-GemOx compared to R-GemOx in patients who are considered transplant-ineligible with 1 or more prior lines of therapy.We randomized 274 patients, 2 to 1, to receive of glofitamab-GemOx compared to R-GemOx, and the primary end point was overall survival. Key secondary end points included progression-free survival (PFS) and complete response (CR) rate. Among randomized patients, the median age was 68 years old in both arms, and the arms were generally well-balanced as far as study risk factors.

63% of patients in both arms of the study had received 1 prior line of therapy, whereas 37% had received 2 or more prior lines of therapy, and 60% of patients were refractory to their immediate prior line of lymphoma treatment. In evaluating the primary end point of overall survival (OS), found a statistically significant overall survival benefit favoring glofitamab-GemOx over glofitamab-GemOx. At the primary analysis, the hazard ratio of 0.59 reflecting a 41% reduction in risk of death, favoring glofitamab-GemOx.

With 21 months of median follow-up, the median overall survival on R-GemOx was 12 .9 months, compared to 25.5 months on glofitimab-GemOx. We also saw an improvement in progression-free survival, now with a 63% reduction in risk of progression or death favoring glofitimab-GemOx with a median of 16 months of median follow-up. The median progression-free survival was 3.6 months on R-GemOx and 13.8 months on glofitimab-GemOx.

We also saw an improvement in complete response rate, which was 58.5% on glofitimab-GemOx, compared to 25% on R-GemOx. Importantly, we found that the safety profile was consistent with the included study drugs. We did see more adverse events on the glofitimab-GemOx arm, and this generally reflected the known side effect profile of glofitimab, particularly in terms of cytokine release syndrome, cytopenias, and infections.

Specifically, we saw 44% incidence of cytokine release syndrome with glofitimab-GemOxtreatment, but importantly, this was almost entirely low-grade and occurred predominantly during the first cycle with step -up dosing, and thereafter was extremely uncommon. There was an increased risk of infections on glofitimab-GemOx, and that largely reflected an increased incidence of COVID -19.

Overall, I'd say that the STARGLO trial met its primary end point. It showed a superior overall survival, as well as progression-free survival and complete response rate with a manageable toxicity profile favoring glofitimab-GemOx over R-GemOx and supporting the use of glofitimab-GemOx in non-transplant eligible second line or later patients with relapsedrefractory diffuse large B -cell lymphoma.

Source:

Abramson J, Ku M, Hertzberg M, et al. Glofitamab plus gemcitabine and oxaliplatin (Glofit-Gemox) for relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL): results of a global randomized phase III trial (STARGLO). Presented at the European Hematology Association 2024 Congress June 13-June 16, 2024. Madrid, Spain. Abstract LB3438