A novel treatment regimen with the bispecific antibody glofitamab has demonstrated improvements in survival outcomes for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), according to data presented at the European Hematology Association (EHA) 2024 Congress.¹

The phase III STARGLO trial evaluated the efficacy and safety of glofitamab plus gemcitabine and oxaliplatin compared with rituximab plus gemcitabine and oxaliplatin in patients with DLBCL who had received at least one prior line of therapy. The results showed a near doubling of median overall survival and a 38% reduction in the risk of death (hazard ratio [HR] = 0.62, P = .006). Authors of the study noted that the addition of glofitamab to gemcitabine and oxaliplatin may become a new standard of care for patients who have limited treatment options, particularly those who are ineligible for chimeric antigen receptor (CAR) T-cell therapy or autologous stem cell transplantation.

“Glofitamab is the first CD20 x CD3 bispecific antibody to demonstrate an overall survival benefit in DLBCL in a randomized phase III trial,” said lead study author Jeremy S. Abramson, MD, of Massachusetts General Hospital Cancer Center, Boston. “We believe these results support the use of glofitamab [in combination with gemcitabine and oxaliplatin] as a new, off-the-shelf treatment for relapsed or refractory DLBCL in patients who are transplant-ineligible in the second-line or later setting.”

Jeremy S. Abramson, MD

As Dr. Abramson noted, glofitamab is a CD20 x CD3 bispecific antibody that is well tolerated with durable responses when given as fixed-duration monotherapy in relapsed or refractory DLBCL after at least two prior lines of therapy.²

Study Methods

For the phase III STARGLO trial, Dr. Abramson and colleagues enrolled 274 patients, randomly assigned in a 2:1 ratio to receive either glofitamab plus gemcitabine and oxaliplatin or rituximab plus gemcitabine and oxaliplatin. Patients given the glofitamab regimen received eight cycles of the combination therapy, followed by four cycles of glofitamab monotherapy. The randomization was stratified based on the number of prior therapies (one vs two or more) and whether patients were refractory to their last treatment.

Before glofitamab was initiated, patients received pretreatment with the monoclonal antibody obinutuzumab. During the first cycle, glofitamab was administered in weekly step-up doses of 2.5 mg and 10 mg. From the second cycle onward, patients received a target dose of 30 mg every 21 days.

Patients who had only one prior therapy were included if they were ineligible for autologous stem cell transplantation. This ineligibility was determined based on factors such as age (70 years or older), organ dysfunction, Eastern Cooperative Oncology Group performance status of 2 or higher, patient refusal of transplantation, or other investigator-assessed comorbidities.

The primary endpoint of the study was overall survival. Secondary endpoints included progression-free survival and complete remission rate, both assessed by an independent review committee.

Key Results and Safety Profile

With a median follow-up of 20.7 months, the median overall survival for patients treated with glofitamab plus gemcitabine and oxaliplatin was 25.5 months, compared with 12.9 months for those receiving rituximab plus gemcitabine and oxaliplatin. Progression-free survival was also significantly improved with glofitamab plus gemcitabine and oxaliplatin, reaching 13.8 months vs 3.6 months with rituximab plus gemcitabine and oxaliplatin (P = .0001), which translates to a 60% reduction in the risk of disease progression or death (HR = 0.40). Additionally, the complete response rate more than doubled with glofitamab plus gemcitabine and oxaliplatin, reaching 58.5% compared with 25.3% with rituximab plus gemcitabine and oxaliplatin.

The safety profile of glofitamab plus gemcitabine and oxaliplatin was generally consistent with expectations, said Dr. Abramson, although it did yield an increase in serious adverse events compared with the rituximab combination regimen (54.4% vs 17.0%). However, Dr. Abramson reported, patients given glofitamab plus gemcitabine and oxaliplatin received a median of 11 treatment cycles, compared with 4 cycles for those given rituximab plus gemcitabine and oxaliplatin arm, which may partly explain this difference.

Cytokine-release syndrome occurred in 44.2% of patients receiving glofitamab plus gemcitabine and oxaliplatin but was considered to be mostly mild to moderate. There was also a higher rate of fatal adverse events with the glofitamab regimen (8.3% vs 4.5%), according to Dr. Abramson, who noted this was largely driven by COVID-19 infections. A protocol amendment requiring a negative COVID-19 test before enrollment and discontinuation of protocol therapy in the event of a positive test eliminated further COVID-19–related fatal adverse events.

Expert Point of View

Joshua D. Brody, MD, Director of the Lymphoma Immunotherapy Program at the Icahn School of Medicine at Mount Sinai, New York, underscored the transformative potential of the STARGLO trial results. They suggest the combination of glofitamab with gemcitabine and oxaliplatin may significantly alter the treatment landscape for relapsed or refractory diffuse large B-cell lymphoma, offering a more effective option for patients who have limited alternatives.

Joshua D. Brody, MD

“The STARGLO results are impressive and immediately practice-changing,” Dr. Brody told The ASCO Post. “Overall survival benefits are the gold standard of clinical trial results, and in this case, that added efficacy was achieved with almost comparable safety—a real win-win result.”

Key Role for Bispecific Antibodies in Lymphoma

“Any patient who is being considered for standard gemcitabine and oxaliplatin chemotherapy (a very common second- and third-line therapy) should now have a CD20 x CD3 bispecific antibody added to that regimen,” Dr. Brody added, noting this impact could potentially be extrapolated to similar clinical situations.

According to Dr. Brody, bispecific antibodies for lymphoma have evolved from “just another option that appeared better and safer than alternatives” to “unquestionably helping patients to live longer.” He anticipates increased adoption of these agents among both academic and community oncologists.

Looking ahead, Dr. Brody also pointed to ongoing research exploring the potential of bispecific antibodies in first-line treatment. “The biggest unanswered question now is whether CD20 x CD3 bispecific antibodies can combine as powerfully with first-line chemotherapy (eg, R-CHOP [rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone]) as they do here with salvage chemotherapy,” he concluded. “Those trials are ongoing, and, I’d say, they are extremely likely to succeed.”

DISCLOSURE: Dr. Abramson has served as a consultant or advisor to Roche, AbbVie, ADC Therapeutics, AstraZeneca, BeiGene, BMS, Cellectar Biosciences, Caribou Biosciences, Celgene, Genentech, Gilead Sciences, Incyte, Interius BioTherapeutics, Janssen, Lilly, Novartis, Seagen, and Takeda and has received research funding from BMS, Cellectis, Merck, Mustang Bio, Regeneron, and Seagen. Dr. Brody has served as a consultant or advisor to ADC Therapeutics, Epizyme, and Seagan and has received research funding from BMS, Kite/Gilead, and Merck.

REFERENCES

1. Abramson J, Ku M, Hertzberg M, et al: Glofitamab plus gemcitabine and oxaliplatin for relapsed/refractory diffuse large B-cell lymphoma: Results of a global randomized phase III trial (STARGLO). EHA 2024 Congress. Abstract LB3438. Presented June 15, 2024.

2. Dickinson MJ, Carlo-Stella C, Morschhauser F, et al: Glofitamab for relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med 387:2220-2231, 2022.