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Data from a phase III trial confirmed the benefit of glofitamab (Columvi) in relapsed or refractory diffuse large B-cell lymphoma (DLBCL), with the bispecific antibody improving overall survival (OS) over rituximab when either was added to chemotherapy.

In the so-called STARGLO trial, which involved patients not eligible for autologous stem cell transplant, median OS nearly doubled with glofitamab plus gemcitabine-oxaliplatin versus rituximab plus gemcitabine-oxaliplatin (25.5 vs 12.9 months).

Over a median follow-up of 20.7 months, the glofitamab regimen reduced the risk for death by 38% (HR 0.62, 95% CI 0.43-0.88, P=0.006), reported Jeremy Abramson, MD, of Massachusetts General Hospital and Harvard Medical School in Boston.

"Glofitamab is therefore the first CD20/CD3 bispecific antibody to demonstrate an overall survival benefit in a randomized phase III trial of diffuse large B-cell lymphoma," said Abramson at the annual European Hematology Association congress in Madrid.

Though the bispecific antibody was associated with a greater frequency of severe toxicities, progression-free survival (PFS) was also significantly improved in the glofitamab arm, at 13.8 months compared with 3.6 months in the rituximab arm (HR 0.40, 95% CI 0.28-0.57, P<0.000001), and more patients receiving glofitamab responded to therapy.

"We believe these results support the use of glofitamab-[gemcitabine-oxaliplatin] for the treatment of relapsed/refractory DLBCL," said Abramson.

Developed as a fixed-duration therapy, glofitamab is an off-the-shelf T-cell-engaging bispecific antibody. Phase I/II data showing high rates of complete response, with the majority lasting more than 2 years, formed the basis for the drug's accelerated approval last year, as a single-agent for relapsed/refractory DLBCL after two or more lines of therapy.

The current phase III study represents the confirmatory trial to support converting the accelerated approval to traditional approval, .

randomized 274 patients with relapsed or refractory DLBCL 2:1 to either glofitamab plus gemcitabine-oxaliplatin or rituximab plus the same chemotherapy backbone. Participants were required to have received at least one prior line of systemic therapy and had to be ineligible for autologous stem cell transplant.

They had a median age of 68 years, and the majority were male. Most (63%) had received one prior line of therapy with the remaining having received two or more prior lines. More than half had primary refractory disease. In the glofitamab arm, 39% relapsed on their last therapy and 61% were refractory, compared with 41% and 39% in the rituximab arm. Fewer than 10% of patients had prior exposure to CAR T-cell therapy.

In addition to the OS and PFS results described above, patients in the glofitamab arm were more likely to achieve an overall response (68.3%) or complete response (58.5%) compared with those receiving rituximab (40.7% and 25.3%, respectively).

An exploratory subgroup analysis showed that the OS results were generally consistent in favor of the glofitamab-based regimen, Abramson reported, though there were regional inconsistencies observed:

• Europe: HR 1.09 (95% CI 0.54-2.18)
• North America: HR 2.62 (95% CI 0.56-12.38)
• Rest of the world: HR 0.41 (95% CI 0.27-0.64)

"Interpretation of these subgroups is severely limited by extremely small patient numbers and very wide confidence intervals," he noted.

"Based on this observation, we did conduct a multivariable analysis including treatment arm, geographic region, and clinically relevant covariates, and found no association between geographic region and overall survival," Abramson said, adding that the analysis confirmed an OS benefit with the glofitamab regimen (HR 0.65).

The addition of glofitamab increased adverse events (AEs). Grade ≥3 AEs occurred in 77.8% of patients in the glofitamab arm versus 40.9% of those in the rituximab arm, with 47.2% and 22.7% considered related to either of the two agents specifically. Serious AEs were also more likely in the glofitamab arm (54.4% vs 17%), with 34.4% and 8% considered related to either agent.

In the glofitamab arm, AEs mostly included cytokine release syndrome (44.2%; with most grade 1/2, manageable, and reversible), cytopenias (neutropenia in 42.2% and febrile neutropenia in 3.3%), and infections (57.2%). As for other AEs of interest, neurological AEs occurred in 58.3% of patients in the glofitamab arm, immune effector cell-associated neurotoxicity syndrome in 2.3%, and tumor flare in 0.6%.

There was also a higher rate of fatal AEs in the glofitamab arm (8.3% vs 4.5%), "a difference that was largely driven by COVID-19," said Abramson.

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