Glofitamab is an investigational CD20xCD3 T-cell engaging bispecific antibody designed to target CD20 on the surface of B-cells and CD3 on the surface of T-cells. Moreover, glofitamab is part of Roche's larger bispecific antibody development program, which could lead to a new immunotherapy-based treatment for a variety of blood malignancies. According to the data presented at ASCO 2023, as of November 2022, 24 patients had enrolled and received study treatment (safety population). Out of 24 patients, 17 were efficacy evaluable. After a median follow-up of 5.1 months, the complete metabolic response rate was found to be 76.5% (13/17), followed by an overall response rate of 100%. 

In terms of safety results, grade ≥3 AEs occurred in 15 (63%) patients, and grade ≥3 AEs related to glofitamab occurred in 9 (38%) patients. In addition to that, serious AEs (SAEs) were reported in 12 (50%) patients, and SAEs related to glofitamab occurred in 4 (17%) patients. The median dose intensity was 100% for all  glofitamab + Pola-R-CHP components. Lastly, neutropenia was reported in 12 (50%) patients, followed by febrile neutropenia in 2 (8.3%) patients and grade 3/4 infection in 4 (17%) patients.

KOL insights

“Overall, the safety profile is favorable, and there were no specific higher-grade toxicities related to glofitamab.” –Expert Opinion.

Conclusion

DLBCL is the most common type of NHL that affects B-lymphocytes and comprises 30–40% of adult NHL. The American Cancer Society also states that the most common kind of NHL in the United States is DLBCL, accounting for about one out of every three lymphomas. Overall, NHLs have an annual incidence of 15–20 cases/100,000 in the United States. In addition to that, DLBCL accounts for approximately 31% of all NHLs in Western countries and 37% of B-cell tumors worldwide. According to the Surveillance, Epidemiology, and End Results (SEER), using statistical models for analysis, rates for new DLBCL cases have been falling on average by 0.9% each year over the last 10 years (2007–2016). As we know, R-CHOP has been the standard-of-care regimen for first-line DLBCL for over 20 years. This has occurred despite several randomized controlled trials in this setting looking at ways to improve upon R-CHOP, including regimens that intensified therapy regimens and substituted other agents. Recently, in April 2023, the US FDA approved POLIVY + R-CHP for previously untreated DLBCL. Somewhere after this approval, if we compare them to other emerging therapies that are being investigated as first-line treatment choices for DLBCL, POLIVY is likely to have an edge over rivals in terms of gaining more patients and market share. POLIVY + R-CHP has also shown a significant PFS benefit versus R-CHOP as 1L therapy for DLBCL. Apart from that, many other emerging drugs that are being evaluated in monotherapy or combination will give net-to-net competition  to each other once they get approved in the first line setting.

Based on the above findings of glofitamab + Pola-R-CHP, it can be assumed that the encouraging results of glofitamab + Pola-R-CHP suggest a promising avenue for outpatient treatment in untreated DLBCL patients