Diffuse large B-cell lymphoma (DLBCL) often strikes patients in their 70s and 80s, many of whom are too frail for the aggressive chemotherapy that defines the standard of care. For decades, fit older patients received R-CHOP, while unfit patients were offered reduced-dose regimens such as R-mini-CHOP. But experts say these compromises remain inadequate: as Dai Chihara, MD, PhD, of MD Anderson Cancer Center, told MedPage Today, the 50% dose of standard chemotherapy "produces a suboptimal response and outcome," with roughly one in four patients failing to complete six cycles due to infections or poor tolerance.
Bispecific antibodies are emerging as a more potent alternative. In a phase II study of the combination rituximab, polatuzumab vedotin, and glofitamab, overall response rates ranged from 90% to 96% in elderly, unfit, or frail patients (median age 80), with 1-year progression-free survival of 85% and overall survival of 90%. Another trial testing epcoritamab with rituximab and attenuated chemotherapy reported a complete response rate of 86% and a 1-year PFS of 94.7%. As monotherapy, epcoritamab and mosunetuzumab produced overall response rates of 70% and 73.5%, respectively, in patients with a median age around 82.5.
Experts caution that bispecifics carry their own toxicities, including cytokine release syndrome, neurotoxicity, and immunosuppression. While many side effects appear age-agnostic, infections remain the key unsolved problem. "A majority of bad outcomes and deaths have been because of COVID or respiratory infections," noted Pallawi Torka, MD, of Memorial Sloan Kettering Cancer Center. Still, she called the results "almost in the curative realm," adding that durable remissions could "bridge that gap between age and fitness and cure" if infection risk can be managed.