Loncastuximab tesirine, an antibody-drug conjugate, is showing encouraging results in treating patients with relapsed or refractory follicular lymphoma (FL) and marginal zone lymphoma (MZL). Data from two clinical trials, presented at the American Society of Hematology (ASH) Annual Meeting, highlight the potential of this agent, both as a monotherapy and in combination with rituximab, to achieve high response rates in these challenging-to-treat patient populations.
Loncastuximab Tesirine Plus Rituximab in Follicular Lymphoma
A phase II clinical trial (NCT04998669) evaluated loncastuximab tesirine in combination with rituximab in 39 patients with relapsed or refractory FL. These patients often presented with high tumor burden or disease progression within 24 months (POD24) of initial treatment, factors associated with poorer prognoses. The study's primary endpoint was complete metabolic response (CMR) by week 12, assessed via PET/CT based on Lugano 2014 criteria.
The results demonstrated a 97.1% overall response rate (ORR) at week 12, with a 68.6% CMR rate. Notably, the combination showed similar response rates in patients with POD24, who have a 5-year survival rate of approximately 50%, compared to 85% for FL patients overall. With a median follow-up of 15.6 months, the 12-month progression-free survival (PFS) was 94.2% (95% CI: 78.7-98.5%), and the 12-month overall survival (OS) was 93.3% (95% CI: 75.6-98.3%).
"Even in patients with high-risk disease, this treatment is able to overcome adverse prognosis factors," emphasized Dr. Juan Alderuccio, lead study author and Associate Professor of Medicine at the University of Miami Miller School of Medicine.
The most common treatment-emergent adverse events included neutropenia (53.8%), elevated alkaline phosphatase (53.8%), anemia (46.1%), and maculopapular rash (46.1%). Grade ≥3 neutropenia occurred in 23.8% of cases. No treatment-related deaths were reported.
Loncastuximab Tesirine Monotherapy in Marginal Zone Lymphoma
In a separate ongoing multicenter phase II trial (NCT05296070), 23 patients with relapsed or refractory MZL received loncastuximab tesirine alone. MZL is a rare subtype of non-Hodgkin lymphoma, comprising only 6-8% of cases. The study revealed a 70% complete response rate and a 91% overall response rate. According to Dr. Izidore Lossos, Professor of Medicine and Chief of the Lymphoma Section at the Sylvester Comprehensive Cancer Center, the complete response rate is among the highest reported in any trial for this disease.
"We are excited about the complete response rate," underscored Dr. Lossos. "We are hoping this treatment will allow patients to live many more years than they used to be able to."
Clinical Implications
These findings suggest that loncastuximab tesirine, both as a single agent and in combination with rituximab, represents a promising treatment option for patients with relapsed or refractory FL and MZL. The manageable safety profiles and high response rates observed in these trials warrant further investigation in larger, randomized controlled studies. The relatively short treatment duration and low toxicity of the combination regimen may also improve patient compliance and quality of life.
