The antibody loncastuximab tesirine may offer a benefit in patients with high-risk follicular lymphoma and marginal zone lymphoma, according to the findings of two clinical trials presented by Alderuccio et al and Lossos et al at the 2024 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstracts 337 and 3032) and simultaneously published in The Lancet Haematology.
“The prognosis for patients with relapsed or refractory follicular lymphoma has significantly improved over the last couple of years,” explained lead study author of the first trial, Juan Alderuccio, MD, Associate Professor of Medicine at the University of Miami Miller School of Medicine as well as a hematologist and lymphoma specialist at the Sylvester Comprehensive Cancer Center. “We have several options, and our goal now is to keep high efficacy but also decrease toxicity. And that’s what we’re trying to do now,” he added.
Although marginal zone lymphoma has a median survival of 10 to 15 years, many patients need immediate treatment because the cancer may cause significant symptoms such as vision loss. Even with treatment, a majority of patients may not see their cancer diminish. Complete response has been rare in this cancer type.
First Study Methods and Results
In the first study, a phase II clinical trial, researchers assigned 39 patients with relapsed or refractory follicular lymphoma to receive loncastuximab tesirine in combination with the antibody rituximab. The researchers enrolled patients whose cancer had not only relapsed or failed to respond to treatment but also showed a high tumor burden or had seen progression of their disease within 24 months of their initial treatment, either of which may worsen prognoses. The patients with faster disease progression, known as POD24, have a 5-year survival rate of 50% compared with 85% among the patients as a whole.
The researchers found that the patients receiving loncastuximab tesirine and rituximab had a 67% complete response rate and an overall response rate of 97%. One of the patients had no response to the treatment. Of note, the antibody combination showed similar response rates in patients with POD24 and those without, each of which made up roughly half the patients in the trial.
Although other treatment options have shown high efficacy, the antibody combination appeared to pair high efficacy with a low burden of side effects and a short course of treatment. The main side effects experienced in the trial were a rash that worsened with sun exposure and fluid retention, which could be treated with diuretics.
Because so many of the patients achieved a complete response by 12 weeks, the researchers also recently reduced the treatment length in their study from 10 to 6 months. The researchers hope the relatively short course of treatment combined with low toxicity will allow patients to receive it without difficulty. For instance, one of the patients who completed the treatment in the trial was 89 years old.
The researchers of the first trial are currently expanding the trial to include patients at multiple sites across the United States and to enroll a total of 100 patients.
Second Study Methods and Results
In the second study, an ongoing multicenter phase II trial, researchers assigned 23 patients with relapsed or refractory marginal zone lymphoma to receive loncastuximab tesirine alone. The researchers discovered that 70% of the patients had a complete response, and 91% of them had an overall response. They noted that the complete response rate was among the highest in any trial for this disease. Patients with relapsed marginal zone lymphoma rarely achieve complete response in other treatment settings.
The researchers stressed that most clinical trials don’t separate out patients with this type of cancer because it is relatively rare, comprising just 6% to 8% of non-Hodgkin lymphoma cases. Although other trials have included patients with this cancer type, it is often challenging to draw conclusions from those studies because the numbers of patients with marginal zone lymphoma are low in any given trial.
Currently, sites are open at the University of Miami and City of Hope, and the researchers plan to expand the total to five sites.
Conclusions
The researchers highlighted that both studies showed encouraging results for the novel treatment in their respective patient populations. Because both cancer types typically grow slowly, both trials assessed overall response and complete response rates rather than survival rates.
“Even in patients with high-risk disease, this treatment is able to overcome adverse prognosis factors,” emphasized Dr. Alderuccio.
“We are excited about the complete response rate,” underscored lead study author of the second trial, Izidore Losses, MD, Professor of Medicine and Chief of the Lymphoma Section of the Division of Hematology at the Sylvester Comprehensive Cancer Center. “We are hoping this treatment will allow patients to live many more years than they used to be able to,” he concluded.
Disclosure: For full disclosures of the study authors, visit ash.confex.com, ash.confex.com, and thelancet.com.
