Two clinical trials testing the antibody loncastuximab tesirine (Zynlonta) showed encouraging results in patients with high-risk forms of two blood cancers—follicular lymphoma and marginal zone lymphoma.

The findings, led by physician-scientists at Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine, were presented at the American Society of Hematology's 2024 meeting in San Diego.

One study, a Phase II clinical trial led by Juan Alderuccio, M.D., a Sylvester haematologist and lymphoma specialist and associate professor of medicine at the Miller School, tested loncastuximab in combination with the antibody rituximab in 39 patients with relapsed or refractory follicular lymphoma who also had high tumour burden.

That study is also published Dec. 7 in the journal Lancet Haematology. Alderuccio is now expanding that study, which comprised all Sylvester patients, to include patients at multiple sites around the U.S. and to enroll a total of 100 patients.

The other study, led by Izidore Lossos, M.D., professor of medicine and chief of the lymphoma section of the division of haematology at Sylvester, tested loncastuximab alone in 23 patients with relapsed or refractory marginal zone lymphoma, a rare form of non-Hodgkin lymphoma, in an ongoing multi-centre Phase II trial.

Both studies showed encouraging results for the new treatment in these patient populations.

Because both of these cancers are typically slow-growing, both trials looked at overall response and complete response rates rather than survival rates.

For the follicular lymphoma trial, patients receiving loncastuximab and rituximab had a 67% complete response rate, meaning their cancer could no longer be detected by imaging, and an overall response rate of 97%—only one patient out of 39 had no response to the treatment.

In the marginal zone lymphoma trial, 70% of patients had a complete response and 91% had an overall response. As this trial is still ongoing, Lossos is presenting interim results at the conference.

Overcoming high-risk factors

Although these types of lymphoma are both typically indolent or slow-growing, patients with either type can see faster progression of their cancer and worse prognoses.

For the follicular lymphoma trial, Alderuccio and his colleagues enrolled patients whose cancer had not only relapsed or failed to respond to treatment but also showed a high disease burden or had seen progression of their disease within 24 months of their initial treatment, either of which carries a worse prognosis.

Follicular lymphoma patients with faster progression, known as POD24, have a five-year survival rate of only 50%, as compared to a survival rate of 85% for follicular lymphoma patients as a whole.

Most positively, 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.

"Even in patients with high-risk disease, this treatment is able to overcome adverse prognosis factors," Alderuccio said.

In the marginal zone lymphoma trial, the 70% complete response rate is the highest such rate in any trial for this cancer, Lossos said. Although this cancer is also slow-growing, relapsed patients rarely achieve complete response in other treatment settings.

Reducing side effects

Alderuccio noted that the treatment landscape for high-risk follicular lymphoma has changed dramatically just in the last few years. Patients now have many more treatment options than they once did.

"The prognosis for patients with relapsed or refractory follicular lymphoma has significantly improved over the last couple of years," he said. "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."

Although other treatment options also show high efficacy, the antibody combination pairs that high efficacy with a low burden of side effects and a short course of treatment. The main side effects seen in the trial were a rash that gets worse with sun exposure (patients are counselled to stay out of the sun during treatment) and fluid retention, which can be treated with diuretics.

Because so many patients saw a complete response by 12 weeks of treatment, the researchers also recently reduced the treatment length in their study from 10 to 6 months. Alderuccio hopes that the relatively short course of treatment combined with low toxicity will mean patients can carry out this treatment without difficulty. One of the patients who completed the treatment in the trial was 89 years old.

Options for a rare cancer

The marginal zone lymphoma trial is unique in that most clinical trials don't separate out patients with this type of cancer because it is relatively rare, comprising only 6 to 8% of non-Hodgkin lymphoma cases. Although other trials have included patients with this cancer, it can be hard to draw conclusions from those studies because the numbers of patients with marginal zone lymphoma are so low in any given trial, Lossos said.

Although it's an indolent disease with a median survival of 10 to 15 years, many patients need immediate treatment as the cancer can cause significant symptoms such as vision loss.

For most patients, even with treatment, they don't see their cancer die down—the complete response has to date been rare for this disease. That's why Lossos is optimistic about the 70% complete response rate seen so far in the ongoing trial, which has enrolled 23 patients out of a targeted 50. Currently, sites are open at the University of Miami and the City of Hope, and the researchers will soon expand that to five total sites.

"We are excited about the complete response rate," Lossos said. "We are hoping this treatment will allow patients to live many more years than they used to be able to."