Zynlonta pushing into remission 2 other advanced lymphomas: Trials
Phase 2 studies treating high-risk follicular or marginal zone lymphoma
Treatment with Zynlonta (loncastuximab tesirine) is helping to push high-risk follicular lymphoma and marginal zone lymphoma into complete remission for a majority of the patients in either of two ongoing Phase 2 clinical trials led by the University of Miami.
An experimental treatment for either of these two typically slow-growing blood cancers, Zynlonta is approved in the U.S. and European Union to treat adults with diffuse large B-cell lymphoma or high-grade B-cell lymphoma that relapsed (came back) after or is refractory (didn’t respond) to two or more treatments.
People in the Phase 2 studies, both now recruiting eligible patients, also have relapsed or refractory disease. At least 67% of those treated to date have achieved a complete response, meaning their cancer was no longer evident on scans.
“We are excited about the complete response rate,” Izidore Lossos, MD, a professor at the University of Miami Miller School of Medicine, said in a university news story. “We are hoping this treatment will allow patients to live many more years than they used to be able to.”
Zynlonta works by targeting a protein on the surface of immune system B-cells
Follicular lymphoma and marginal zone lymphoma are blood cancers that begin in B-cells, a type of immune cell that normally produces antibodies to help in immune responses. Both usually have an indolent, or slow-growing, course. But these two lymphatic system cancers can progress, turning more aggressive and difficult to treat.
Zynlonta consists of an antibody designed to bind to CD19, a protein found on the surface of B-cells, that’s linked to a toxic chemical called SG3199. When the antibody binds to CD19, the chemical is taken up by B-cells and kills them. Their death is expected to reduce the size of tumors and, potentially, eliminate them entirely.
Juan Alderuccio, MD, a lymphoma specialist at the Sylvester Comprehensive Cancer Center, part of the university’s Miller School of Medicine, is leading the open-label Phase 2 clinical trial (NCT04998669) into Zynlonta, combined with rituximab (marketed as Rituxan, among other names), in people with relapsed or refractory follicular lymphoma and a high tumor burden.
Data reported covers the first 39 people, with a median age of 68, enrolled and treated. Most (92%) had aggressive cancer, and about half (51%) experienced disease progression within 24 months, or two years, of their first-line treatment.
Follicular lymphoma that’s progressing quickly is “a high-risk [disease] subtype … because at five years, the overall survival is 50%,” Alderuccio said in a video teaser for his presentation at the 2024 American Society of Hematology meeting, held Dec. 7–10 in San Diego and online.
The patients received 12 weeks of induction treatment with Zynlonta, given as an infusion into the bloodstream every three weeks, in addition to rituximab, given once weekly for four weeks, and then once every eight weeks. After this time, a maintenance regimen was initiated, based on each person’s response to treatment.
Complete responses seen in 67% and 70% of these advanced lymphoma patients
After the 12-week induction treatment, about two-thirds (67%) of the patients achieved complete response, with no signs of cancer. All but one (97%) had a complete or a partial response, the latter characterized by a significant reduction in tumor size or of the cancer’s spread within the body.
Most common treatment side effects were a rash that worsened with sun exposure, and edema, or swelling, which could be treated with diuretics. Severe side effects included low numbers of white blood cells, indicating a weakened immune system, and one serious case of fever.
Follicular cancer trial findings were described in the study “Loncastuximab tesirine with rituximab in patients with relapsed or refractory follicular lymphoma: a single-centre, single-arm, phase 2 trial,” published in The Lancet Haematology.
“The prognosis [outlook] for patients with relapsed or refractory follicular lymphoma has significantly improved over the last couple of years,” Alderuccio 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.”
This trial now is expanding to enroll up to 100 follicular lymphoma patients across multiple sites in the U.S. Because a majority of the initial 39 patients achieved a complete response by 12 weeks, trial researchers have shortened the treatment’s duration from 10 months to six.
The other open-label Phase 2 clinical trial (NCT05296070), led by Lossos, is testing Zynlonta alone in adults with relapsed/refractory marginal zone lymphoma, a rare lymphoma that often is overlooked in clinical studies. A total of 23 enrolled patients were given a Zynlonta infusion every three weeks for six cycles, with a total treatment duration of about 4.5 months. Most (91%) responded to the treatment, with 70% achieving a complete response.
This trial is enrolling up to 50 patients at its two open sites, the University of Miami and the City of Hope medical center in Duarte, California, and it may expand to three other sites.
About the Author
