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ASH 2025: Milder chemo works for rare, aggressive lymphoma

9 Dec 2025
ASH 2025: Milder chemo works for rare, aggressive lymphoma

Most patients with a rare and aggressive form of large B-cell lymphoma can safely receive a less toxic treatment than the intensive chemotherapy often used, according to new research from Sylvester Comprehensive Cancer Centre, part of the University of Miami Miller School of Medicine.

Lead researcher Juan Alderuccio, M.D., a haematologist and lymphoma specialist at Sylvester, presented this research at the American Society of Haematology meeting in Orlando.

The study’s findings could help standardise treatment for T-cell/histocyte-rich large B-cell lymphoma (THRLBCL) — a crucial step toward ensuring patients receive the most effective, least toxic care.

“Until this study, we didn't know exactly how to treat this disease,” Alderuccio said of THRLBCL.

In the absence of a formal standard of care, physicians have been treating newly diagnosed patients with a variety of approaches.

“Our aim was to identify the best first-line treatment considering patient and disease characteristics,” he said.

The study’s results indicate that most patients should receive a combination regimen known by the acronym R-CHOP, which is already established as an effective treatment for the most common type of large B cell lymphoma.

Previous research has suggested that patients with THRLBCL benefit from intensive chemotherapy regimens.

However, this approach comes with a significant downside: frequent and considerable side effects.

One study documented more infections, nerve pain, inflammation in the digestive tract and dangerously low levels of white blood cells in patients who received more intensive chemotherapy regimens than in those given R-CHOP.

To determine if R-CHOP could offer similar benefits without these drawbacks, the researchers compared results in THRLBCL to those of a cohort of patients with diffuse large B cell lymphoma (DLBCL), the most common large B cell lymphoma.

THRLBCL tends to affect younger patients, especially men, who are often diagnosed at later stages in the cancer’s progression.

THRLBCL patients have fewer malignant B cells than their counterparts and more immune suppression, which benefits the cancer.

This disease is also prone to spread to other organs, including the liver, lungs and bone marrow.

It is also much less common. An analysis of patient data in the U.S. National Cancer Data Base counted 622 cases of THRLBCL from 2010 to 2015 and 91,588 cases of diffuse large B cell lymphoma for that period.

With so few patients, researchers have difficulty running the clinical trials typically used to establish standardised approaches to care, according to Alderuccio.

In the absence of this guidance, some oncologists turn to intensive chemotherapy, others use bone marrow transplantation, and still others administer R-CHOP.

The latter regimen combines three chemotherapy drugs (cyclophosphamide, doxorubicin, vincristine), a steroid (prednisone) and the monoclonal antibody rituximab, which latches onto the CD20 protein on B cells.

R-CHOP has proven highly effective in treating DLBCL.

About 60% of these patients see their cancer disappear after completing the six cycles of R-CHOP.

For the study, Alderuccio and colleagues drew on three sources.

They used data from THRLBCL patients collected by the Lymphoma Epidemiology of Outcomes consortium, which includes the University of Miami and seven other U.S. academic centres, and from the Czech Lymphoma Study Group in the Czech Republic.

They compared these patients’ survival to that of their counterparts with DLBCL, data they obtained from these datasets, plus the Iowa University/Mayo Clinic Molecular Epidemiology Resource.

Of the 140 patients with THRLBCL, 106 received R-CHOP.

Four years following treatment, 80% of these patients were still alive and 70% had not had their cancer return or experienced complications.

The nearly 6,100 patients they included with diffuse large B cell lymphoma had similar outcomes.

In fact, a statistical testing called propensity score matching showed no difference between the two, Alderuccio said.

Meanwhile, intensive chemo regimens did not appear to improve the THRLBCL patients’ survival.

Next, he and his colleagues are expanding the study to include more patients from three new sources: the U.S. Department of Defence; the Veterans Administration registry; and a nationwide Danish cohort.

Through this follow-up research, they hope to identify THRLBCL patients for whom R-CHOP is likely to fail, with the ultimate goal of conducting a clinical trial to assess alternatives for them.

Source: University of Miami Miller School of Medicine