European researchers have proposed a biomarker-based treatment algorithm for patients with mantle cell lymphoma that could move treatment decisions beyond age and transplant eligibility toward individualized strategies based on disease biology and treatment response.
The call for a change to the status quo is timely because knowledge is expanding regarding biomarkers, said Ingrid Glimelius, PhD, who is first author of a review paper on the subject, published in The Lancet Haematology and a professor in the Department of Immunology, Genetics and Pathology at Uppsala University, Sweden.
She told Inside Precision Medicine: “We have had several novel drugs approved for mantle cell lymphoma in recent years, meaning we can offer different treatments to different patients. Previously, we had to rely on chemotherapy, but now we also have Bruton’s tyrosine kinase inhibitors and CAR T cells available, with bispecific antibodies in the pipeline.”
Mantle cell lymphoma is a lymph node cancer that has a varied clinical course ranging from indolent to highly aggressive. Historically, treatment stratification has relied on age and suitability for autologous stem cell transplantation, commonly using age 65 years as a cut-off, but the researchers say that this approach is increasingly inadequate as the field moves away from routine use of high-dose chemotherapy and transplantation.
Instead, they suggest that treatment should be guided by a combination of well-established molecular risk factors in mantle cell lymphoma. These include TP53 mutations (or p53 overexpression), markers of high cell division (Ki-67 ≥30% or ≥50%), the presence of a CDKN2A deletion, and disease biology (e.g., blastoid morphology). Dynamic markers of treatment response, such as measurable residual disease (MRD), clinical features, and computed tomography evaluation could then shape further treatment, the authors say.
Glimelius and team’s proposed algorithm divides patients into groups with low-, standard-, high-, and ultra-high-risk disease based on these biomarkers. For patients in the high- or ultra-high-risk categories, new targeted treatments and T-cell targeting immunotherapy, such as CAR T or bispecific monoclonal antibodies, may need to be used earlier in the course of the disease and be investigated as part of first-line therapy.
For patients with standard- or low-risk disease, the opposite approach could be used. For them, less intensive or entirely chemotherapy-free treatment could reduce the risk of side effects without being less effective.
“The goal is not for everyone to get more treatment,” said Glimelius. “On the contrary, risk adaptation is about providing the right treatment to the right patient. Those who have aggressive disease need to receive our most effective treatments earlier, but we should also avoid over-treating patients whose disease has a much more indolent course.”
However, Glimelius stressed that large, academic Phase III clinical trials are ideally needed before the proposed strategies are incorporated into clinical guidelines. Nonetheless, she hopes that the review paper raises awareness of biomarker stratified treatment for mantle cell lymphoma and starts conversation among experts at international meetings.
“This is not only important for the individual patient but also for the society and the use of resources in healthcare,” she said. “We think the time has come to move on from ‘one size fits all’ to a biologically tailored treatment for mantle cell lymphoma.”
