Today, treatment decisions for patients with mantle cell lymphoma are heavily based on age alone, although the disease can range from slow-growing (indolent) to very aggressive. In a new journal article, Ingrid Glimelius and co-authors suggest that it is time to let the disease's biology also guide the treatment – and to provide more effective interventions earlier for those at the highest risk of aggressive disease, while avoiding unnecessarily intensive treatment for patients with indolent disease.
Mantle cell lymphoma is a form of lymph node cancer with a widely varying course. Some patients can live for a long time with a slow-growing or indolent form of the disease, while others may relapse early despite intensive treatment.
Traditionally, the choice of treatment has been primarily determined by the patient's age and whether the person can cope with intensive chemotherapy and stem cell transplantation. But in recent years, knowledge of the biology of the disease has increased significantly, while many new targeted treatments and immunotherapies have also become available.
High-risk patients can be identified at the time of diagnosis
In an overview article in the journal The Lancet Haematology, Ingrid Glimelius and co-authors argue that these biological characteristics and availability of new therapies ought to change how treatment is planned right from the time of diagnosis.
"We still treat patients as if mantle cell lymphoma is one homogenous disease, even though we know today that there are very big biological differences. We can now identify patients who are at very high risk of relapse and dying from the disease right at the time of diagnosis. So it's reasonable to ask why they should receive the same treatment as patients whose disease is far more slow-growing," says Ingrid Glimelius.
Among the most important markers of high-risk disease are changes in the tumour suppressor gene TP53, high cell division measured by Ki-67, and blastoid morphology. Testing for residual tumour cells after treatment, known as measurable residual disease, can provide additional information on how well an individual patient's disease has responded to treatment.
The authors propose a future treatment concept where patients are divided into groups with low, standard, high and ultra-high risk disease. 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.
Avoiding over-treatment of low-risk group
For patients with indolent 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. 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," says Ingrid Glimelius.
The authors emphasise that several of the proposed strategies need to be tested in clinical trials before they can become a new standard. But according to them, our knowledge in biology has reached a point where future studies and treatment guidelines should no longer be based primarily on the patient's age.
"We think the time has come to move on from 'one size fits all' to a biologically tailored treatment for mantle cell lymphoma," Ingrid Glimelius concludes.
