mantle lymphoma |Mantle lymphoma: Efficacy of a 2nd generation inhibitor of crude tyrosine kinase

Mantle lymphoma: Efficacy of a 2nd generation inhibitor of crude tyrosine kinase



Acalabrutinib, a highly selective inhibitor of crude tyrosine kinase, shows a net benefit in relapsed or refractory mantle lymphomas.

Mantle cell lymphoma is a particularly aggressive type of non-Hodgkin's lymphoma. It represents 3 to 10% of all non-Hodgkin lymphomas. Crude tyrosine kinase is a particularly interesting target in this condition and has renewed the treatment of these forms of leukemia.

Treatment with acalabrutinib gives a high rate of durable responses and a favorable tolerance profile in patients with recurrent or refractory mantle cell lymphoma.

These are the results of a study published in the Lancet, an open and non-comparative study, which resulted in September obtaining accelerated approval in the United States by the Food and Drug Administration (FDA) in the "treatment of adults With mantle cell lymphoma that have received at least one previous treatment. "

An uncontrolled study
This accelerated approval was obtained while the study is still preliminary: This is a Phase 2 open and non-comparator clinical trial on 124 patients with recurrent or refractory mantle cell lymphoma.

Acalabrutinib was administered orally (100 mg twice daily) until disease progression or unacceptable toxicity. The main criterion for judging the result was the overall response assessed according to the current classification, which is the Lugano classification.

Particularly interesting improvement
The patients (median age 68 years) received on average two previous treatments. During the 15.2 month evaluation, 100 patients (81%) received a comprehensive response and 49 (40%) received a complete response!

With similar results, the medians estimated for the duration of the response, progression-free survival, and overall survival were not reached at 12 months: 72%, 67%, and 87%, respectively.

Side effects that remain moderate
The most common side effects are mainly moderate (grade 1 or 2 on a gradation to 4) and are headaches (38%), diarrhea (31%), fatigue (27%) and muscle aches (21%).

The most common adverse events of Grade 3 are neutropenia (10%), anemia (9%) and pneumonia (5%). There have been no cases of atrial fibrillation and one case of grade 3 hemorrhage or worse. Treatment was interrupted in 54 patients (44%), mainly due to an evolutionary disease (31%) or adverse events (6%).

Lymphoma is a blood disease
Lymphoma is a cancer of the lymphatic system characterized by the uncontrolled growth of abnormal white blood cells that are usually responsible for controlling infections: lymphocytes.
When these lymphocytes become abnormal, they develop uncontrolledly in lymphoid organs that are located in many organs of the body (lung, liver, intestine) in addition to the lymphoid organs: lymph nodes, spleen, bone marrow, thymus. Due to the role of the lymphatic system in immune defenses, lymphoma will be accompanied by an immune deficiency.

Further studies
It is rather unusual to obtain accelerated approval with an open and non-comparative study of the reference molecule, but the results are very interesting.
Acalabrutinib is a second-generation crude tyrosine kinase (BTK) inhibitor that is more selective for targeting alternative kinases than ibrutinib (first-generation IBTK).

As a drug that has received accelerated approval in the United States, the acalabrutinib has yet to undergo further, broader and comparative studies to verify these excellent results.