BTK Inhibitors and Mantle Cell Lymphoma: Benefits and Risks of Treatment

New research has demonstrated the importance for understanding risks of bleeding, cardiovascular issues, nonadherence (due to the twice a day dosing), as well as gastrointestinal AE’s when deciding to use Bruton’s tyrosine kinase inhibitors (BTK) for mantle cell lymphoma (MCL) patients. However, as a whole, they are recommended for MCL patients.

BTK Inhibitors

Previously, second-line treatment of BTK inhibitors was initiated following evaluation of the response to front-line therapy. But guidelines now demonstrate that either lenalidomide-based treatment or BTK inhibitors for relapsed/refractory MCL patients should be used as a second-line therapy for all patients.
As BTK’s are typically overly expressed in MCL, inhibiting them can lead to improved survival.
Overall BTK inhibitors have demonstrated promise in effectiveness. Further, they have been associated with few AE’s.

Ibrutinib

Ibrutinib is an oral inhibitor which has been developed for adult patients who have had at least one other prior treatment.

Phase 2 and Phase 3 trials have demonstrated that progression free survival with treatment of ibrutinib was 12.8 months and the overall survival was 25 months. The ORR across the trials was 66%. As with many treatments, the earlier the treatment started, the better outcomes the patient experienced.

In a pooled analysis over 7 years, there were not any unexpected late toxicities. 15 to 20% of patients did experience a hematologic toxicity such as anemia, neutropenia, and thrombocytopenia. Other toxicities include diarrhea, atrial fibrillation, and bleeding.

Additionally, primary and secondary resistance to this treatment sometimes occurred and is not yet understood.

FDA Approved BTK Inhibitors

As of now, there are two second-generation BTK inhibitors which are FDA approved. These are zanubrutinib and acalabrutinib. Each of these have demonstrated similar efficacy results as ibrutinib. However, unlike ibrutinib, these therapies are capable of binding to CC481 as well as C481S residues.

As such, these therapies have fewer toxicities associated than ibrutinib.

Toxicities for these therapies included diarrhea, cardiac AEs, hypertension, and bleeding.

You can read more about these therapies here 

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