Use of BTK Inhibitors in the First-Line Mantle Cell Lymphoma Treatment Landscape

At the 2023 Lymphoma, Leukemia & Myeloma Congress in New York, New York, Jia Ruan, MD, PhD, Weill Cornell Medicine, New York, New York, speaks on the inclusion of Bruton’s tyrosine kinase (BTK) inhibitors in the first-line mantle cell lymphoma (MCL) treatment space, highlighting findings from studies such as the TRIANGLE and SHINE trials. 

Transcript:

Hi, my name is Dr. Jia Ruan. I'm a lymphoma [clinician] attending at Weill Cornell New York Hospital. I take care of patients with a number of different types of lymphomas, and I'm actually here attending the Lymphoma, Leukemia [& Myeloma] Conference in New York City. 

Now that we have a lot of novel agents and they're very active and have been practiced in the relapsed/refractory settings, we're finding ways of working with investigational, inter-group studies and investigator-initiated studies to try to incorporate those novel agents into our frontline therapy. They can be combined with chemoimmunotherapy or they can be just be chemotherapy-free altogether.

I want to give some examples [of] those approach[es] We talked about the high-intensity regimen of [rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone] (R-CHOP), [rituximab, dexamethasone, cytarabine, and cisplatin] (R-DHAP) induction and consolidation. Now there's a study called the TRIANGLE study, which is conducted by the European Mantle Cell Network where a BTK inhibitor, which [is] the novel agent is being incorporated into the induction and maintenance sequence of the treatment regimen. That combination has shown to have a better progression-free survival with preliminary data. 

Also, very interestingly, I think it's quite important that another way of looking [at] novel agents was introducing the ibrutinib in the induction, but to get rid of the autologous stem cell transplant as consolidation, which would be huge news, I guess, and very much welcomed from a patient standpoint. That particular experimental arm also seems to be doing quite well. In fact, the autologous stem cell transplant, the traditional arm, did not seem to be doing better. So, we feel optimistic---cautiously optimistic---that transplant consolidation may be safely omitted while being replaced by the incorporation of BTK inhibitors, induction, and maintenance.

Likewise, I think similar studies or research with BTK inhibitor addi[tion] to the bendamustine-rituximab (BR) induction and maintenance backbone is also being conducted in patients who [are] more elderly and less fit, so they're not transplant candidates. We have the study results from the SHINE randomized phase 3 study, and the addition of ibrutinib to BR induction and rituximab maintenance seems to increase the median progression-free survival by 28 months. 

Th[is] data [is] being discussed and digested, and figured how to be introduced into our clinical practice. There is concern also for side effect profiles. The addition of ibrutinib to the bendamustine arm seems to have more patients discontinue treatment due to side effects. So, we're hopeful that some other newer studies such as the ECHO study, which is also a randomized phase 3 study, that [is] looking at acalabrutinib instead of ibrutinib, but onto the same induction and maintenance backbone, perhaps would give us newer data. 

We're hopeful that it would come with, hopefully, a better safety profile and would be more encouraging to use that upfront in patients who are not transplant candidate[s].

Source: 

Ruan J. Initial Therapy for Mantle Cell Lymphoma. Presented at Lymphoma, Leukemia & Myeloma Congress; October 18-21, 2023. New York, NY