At the 2023 European Hematology Association (EHA) Congress, Vincent Ribrag, MD, Institut Gustave Roussy, Villejuif, France, participated in a debate about if Bruton's tyrosine kinase (BTK) inhibitors should be combined with other therapies, such as bendamustine and rituximab, as first-line treatment for patients with mantle cell lymphoma (MCL). 

Transcript: 

My name is Vincent Ribrag. I'm working at Gustave Roussy Institute [in] Villejuif, France, and I am working on drug development in our drug department. I've done a discussion on [whether we should] have to treat patients with mantle cell lymphoma with [Bruton's tyrosine kinase] (BTK) inhibitor[s] in first-line. I had to [argue] against. 

The main message that we discussed was not on the role of BTK inhibitors in mantle cell lymphoma, because it's a breakthrough and it's clearly a key drug for patients with mantle cell lymphoma. The discussion was about when to give it. Is it first-line, [or] is it second-line? 

The discussion was about 2 main clinical trials. [The first] material that has been published in the New England Journal of Medicine was the SHINE trial. The SHINE trial compared a commercial arm, we can say, with bendamustine, rituximab, and maintenance rituximab, to an experimental arm. We used bendamustine, rituximab and ibrutinib.

There was a crossover. Patients who received ibrutinib at first-line of course have not to crossover, but the commercial arm may receive ibru[tinib] at progression or relapse. This trial reached its primary endpoint. There was clearly a benefit of the comb[ination] for ibrutinib in the experimental arm. Concerning [progression-free surivival] (PFS) but not to all survival, with toxicities that impact the overall survival in this experimental arm. The discussion is still open, because this trial was not really conclusive on overall survival. 

But, this trial reached the primary PFS endpoint, and there [are] still some discussions, because patients received at progression, and [were] able to deliver very good overall survival. [This] was debated by my colleague from [the] Netherlands, who presented the preliminary results from the TRIANGLE trial, [and] showed that the ibru[tinib] arm with a shot for up  could even spare the ibru[tinib] dose chemotherapy with autologous stem cell transplant in first-line, but the results are not mature enough.

The question remains, do we have to use BTK inhibitors? The answer is clearly yes. Do we have to use it in first-line in combo with bendamustine and rituximab? The answer is not so easy. Just to remind [you] that the SHINE trial is not comparing testing ibru[tinib] alone—a BTK inhibitor alone—but a comb[ination] with bendamustine and rituximab. It is the comb[ination] that was clearly toxic.

In [this] perspective, we can think that we may have data with other combination[s] and BTK inhibitor in first-line, or that with other BTK inhibitors in first-line to be sure that we have thought to use it commonly with chemo[therapy]. The TRIANGLE trial from the European MCL Network has positive results now, concerning the fact that you can use ibru[tinib] rather than high-dose chemotherapy. But, as I mentioned previously, [the] results are not mature. Thank you.

Source: 

Ribrag V, et al. Should BTK inhibitors be used in 1st line treatment in MCL? Against. Presented at the EHA Congress; June 8-15, 2023; Frankfurt, Germany.