Acalabrutinib Regimen Demonstrates Combinatorial Benefit in MCL

Prior to the FDA’s approval of acalabrutinib (Calquence) in combination with bendamustine and rituximab (Rituxan) in patients with mantle cell lymphoma (MCL), Tycel Phillips, MD, spoke with CancerNetwork® about the BTK inhibitor in the indicated patient population.

According to Phillips, an associate professor in the Division of Lymphoma, Department of Hematology and Hematopoietic Cell Transplantation at City of Hope in Duarte, California, the randomized, double-blind phase 3 ECHO trial (NCT02972840)found that progression-free survival (PFS) and overall survival (OS) data were improved by acalabrutinib in combination with bendamustine and rituximab vs chemotherapy alone when investigators censored for COVID-19 deaths, but that physicians should be wary because there is the possibility that the drug combination made patients’ COVID-19 worse.

Phillips compared the data of the ECHO study to those of the phase 3 SHINE study (NCT01776840), and mentioned that, in SHINE, it was clear that the drugs were more potent when combined vs when they were separated, and that the SHINE study had an increased toxicity profile. Philips said, “You don’t necessarily have the toxicity component with ECHO, but if you compare head-to-head, [the] ECHO [regimen] still probably doesn’t look any better than breaking these drugs apart.”

To conclude, he added that the ECHO regimen will be useful in patients with difficult-to-treat disease, and will likely see wider adoption, specifically, if some of the testing tools available in academic settings make their way into community settings.

Transcript:

You can view it through 2 lenses. In one sense, [the ECHO regimen] did meet its primary endpoint, which was a PFS benefit, and there was a hint that there was some trend toward an OS benefit, especially when they censored for COVID-19 deaths. On the flip side, for those COVID-19 deaths, you can’t rule out some contribution from the combination of the drugs making the infection worse in the patient population. There’s that part of the double-edged sword; [it’s] very similar to [the phase 3 SHINE study (NCT01776840)].

The biggest issue that you will always come across with the ECHO [regimen] and any of these [combination] therapies is: how does it compare if we were to give these medications separately? With these medications, they get bendamustine and rituximab for 6 months, and then they start the acalabrutinib, but they continue acalabrutinib indefinitely, until either disease progression or treatment intolerance.

Historically, how we would treat these patients is we would give them bendamustine, they would get maintenance with rituximab for approximately 2 years, and then at relapse, they would then start a BTK inhibitor. At least with the SHINE data set, it did not appear that that combination was more beneficial than [when the drugs were] sequential; additionally, the increased toxicity in the experimental arms led to the lack of uptake of SHINE.

You don’t necessarily have the toxicity component with ECHO, but if you compare head-to-head, [the] ECHO [regimen] still probably doesn’t look any better than breaking these drugs apart. In a more nuanced setting, you would probably reserve the ECHO regimen, meaning the bendamustine, rituximab, and acalabrutinib, for patients who had a more difficult disease to treat, and [there] probably shouldn’t be a one-stop [treatment] applied to everybody across the board. In certain situations, you probably won’t have access to certain distinguishing tests that will allow you to pick out these higher-risk patients who would benefit vs other patients. In some senses, I can see that this will eventually lead to the wider adoption of this across the board vs what may be the case if some of the testing that we do in academic sites were available to all community sites [where] we treat patients with [MCL].

Reference

FDA approves acalabrutinib with bendamustine and rituximab for previously untreated mantle cell lymphoma. January 16, 2024. Accessed January 16, 2024. https://shorturl.at/fTW0O