Acalabrutinib/Chemotherapy Poised to Be Effective in High-Risk MCL

Tycel Phillips, MD, an associate professor in the Division of Lymphoma, Department of Hematology and Hematopoietic Cell Transplantation at City of Hope in Duarte, California, spoke with CancerNetwork® before the FDA’s approval of acalabrutinib (Calquence) with bendamustine and rituximab (Rituxan) in patients with mantle cell lymphoma (MCL) and emphasized that the combination will be effective in high-risk patients.¹

Patients with TP53 mutations, blastoid and/or pleomorphic histology, complex cytogenetics, and a high proliferative index were among the high-risk patients he listed and explained that acalabrutinib combined with bendamustine and rituximab would be more beneficial then chemotherapy alone.

The randomized, double-blind phase 3 ECHO trial (NCT02972840) found that progression-free survival (PFS) was notably improved in the acalabrutinib combined with chemotherapy group vs the chemotherapy alone group at 66.4 months vs 49.6 months, respectively.² Phillips also stated that he would be “hard-pressed” to give a standard patient with MCL the combination regimen because many of those patients have been proven to get durable responses from chemotherapy alone.

Transcript:

We’re coming back to these high-risk patients—these patients with TP53 mutations, patients who are blastoid [and/or] pleomorphic, patients with complex cytogenetics, patients with high proliferative [index]. The patients with high proliferative [index] can be identified by random standard testing and blastoid [and/or] pleomorphic [status] is something that a pathologist can identify. Complex cytogenetics and TP53 mutations may not be something that can be readily picked up or tested for in some sites.

In those patients, this combination of acalabrutinib plus bendamustine and rituximab would be better than giving bendamustine alone. That would fix some of that high-risk patient population need, which has been a struggle in the community space.

This will be something that we potentially utilize in some of these higher-risk patient populations, especially the elderly patient population, because these are patients who, historically, may have just [received] a BTK inhibitor alone. Ideally with the safety aspect of the ECHO study, we would consider giving bendamustine with acalabrutinib because it would give us a longer [PFS] than what we would get with any of these drugs by themselves. Outside of that, if you had a run-of-the-mill, standard-risk [patient with] MCL, [I’d be] hard pressed to say that this ECHO regimen would be appropriate for those patients, given that a lot of these patients would still get very durable response with chemotherapy alone, and then would have some time off of treatment before we even started a BTK inhibitor in the second-line space.

References

1. FDA approves acalabrutinib with bendamustine and rituximab for previously untreated mantle cell lymphoma. January 16, 2024. Accessed January 16, 2024. https://shorturl.at/fTW0O
2. CALQUENCE® (acalabrutinib) granted priority review in the US for patients with untreated mantle cell lymphoma. News release. AstraZeneca. October 3, 2024. Accessed December 16, 2024. https://tinyurl.com/bdspu2np