
Acalabrutinib, umbralisib, and ublituximab (AU2) treatment is effective in patients with de novo mantle cell lymphoma (MCL), according to a study presented at the 66th American Society of Hematology Annual Meeting & Exposition.
Twelve patients (median age, 70 years) received oral acalabrutinib at 100 mg twice daily, oral umbralisib at 800 mg daily (amended to days 1-14 of cycle 1 and days 1-7 of subsequent cycles), and intravenous ublituximab at 900 mg on days 1, 8, and 15 of cycle 1 and day 1 of subsequent cycles. After cycle 6, patients received maintenance therapy with oral agents and ublituximab every two cycles for 24 cycles. Each cycle was 28 days.
All patients had an Eastern Cooperative Oncology Group performance status of 0-1, six had a TP53 mutation, and one had complex karyotype. For the 11 patients with an available combined Mantle Cell Lymphoma International Prognostic Index score, six (55%) had at least high-intermediate risk. Four of ten patients had a Ki-67 ≥30%.
The researchers used clonoSEQ® assay to assess measurable residual disease (MRD) in the peripheral blood and Fisher’s exact test to assess the relationship between undetectable MRD and subsequent disease progression (PD). Of the 11 patients with available MRD data, eight (73%) achieved undetectable MRD. Of those, three became MRD detectable before experiencing PD. Loss of undetectable MRD, or failure to achieve undetectable MRD, was associated with PD (P=.048) and commonly occurred in patients with TP53 mutation.
Four patients progressed, three remain on therapy, and two died. In the ten surviving patients, the two-year progression-free survival (PFS) was 63%, and the two-year overall survival (OS) was 88. Among patients with TP53 mutation, the two-year PFS and OS were 21% and 67%, respectively.
The most common toxicities of any grade were infusion-related reactions (IRR; 75%), increased aspartate aminotransferase (AST; 67%), diarrhea, and headache (58%). The most common grade ≥3 toxicities were increased AST, increased alanine aminotransferase, and IRRs (all 33%).
Four patients received subsequent therapies after stopping AU2. Two patients achieved response after switching to zanubrutinib, one achieved a CR after chimeric antigen receptor T-cell therapy, and one died after failing multiple lines of therapy.
“AU2 is a highly effective regimen in [patients] with previously untreated MCL, including those with high-risk genetics (100% CR rate), and achieves a high molecular [undetectable] MRD rate. [Patients] who develop progressive disease can be effectively salvaged with subsequent therapies.”
Reference
Lopedote P, Shouse G, Muir A, et al. “Acalabrutinib, umbralisib and ublituximab regimen (AU2) demonstrates high response rate and undetectable molecular minimal residual disease (MRD) in patients (pts) with de novo mantle cell lymphoma (MCL)” Abstract #1633. Presented at the 66th American Society of Hematology Annual Meeting & Exposition; December 7-10, 2024; San Diego, California.