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Obinutuzumab plus zanubrutinib, pomalidomide, and venetoclax produced high response rates in high-risk MCL.
Obinutuzumab (Gazyva) in combination with zanubrutinib (Brukinsa), pomalidomide (Pomalyst), and venetoclax (Venclexta) was active in patients with high-risk mantle cell lymphoma (MCL), according to data from a prospective, single-center, clinical study (BYSYJC20240071) presented during the
Patients who received the quadruplet (n = 15) achieved an overall response rate (ORR) of 100% and a complete response (CR) rate of 86.7% at course 6. At a median follow-up of 14 months, the 1-year progression-free survival rate was 93.3% and the 1-year overall survival rate was 100%.
“High-risk MCL lacks effective treatment options and has a poor prognosis, posing challenges in management. The [National Comprehensive Cancer Network] guidelines recommend clinical trials as the first choice [of treatment for these patients],2” Ping Yang, MD, of the Department of Hematology at Peking University Third Hospital in Beijing, China, and colleagues wrote in a poster presentation of the data. “Combination regimens or multiple targeted agents have become a common clinical option, yet no standardized regimen has been established.”
The study enrolled adult patients with a confirmed diagnosis of MCL with adequate organ function. Patients were also required to have high-risk disease and at least 1 of the following risk factors: blastoid variant, TP53 mutation, or TP53 deletion.
All patients received obinutuzumab at 1000 mg on day 1, in combination with zanubrutinib at 160 mg twice daily, pomalidomide at 4 mg on days 1 through 14, and venetoclax at 200 mgon days 1 through 14 for six 28-day cycles. If the regimen was effective, patients then received obinutuzumab at 1000 mg on day 1 every 3 months plus zanubrutinib at 160 mg twice daily for 2 years and pomalidomide at 4 mg and venetoclax at 200 mg on days 1 through 14 of each 28-day cycle for 1 year as maintenance therapy.
The primary end point was ORR per Lugano 2004 criteria. Minimal residual disease (MRD) status was assessed by next-generation sequencing (NGS) in peripheral blood.
At baseline, the median age among all patients enrolled in the study was 61 years (range, 44-78). Most patients were male (80.0%), had high-/high-intermediate–risk disease per combined MCL International Prognostic Index score (80.0%), had blastoid or pleomorphic disease (73.3%), had a Ki67 score of at least 50% (66.7%), had a TP53 mutation or deletion (66.7%), and had a TP53 aberration combined with high-risk gene mutation (53.3%). The study included patients with untreated (n = 12) and relapsed/refractory MCL (n = 3). Patients with relapsed/refractory disease received a median of 1 (range, 1-4) prior lines of therapy.
What were the additional efficacy and safety data?
Additional findings from the study revealed that at the end of course 3, the ORR and CR rate were 100.0% and 80.0%, respectively. Among 12 patients who underwent MRD testing after 6 cycles of therapy, 100% of patients achieved undetectable MRD status per NGS. In terms of safety, the most common grade 3 to 4 adverse effects included neutropenia (60.0%), thrombocytopenia (20.0%), and infections (13.3%).
“Our results provide preliminary evidence that the quaduple drug combination of obinutuzumab, zanubrutinib combined with pomalidomide and venetoclax is an active regimen in high-risk MCL and should be evaluated in a prospective randomized controlled trial,” Yang and colleagues wrote in their conclusion.
