Research regarding treatment for marginal zone lymphoma (MZL), large B-cell lymphoma (LBCL), and mantle cell lymphoma (MCL) presented at the 2023 Tandem Transplantation and Cellular Therapy Meetings of ASTCT and CIBMTR showed promising results with clinical implications.
Results from the phase 2 MAGNOLIA trial (ClinicalTrials.gov Identifier: NCT03846427) confirmed that zanubrutinib induces durable disease control and is well tolerated.1
An interim analysis from the randomized, phase 3 TRANSFORM trial (ClinicalTrials.gov Identifier: NCT03575351) demonstrated the continued clinical benefit of the chimeric antigen receptor T-cell (CAR-T) therapy lisocabtagene maraleucel (liso-cel) compared with standard of care as a second-line treatment for patients with LBCL.2
In addition, results from a phase 1/2 study of CAR-T therapy (ClinicalTrials.gov Identifier: NCT04186520) revealed that LV20.19, a bispecific anti-CD19/CD20 CAR-T construct, expanded with IL7/IL15 is safe and effective for patients with relapsed/refractory (R/R) MCL.3
Zanubrutinib Shows High Response Rates in MZL
Long-term results from the phase 2, multicenter, open-label, single-arm MAGNOLIA study revealed that zanubrutinib induced durable disease control in patients with all subtypes of MZL, including patient groups that are difficult to treat.1
Zanubrutinib, a highly specific next-generation BTK inhibitor, was recently approved for the treatment of patients with R/R MZL based on the primary analysis of the MAGNOLIA trial. The primary endpoint of the study was overall response rate (ORR) by independent review committee (IRC) according to Lugano classification. Secondary endpoints included duration of response, progression-free survival (PFS), overall survival (OS), and safety.
A total of 68 patients with MZL were included in the study (median age, 70 years [range, 37-95 years]; 53% male). Disease subtypes included patients with extranodal (38%), nodal (38%), splenic (18%), and unknown disease (6%). At the time of data cutoff, 34 patients were still receiving zanubrutinib, with the most common reason for treatment discontinuation being progressive disease.
At a median follow-up of 28 months, the ORR by IRC was 68%, with the ORR by investigator assessment being 76%. By IRC, 26% of patients experienced a complete response (CR) with 29% experiencing CR by investigator assessment. The median time to response was approximately 3 months.
All key patient subgroups had a response as evaluated by IRC. There was a high ORR observed across all subtypes of MZL, with the highest seen in patients with nodal disease (76%) and the highest CR rate seen in patients with extranodal disease (40%). PFS was 71%, duration of response was 73%, and the OS rate was 86%, all by IRC.
In terms of safety, all patients experienced at least 1 treatment-emergent adverse event (TEAE), with 48% of patients experiencing a TEAE of grade 3 or higher, including COVID-19 pneumonia (5.9%) and neutropenia (8.8%). The most common TEAEs were bruising (23.5%), diarrhea (22.1%), and constipation (17.6%). However, cardiac TEAEs were rare, with hypertension occurring in 3 patients and atrial fibrillation and atrial flutter in 1 patient each. These results were consistent with pooled analyses of zanubrutinib and no TEAEs led to withdrawal from the study.
As no new safety signals were observed with responses in all MZL subtypes, the investigators concluded the data support the use of zanubrutinib as a treatment for patients with R/R MZL.