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Although the survival outcomes for patients with follicular lymphoma (FL) have advanced, there is an unmet need for improved tumor control and extended progression-free survival (PFS) in this population, due to variability FL management.
During the 17th International Conference on Malignant Lymphoma (17-ICML), updates from five key trials of novel therapies for the treatment of relapsed/refractory (R/R) FL were presented. Here, we are pleased to summarize these updates; Zinzani presented an updated analysis on the efficacy of zanubrutinib plus obinutuzumab,1 Novelli presented the efficacy and safety of odronextamab,2 Sehn presented an updated analysis of a phase II study of mosunetuzumab,3 Belada presented pooled analyses from the ongoing EPCORE NHL-2 trial,4 and Morschhauser presented data from the TRANSCEND study.5
ROSEWOOD (NCT03332017) is an open-label, randomized, global phase II trial investigating zanubrutinib plus obinutuzumab versus obinutuzumab monotherapy in patients aged ≥18 years with R/R FL who had received ≥2 prior lines of therapy. The primary endpoint was overall response rate (ORR) assessed by an independent review committee (IRC) according to Lugano 2014 criteria. Key secondary endpoints included duration of response (DoR), PFS, overall survival (OS), time to next treatment, and safety.
Figure 1. Grade ≥3 non-hematologic TEAEs*
TEAE, treatment-emergent adverse event; IRR, infusion-related reaction.
*Adapted from Zinzani.1
This follow-up analysis demonstrated the efficacy and manageable safety profile of zanubrutinib plus obinutuzumab in heavily pretreated patients with R/R FL, potentially representing a novel combination therapy for this patient population. The phase III MAHOGANY study (NCT05100862) is currently investigating this combination in patients who have received ≥1 lines of systemic therapy.
ELM-2 (NCT03888105) is an open-label multicenter, multi-cohort, phase II study investigating odronextamab monotherapy with step-up dosing in Cycle 1. The FL cohort for this analysis comprised patients with R/R FL Grade 1–3a who were heavily pretreated (≥2 prior lines of therapy). The primary endpoint was ORR assessed by IRC. Key secondary endpoints included PFS, OS, and safety.
The FL cohort analysis demonstrates the efficacy of odronextamab, with deep and durable responses. The optimized step-up regimen of odronextamab was well-tolerated, highlighting the potential of odronextamab for the treatment of heavily pretreated patients with R/R FL. Future phase III randomized controlled studies are warranted to establish these findings.
This multicenter phase II trial (NCT02500407) evaluated the safety and efficacy of mosunetuzumab monotherapy, with step-up dosing in Cycle 1, in heavily pretreated patients (≥2 lines of prior therapy) with R/R FL. The primary endpoint was CRR determined by IRC and key secondary endpoints included PFS and OS.
Fixed-duration mosunetuzumab demonstrated a high CRR at end of treatment in heavily pretreated patients with R/R FL. Responses were sustained, with a high proportion of patients remaining progression free at 2 years. CRS events were low grade and occurred more often in patients with bone marrow metabolic disease burden.
EPCORE NHL-2 (NCT04663347) is an ongoing phase Ib/II open-label trial. This pooled analysis comprised treatment arms 2a and 2b, including patients with R/R FL who received subcutaneous epcoritamab (48 mg), with step-up dosing, and rituximab (375 mg/m2) plus lenalidomide (20 mg daily) for 12 cycles. The primary endpoints were safety and antitumor activity.
Epcoritamab with rituximab plus lenalidomide demonstrated high overall responses and CMRs, regardless of POD24 status. The safety profile was manageable and consistent with previous reports. Other ongoing trials such as EPCORE FL-1 (NCT05409066) are further evaluating epcoritamab subcutaneous combination regimens.
TRANSCEND (NCT04245839) is an open-label, multicenter phase II trial. This primary analysis is focused on assessing the efficacy of lisocabtagene maraleucel (liso-cel) in patients with R/R FL who had received ≥2 prior therapies (3L + FL cohort) and safety across the whole R/R FL cohort (2L + FL). The primary endpoint was ORR determined by IRC, using Lugano 2014 criteria, and key secondary endpoints were CRR, DoR, PFS, and safety.
Liso-cel achieved deep and durable remissions in patients with R/R FL after three lines of therapy and had a manageable safety profile, with no new safety signals identified. These findings suggest liso-cel as a potential new treatment option for patients with R/R FL.
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