Highlights in follicular lymphoma

In this daily highlights video from ASH 2024, Dr Erika Haydu, heamatologist at the Massachusetts General Hospital in Boston, shares the key take home messages from an oral abstract session discussing new treatment options for patients with follicular lymphoma (FL).

In the frontline setting, interesting data were presented for the phase 2 Mithic-FL1 study. This trial evaluates the anti-CD20, anti-CD3 bispecific T-cell engager (BITE) mosunetuzumab as monotherapy in the treatment of newly diagnosed FL patients with a high disease burden. The primary results of this trial revealed an overall response rate (ORR) of 96%, with 80% of patients obtaining a complete response (CR). Interestingly, 86% of patients in the study experienced a tumor burden reduction of at least an 80% reduction. The 1-year progression-free (PFS) and overall survival (OS) rates were reported at 91% and 99%, respectively. Importantly, the responses induced by mosunetuzumab proved to be very durable with an estimated 90% of patients with a CR maintaining this response for at least 1 year.¹ As such, the results obtained with this chemotherapy-free regimen are very similar to what is observed with classical chemo-immunotherapy and certainly warrant further evaluation of this agent in this setting.

In the relapsed/refractory (R/R) setting, results of the phase 1/2 Epcore NHL-2 trial were presented. This study evaluates the combination of the anti-CD20, anti-CD3 bispecific antibody epcoritamab with lenalidomide-rituximab (R²) in 111 patients with R/R FL. Overall 59% of the patients enrolled in this study had a FLIPI index of 3-5, 50% progressed within 24 months (POD24) and 55% was primary refractory. Just over half of the patients (57%) received the epcoritamab-R² combination in 2^nd line. The ORR obtained with this regimen was reported at 96%, including a CR in 87% of patients. Responses were very durable, with a 21-month duration of response rate of 78%, increasing to 86% among patients with a CR. At 21 months, 80% of patients were progression-free.²

Another exciting novel treatment option for patients with R/R FL consists of the combination of loncastuximab tesirine, a CD19 directed antibody-drug conjugate (ADC), with rituximab. ASH featured the presentation of the primary results of a single-institution phase II trial evaluating this regimen in 39 R/R FL patients. After 12 weeks of therapy, the ORR in this study reached 97.4% with 66.7% of patients having a CR. The 1-year PFS and OS rates reached 94.6% and 94.1%, respectively.³

A final abstract that was selected by Dr Haydu described the safety and efficacy of AZD0486, a novel CD19xCD3 T-cell engager, in a cohort of heavily pretreated R/R FL patients. Two thirds of patients in this study had received ≥3 prior lines of therapy, with 15% of patients being pre-treated with an anti-CD19 CAR-T construct and 10% being exposed to an anti-CD20 bispecific antibody. Despite the heavily pretreated nature of the study cohort, AZD0486 induced an ORR of 95%, with a CR rate of 85%. Importantly, these high response rates were also seen in patients with POD24 (ORR and CR rate 100%), bulky disease (ORR: 78%, CR: 56%), CD20-negative disease (ORR: 100%, CR: 83%) or refractory disease (ORR and CR: 83%). Among patients who previously received an anti-CD20 T-cell engager the CR rate was reported at 75%, while this rate reached 67% among CAR-T pretreated patients. One year after the start of therapy, 75% of patients were alive and free of progression.

As such, the list of promising new treatment options for patients with FL continues to grow. However, with this increasing number of options also comes to challenge to determine the optimal treatment sequence. For Dr Haydu, answering this question will be one of the more important research endeavors for the years to come.