CONFERENCE UPDATE: ASH 2023

Mosunetuzumab demonstrates consistent efficacy in patients with R/R follicular lymphoma after ≥2 prior treatments: 3-year follow-up from a pivotal phase 2 study

HEMATOLOGY
23 Jan 2024

STUDY DESIGN

Mosunetuzumab is a T-cell-engaging bispecific antibody that redirects T cells to eliminate malignant B cells.1 It has been approved for the treatment of relapsed and/or refractory (R/R) follicular lymphoma (FL) after ≥2 prior systemic treatments.1 Previous analysis of the pivotal phase II study at a median follow-up of 18.3 months has shown mosunetuzumab’s high response rates with durable responses in heavily pre-treated patients with R/R FL.1 A subsequent analysis with a median follow-up of 37.4 months was conducted to provide updated results from the study.1

The pivotal phase II study was a single-arm study that investigated the efficacy and safety of mosunetuzumab among R/R FL patients pre-treated with ≥2 prior treatments.1 90 patients with R/R FL and ≥2 prior therapies, including an anti-CD20 antibody and an alkylator, were enrolled and were administered mosunetuzumab intravenously in 21-day cycles.1 Dosing was stepped up from 1mg to 60mg in cycle 1.1 All patients received 8 cycles of treatment, with those who showed partial response (PR) or stable disease (SD) continuing treatment until cycle 17.1 Retreatment was permitted at relapse for patients who achieved complete response (CR).1

The endpoints assessed in this update analysis included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.1

Efficacy:

  • The efficacy endpoints of this updated analysis included DOR, PFS, and OS1
  • The median DOR was 35.9 months (95% CI: 20.7-NE)1
  • The 30-month DOR rate was 56.6% (95 CI: 44.2-68.9)1
  • The median DOR in patients who achieved CR (n=54) was 35.9 months (95% CI: NE-NE) while the median DOR in those who achieved PR (n=16) was 4.0 months (95% CI: 2.5-6.7)1
  • 72.7% (95% CI: 60.8-86.8) of patients who achieved CR were estimated to remain alive and progression-free for 30 months after their first response1
  • At the median follow-up of approximately 36 months, the median PFS of the study population was 24.0 months (95% CI: 12.0-NE), with 43.2% of patients remaining progression-free1
  • The median OS of the study population was not reached, with 82.4% of patients remaining alive for 36 months after treatment initiation1

Safety:

  • Overall, the safety profile of mosunetuzumab was manageable among the study population, with no new adverse events (AEs) being reported since the previous data cut-off1
  • The incidence of AEs and serious AEs remains unchanged in this extended follow-up1
  • 51% and 33% of patients experienced mosunetuzumab-related grade 3/4 AEs and mosunetuzumab-related serious AEs, respecitvely1
  • An overall 4% of patients discontinued treatment due to AEs, with 2% of patients discontinuing their treatment due to mosunetuzumab-related AEs1
  • The incidence of cytokine release syndrome (CRS) events was 44%, which were predominantly low grade (grade 1: 26%; grade 2: 17%) and occurred in cycle 1. All CRS events were eventually resolved. No new events were reported in this extended follow-up1
  • Peripheral blood B-cell depletion occurred in all patients (n=74) by the initiation of cycle 2. Median recovery to quantitative levels and normal levels were 18.4 months and 25.1 months, respectively

 

“In heavily pre-treated patients with R/R FL, fixed-duration mosunetuzumab is well-tolerated and can achieve long-lasting remissions.”
Dr. Stephen Schuster
Lymphoma Program,
Abramson Cancer Center,
University of Pennsylvania,
Philadelphia, PA

 

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Pivotal results of phase 1/2 study: Novel mosunetuzumab elicits clinically durable response and deep remission in rrFL patients who underwent ≥2 prior lines of therapy

Follicular lymphoma (FL) is characterized by periodic relapses, refractoriness, reduced progressionfree survival (PFS), and a low response rate with successive conventional treatment lines. Progression of FL within 24 months from the initial start of therapy (POD24) and its refractory nature result in poor prognosis.1 Hence, a potent alternative treatment is essential, given the refractory and unyielding nature of FL.

This phase 1/2 study of 90 pretreated patients evaluated the effectiveness of mosunetuzumab, which is a CD20 x CD3 bispecific antibody (Ab) that redirects T cells to destroy malignant B cells.1 Patients with relapsed/refractory (rr) FL who received at least ≥2 prior lines of therapy (3L + rrFL) were administered with mosunetuzumab monotherapy1. The selection criteria for the cohort of patients were grade 1-3a FL, the Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤1 and at least ≥2 prior lines of therapy.1 Mosunetuzumab was infused by step-up dosing in cycle 1 (C1) to mitigate the effects of cytokine release syndrome (CRS), facilitating treatment without hospitalization.1 Results after the median follow-up of 18.3 months revealed that mosunetuzumab fixed-term treatment (21 cycles) was durable and increased complete response (CR) rates in FL patients.1 The study met the primary endpoint with a significantly high CR rate.1 As per the findings of the study, mosunetuzumab, which can also be administered as an off-the-shelf outpatient therapy, elicited a durable efficacy, a high CR rate and a tolerable safety profile.1
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