Highlights from

ASH 2019

61st Annual Meeting & Exposition of the American Society of Hematology

Orlando, Florida (USA) 7 - 10 December 2019

Mosunetuzumab: complete remissions in non-Hodgkin lymphoma

The bispecific anti-CD3 and anti-CD20 monoclonal antibody mosunetuzumab provided durable responses in patients with B-cell non-Hodgkin lymphoma, even in relapsed patients or patients whose disease was refractory to chimaeric antigen receptor (CAR) T-cell therapy.

The dose-escalation trial, presented by Prof. Stephen J. Schuster (University of Pennsylvania, USA), enrolled patients with B-cell non-Hodgkin lymphoma who had received at least 1 prior therapy, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and for whom there was “no available therapy that would be expected to improve survival” [1].

A total of 270 patients (median age 62 years) were enrolled; 164 of those (61.2%) had an ECOG performance status of 1, and 180 (66.7%) were categorised as having aggressive non-Hodgkin lymphoma. The most common diagnosis was diffuse large B-cell lymphoma (DLBCL; n=117, 43.3%), followed by transformed follicular lymphoma (FL; n=32, 11.9%). Participants had received a median of 3 prior systemic therapies (range 1-14). The 30 patients who had had prior CAR T-cell therapy were particularly heavily pre-treated, with a median of 5 prior lines of therapy (range 3-14).

Mosunetuzumab was administered with step-up dosing on days 1, 8, and 15 of cycle 1, followed by fixed doses on day 1 of each 21-day cycle for up to 17 cycles. Patients who achieved a complete remission after the first 8 cycles stopped therapy, while those with a partial response or stable disease continued treatment for the full 17 cycles.

In the group of 124 patients with aggressive non-Hodgkin lymphoma who received mosunetuzumab in doses ranging from 2.8 mg to 40.5 mg, the objective response rate (ORR) was 37.1%, with a complete remission rate of 19.4%. Complete remissions appeared to be durable, with 17 of 24 patients remaining in complete remission for up to 16 months after stopping treatment. Similar response rates and durability were seen in the group with indolent non-Hodgkin lymphomas (who received mosunetuzumab at doses ranging from 2.8 mg to 13.5 mg): ORR was 62.7% and complete remission rate was 43.3%. Even in the subgroup of those who had previously received CAR T-cell therapy, the ORR was 39% and the complete remission rate was 22%.

The adverse events seen with mosunetuzumab were mostly low grade and similar to those typically observed with CAR T-cell therapies; cytokine release syndrome occurred in 28.9% of patients, which were almost all grade 1 or 2 in severity (96.2%). Neurologic toxicity occurred in 43.7% of patients, including headache (15.6%), insomnia (9.3%), and dizziness (9.3%).

Keywords: mosunetuzumab; Non-Hodgkin Lymphoma; B-Cell Lymphoma; Adoptive Immunotherapy; Chimaeric Antigen Receptors; Follicular Lymphoma

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The content and interpretation of these conference highlights are the views and comments of the speakers/authors.