Giving the bispecific antibody glofitamab for a finite duration induces durable complete remissions in heavily pretreated patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), according to results of a study presented at the 2022 ASCO Annual Meeting.
“R/R DLBCL has a particularly poor prognosis, and even more so after 2 prior lines of therapy. [Chimeric antigen receptor] (CAR)-T cell therapy is an option, but it is often an issue in terms of deliverability and availability,” explained presenting author Michael Dickinson, MBBS, DMed Sci, FRACP, FRCPA, from the Peter MacCallum Cancer Centre, Royal Melbourne Hospital, and University of Melbourne in Australia. “Glofitamab is a CD20 [B cell]-, CD3 [T cell]-bispecific antibody which is unique due to the potency derived from its 2-to-1 format. It’s also unique because it’s given in a fixed-course schedule.”
Dr Dickinson presented results from a pivotal phase 2 expansion trial in which 154 patients with R/R DLBCL and other non-Hodgkin lymphomas who had received 2 or more prior lines of therapy were administered glofitamab on 21-day cycles, for up to 12 cycles. The investigators used a step-up dosing regimen with a target dose of 30 mg. The primary outcome was the complete response (CR) rate.
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The patients had a median age of 66.0 years (range, 21-90), and 71.4% had DLBCL. They had received a median of 3 prior lines of therapy (range, 2-7).
Most of the cohort had disease that was refractory to prior anti-CD20 antibody-containing regimens (83.1%), to their most recent therapy (85.7%), and to their initial therapy (58.4%). One-third (33.1%) had disease that was refractory to prior CAR-T therapy.
At a median follow-up of 12.6 months, the overall response rate was 51.6% and the CR rate was 39.4%. Median time to CR was 42 days (95% CI, 42-44).
In a subgroup analysis, CR rate did not differ between patients who did and did not have prior CAR-T therapy exposure (35% vs 42%). The rate was significantly higher among patients whose disease relapsed after last therapy than among those whose disease was refractory to last therapy (70% vs 34%).
The median duration of overall response was 18.4 months, and the median duration of CR was not estimable. Median progression-free survival was 4.9 months and overall survival was 11.5 months.
Cytokine release syndrome occurred in 63.0% of the cohort. Most of these events were grade 1 (fever), seen in 47.4% of patients; few were of grade 2 (11.7%), grade 3 (2.6%), or grade 4 (1.3%).
No glofitamab-related fatal events occurred; overall, 9.1% of patients discontinued treatment due to adverse events.
“We saw complete remissions in 39.4% of patients following treatment with this fixed-course therapy, irrespective of CAR-T exposure, and these data reflect our routine practice and an area of need in this disease. Remissions came on early and importantly, were durable. We have observed very long durations of complete remission when we look across the whole trial,” Dr Dickinson stated.
“I think these results will prove to be very meaningful for our patients with large-cell lymphoma and this drug will prove to be an important treatment option for patients with R/R DLBCL and subtypes,” he concluded.
Disclosure: This research was supported by F. Hoffmann-La Roche Ltd and Genentech Inc. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Reference
Dickinson M, Carlo-Stella C, Morschhauser F, et al. Glofitamab in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) and ≥ 2 prior therapies: Pivotal phase II expansion results. Presented at ASCO 2022; June 3-7, 2022. Abstract 7500.
