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Glofitamab Plus Polatuzumab Vedotin Demonstrates Durable Responses Among Pretreated Patients With DLBCL, Including HGBCL
Updated Phase 1b/2 Trial Results With Longer Follow-Up
Updated Phase 1b/2 Trial Results With Longer Follow-Up
According to updated, longer-term follow-up results from a phase 1b/2 study, glofitamab, a CD20-CD3 bispecific antibody, plus polatuzumab vedotin, a CD79b-targeted antibody-drug conjugate, demonstrated high response rates and durable responses among heavily pre-treated patients with diffuse large B-cell lymphoma (DLBCL), including those with high-grade B-cell lymphoma (HGBCL), and with prior chimeric antigen receptor (CAR) T-cell therapy.
Martin Hutchings, MD, PhD, Rigshospitalet, Copenhagen, Denmark, presented data from the trial at the 2023 American Society of Hematology (ASH) Annual Meeting and Exposition in San Diego, California.
At the data cut-off of January 25, 2023, 111 patients had received ≥1 dose of study drug (safety population). Most patients were refractory to their last prior therapy (71.2%). The median number of prior lines of therapy was 2 (range 1 to 7; 61.3% of patients had received ≥2), and 24.3% had received prior CAR T-cell therapy. Investigators noted the primary objective was to establish the recommended phase 2 dose of glofitamab when combined with polatuzumab vedotin.
Eligible patients received obinutuzumab 1000mg on day 1 of the first cycle to mitigate the risk of severe cytokine release syndrome (CRS.) Polatuzumab vedotin was administered on cycle 1 day 2, and day 1 of cycles 2 to 6. The cycles were 21 days. Glofitamab was given with step-up dosing in cycle 1, for up to 12 cycles.
The overall response rate (ORR) in 109 efficacy-evaluable patients was 78%, with a complete metabolic response (CMR) rate of 56%. Among patients with DLBCL not otherwise specified (NOS), the ORR and CMR rates were 85.7% and 60.7%, respectively. Patients with transformed follicular lymphoma (trFL), the ORR and CMR rates were 76.9% and 53.8%, respectively; Patients with high-grade B-cell lymphoma (HGBCL), the ORR and CMR rate were 60.0% and 44.0%, respectively. Additionally, the 2 patients with primary mediastinal large B-cell lymphoma (PMBCL) achieved a CMR.
Among patients who had prior CAR T-cell therapy, the ORR was 77.8% and the CMR rate was 44.4%. Among the 61 patients who had a complete response (CR), the estimated 6- and 12-month duration of complete response (DOCR) rates were 89.2% and 73.1%, respectively. Furthermore, estimated 6-month and 12-month DOCR rates among patients with DLBCL NOS were 84.2% and 59.2%, respectively; with trFL, results were 92.9% and 85.7%; with HGBCL, both were 100%. Among patients with PMBCL, the estimated 6-month DOCR was 100%. With a median follow-up of 13 months, median progression-free survival was 10.4 (95% confidence interval [CI]: 5.8–19) months. The median overall survival was not reached after a median survival follow-up of 15.2 months.
In terms of safety, the most common adverse event among 108 of the 111 patients who had received ≥1 dose of glofitamab was cytokine release syndrome (CRS). Of the 111 safety-evaluable patients, 27 had peripheral neuropathy (all grade 1 or 2, 8 events were resolved). It was noted that glofitamab-related adverse events were potentially consistent with immune effector cell-associated neurotoxicity syndrome (ICANS), which occurred in 3 patients and were all grade 1 or 2. Grade 3 or 4 adverse events were reported in 61.3% of patients, with neutropenia being the most common event. Serious adverse events occurred in 58.6% of patients, and Grade 5 adverse events occurred in 6.3% of patients (5/7 events due to COVID-19); 9.9% of patients discontinued any treatment due to an adverse event.
Dr Hutchings and colleagues concluded that glofitamab plus polatuzumab vedotin treatment “demonstrated high response rates and durable responses in heavily pre-treated patients, the majority of whom were refractory to their last prior therapy, across all histologies, including in patients with HGBCL and those with prior CAR T-cell therapy.”
“The safety profile was manageable and consistent with the individual drugs,” they added.
Source:
Hutchings M, Avigdor A, Sureda Balari AM, et al. Glofitamab plus polatuzumab vedotin continues to demonstrate frequent and durable responses and has a manageable safety profile in patients with ≥2L relapsed/refractory DLBCL, including HGBCL, and in patients with prior CAR T-cell therapy: Updated results from a phase Ib/II study. Presented at ASH Annual Meeting and Exposition; December 9-12, 2023; San Diego, CA. Abstract 4460
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