Blinatumomab appears safe, effective for heavily pretreated DLBCL

Blinatumomab monotherapy appeared effective for the treatment of heavily pretreated relapsed and refractory diffuse large B-cell lymphoma, according to the results of a phase 2 study.

“Since the introduction of the monoclonal anti-CD20 antibody rituximab [Rituxan; Genentech, Biogen Idec], fewer patients with diffuse large B-cell lymphoma [DLBCL] relapse, yet it is now more challenging to find effective salvage chemotherapy regimens for patients with relapsed or refractory DLBCL and prior exposure to rituximab,” Andreas Viardot, MD, PhD, professor of internal medicine at University Hospital of Ulm in Germany, and colleagues wrote.

Thus, Viardot and colleagues sought to observe the efficacy of blinatumomab (Blincyto, Amgen) — a bispecific T-cell engaging antibody construct that transiently links CD3-positive T cells to CD19-positive B cells — in this patient population.

The researchers conducted a phase 2 study evaluating blinatumomab by continuous infusion, with dexamethasone prophylaxis.

The researchers assigned 25 patients (median age, 66 years; range, 34-85; median prior therapy lines, 3) to a stepwise (9 g per day during week 1; 28 g per day during week 2; 112 g thereafter; n = 23) or flat (112 g daily; n = 2) dosing schedule.

Overall response rate (ORR) among evaluable patients — defined as a patient who received the target dose for at least 7 days or who discontinued treatment due to progressive disease — served as the primary endpoint.

The researchers reported that 17 patients ended treatment during the induction cycle, with seven patients discontinuing during the consolidation cycle and one patient discontinuing during retreatment.

Reasons for discontinuing therapy after the induction cycle included disease progression (36%), adverse events (20%) and physician decision (12%).

The analysis included data from 21 evaluable patients, 43% of whom achieved a response after one cycle of blinatumomab. Nineteen percent of patients achieved a complete response.

The researchers further observed a late complete response in three additional patients.

After a median follow-up of 15 months, median PFS was 3.7 months (95% CI, 1.4-7.7). One patient had an ongoing PFS of 20.1 months at time of reporting.

For the entire patient cohort, median OS was 5 months (95% CI, 2.3-not estimable).

Frequently-reported adverse events among patients assigned stepwise dosing included tremor (48%), pyrexia (44%), fatigue (26%) and edema (26%). Grade 3 neurologic events among these patients included encephalopathy (9%), aphasia (9%), tremor (4%), speech disorder (4%), dizziness (4%), somnolence (4%) and disorientation (4%).

Five patients discontinued stepwise dosing due to adverse events. Four patients experienced neurologic adverse events; however, the majority of neurologic events resolved.

The researchers terminated the flat dosing cohort due to neurologic adverse events in both patients.

“Blinatumomab monotherapy may be an effective component of treatment in patients with relapsed or refractory DLBCL, which is a patient population with a high unmet medical need,” Viardot and colleagues wrote. “Stepwise dose escalation to the target dose is needed to mitigate known adverse events, including neurologic events. Because relapsed and refractory DLBCL progresses rapidly, an approach to blinatumomab administration that will allow patients to achieve the target dose without early dropout must be defined in further studies.” – by Cameron Kelsall

Disclosure: Amgen funded this study. Viardot reports research funding, travel expenses and honoraria from, as well as advisory board positions with, Amgen and numerous other pharmaceutical companies. Please see the full study for a list of all other researchers’ relevant financial disclosures.