Dr. Topp on the Safety Profile of Glofitamab Plus R-CHOP in DLBCL

Max S. Topp, MD, head,the Department of Hematology, University Hospital of Würzburg, in Würzburg, Germany, discusses the safety profile of glofitamab in combination with R-CHOP (rituximab [Rituxan], cyclophosphamide, doxorubicin, vincristine, and prednisone) in patients with diffuse large B-cell lymphoma (DLBCL).

The safety, activity, pharmacokinetics, and pharmacodynamic effects of the first-line combination regimen of R-CHOP and glofitamab were evaluated in a phase 1 trial (NCT03467373) of previously untreated patients with non-Hodgkin Lymphomas, including DLBCL.

The trial evaluated 56 patients at the time of data cutoff, Topp states. A preliminary analysis of the patient population demonstrated that adverse events (AEs) were experienced by nearly all patients, with 71.4% of patients experiencing severe AEs grade 3 or above. However, 23.2% of the AEs experienced were glofitamab-related.

Common AEs included neutropenia, thrombocytopenia, and infections such as pneumonia, Topp continues. Neurotoxicity was observed in several patients but was not primarily attributed to glofitamab use, he explains. Severe infections were seen in 9 patients, 8 of which were caused by COVID-19.

Additionally, the incidence and severity of cytokine release syndrome (CRS) in all safety evaluable patients was low, with a CRS rate of 10.7% for all grades, Topp notes. This percentage was reduced to 7.1% and 3.6% for grade 1 and 2 events, respectively. CRS occurred in 3 patients following the addition of intravenous glofitamab on day 8 of the second cycle of R-CHOP. Three more patients experienced CRS due to step-up dosing at day 15 of cycle 2, and 1 patient experienced CRS after administration of the target dose in cycle 3.

These findings demonstrate that the addition of glofitamab to first-line R-CHOP is safe and tolerated in this patient population, Topp says. Moreover, the low CRS risk specifically indicated that the combination could be successfully utilized in an outpatient setting, he concludes. Glofitamab was recently granted priority review status by the FDA for relapsed/refractory LBCL.