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.

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Max S. Topp, MD, discusses the safety profile of glofitamab in combination with R-CHOP in patients with diffuse large B-cell lymphoma. 
 


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

Max S. Topp, MD, head of the Department of Hematology, University Hospital of Würzburg, in Würzburg, Germany, discusses the efficacy of the combination of glofitamab plus R-CHOP (rituximab [Rituxan], cyclophosphamide, doxorubicin, vincristine, and prednisone) from a phase 1 trial (NCT03467373) done in previously untreated patients with diffuse large B-cell lymphoma (DLBCL).

Data from both the safety run-in portion and the expansion stage of the study were presented at the 2022 ASH Annual Meeting. All agents that comprised the R-CHOP regimen were administered at a categorized dose intensity of at least 90% in more than 90% of patients, except for vincristine, which was received at a dose intensity of at least 90% in 62.5% of patients, Topp notes.

Among 56 evaluable patients with DLBCL, the 53 who were exposed to glofitamab comprised the efficacy population, Topp adds. The combination elicited an overall response rate of 86.8% and a complete metabolic response rate of 75.5% in this population, Topp concludes.

Max S. Topp, MD, discusses the efficacy of the combination of glofitamab plus R-CHOP from a phase 1 trial done in previously untreated patients with diffuse large B-cell lymphoma.

Dr Topp on the Efficacy of Glofitamab Plus R-CHOP in Previously Untreated DLBCL

Max S. Topp, MD, professor and head of Haematology, University Hospital of Wuerzburg, Germany, discusses the phase III TOWER study, which looked at blinatumomab (Blincyto) versus standard chemotherapy in patients with Philadelphia chromosome—negative relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL), In the study, median overall survival (OS) with blinatumomab was 7.7 months versus 4 months with standard chemotherapy.

Treatment with blinatumomab reduced the risk of death by 29% versus standard chemotherapy (HR, 0.71; 95% CI, 0.55-0.93; P = .012) and the CR rate with blinatumomab was 39% versus 19% with standard chemotherapy (P <.001).

This trial has established blinatumomab as the therapy of choice for relapsed or refractory ALL, said Topp.

Max S. Topp, MD

Articles

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

Dr Topp on the Efficacy of Glofitamab Plus R-CHOP in Previously Untreated DLBCL

Dr. Max Topp on the TOWER study and Blinatumomab in ALL