Glofitamab Shows Staying Power When Paired With R-CHOP or Pola-R-CHP in LBCL

Glofitamab produced high rates of durable responses when combined with R-CHOP or Pola-R-CHP in younger patients with high-burden, high-risk (HR) large B-cell lymphoma (LBCL), according to results from the phase II COALITION study.

The phase II, open-label, multicenter study was conducted at over 15 centers across Australia and led by Adrian Minson, MBBS, PhD, of the Peter McCallum Cancer Center. It was published in the Journal of Clinical Oncology.

The trial included patients 18-65 with HR LBCL who were either untreated or received one cycle of R-CHOP. Patients with IPI greater than or equal to three, NCCN-IPI greater than or equal to four, or the presence of double-hit (DH) lymphoma characterized by MYC and BCL2 and/or BCL6 rearrangements using fluorescent in situ hybridization (FISH) were classified as high risk. Patients with transformed indolent lymphoma

(tiNHL), excluding Richter’s syndrome, were eligible if they had not received a regimen including anthracycline. The study excluded patients with CNS involvement by lymphoma.

The primary objective of the study was the safety of the treatment, along with the deliverability of the protocol treatments. Secondary end points included objective (ORR) and complete response (CR) rates, progression-free survival (PFS), and overall survival (OS).

Of the 81 patients recruited to the study from July 2021 to July 2023, 80 were deemed eligible to participate. The data cutoff date was August 15, 2024.  After one cycle of R-CHOP, patients were put into arm A or arm B. Patients in arm A received an additional five 21-day cycles of R-CHOP with glofitamab. Patients in arm B received Pola-R-CHP and glofitamab on the same schedule. Each arm received two cycles of glofitamab monotherapy at the conclusion of combination therapy. The median age of the study was 58 (24-65), 51 were male, and 29 were female.

The ORR was 100, and the complete metabolic response was 98%. The 12-month PFS was 92% overall, 90% in arm A and 95% in arm B. The 12-month OS was 97% overall and 98% in both arms. The 24-month PFS was 86% across the board. The 24-month OS was 92% overall in arm A and 91% in arm B.

Ninety-nine percent of patients experienced at least one adverse effect (AE). Peripheral neuropathy was the most observed AE, occurring in 44% of the study population overall. Febrile neutropenia occurred in 15% of arm B. Grade 3 or higher was observed in 58% of patients. One grade 5 AE was observed in each arm.

“This is a very strong endorsement of the ongoing randomized clinical trial of R-CHP with glofitamab versus R-CHP (SKYGLO) that is currently running globally and continues to recruit in multiple centers across the US. It suggests the potential of this regimen to have positive outcomes in that clinical trial,” study author Michael J. Dickinson, MBBS, DMSc of Peter MacCallum Cancer Center, told Blood Cancers Today.