A Peter Mac-initiated clinical trial suggests a way to dramatically improve outcomes in patients with high-risk forms of large B-cell lymphoma, who otherwise have a 50% chance of cure from conventional therapy.

Patients enrolled in the COALITION trial were all aged 18 to 65 years and showed clinical features, or had a genetic test result, indicating "high risk" their cancer would not respond to, or relapse after, standard therapies.

All patients received one of two standard treatment regimens, either "R-CHOP" or "Pola-R-CHP." This Phase II trial assessed the safety and efficacy of adding the drug glofitamab to each of these regimens.

"This trial involved a group of patients in whom poor outcomes are common with only half expected to be cured by conventional treatments," says Dr. Adrian Minson, a lymphoma specialist at Peter Mac who co-led the national trial together with Professor Michael Dickinson, the Lead of Aggressive Lymphoma.

"However, when glofitamab was added to these commonly used R-CHOP and Pola-R-CHP treatment regimens, we saw potent and durable responses in almost all patients."

Of the 80 patients in the trial, over 95% completed the therapy (either R-CHOP or Pola-R-CHP plus glofitamab). Among these, 98% had a "complete response," meaning their blood cancer became undetectable on the most sensitive of scans.

There were no major new toxicities observed and side effects were considered manageable. At follow-up almost two years later (median follow-up 21 months), progression-free and overall survival rates were 86% and 92% respectively.

Professor Dickinson says, "These results are exciting and support an ongoing larger Phase III clinical trial to assess glofitamab as a first-line treatment, in combination with other therapies, for high-risk forms of large B-cell lymphoma."

These results have just been published in the Journal of Clinical Oncology, in a paper titled "Glofitamab Combined with Pola-R-CHP or R-CHOP as First Therapy in Younger Patients with High-Risk Large B Cell Lymphoma: Results from the COALITION study."

The COALITION trial was investigator-initiated by Professor Dickinson and Dr. Minson, sponsored by Peter Mac, and involved patients at Peter Mac and 14 other Australian sites.

Glofitamab is a type of antibody treatment that helps the immune system attack lymphoma cells, and a benefit of this type of drug is that it can be used alongside, and potentially improve outcomes of, chemotherapy-based treatments.

R-CHOP is a common chemotherapy-based treatment that includes five drugs: rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone. Pola-R-CHP is similar but swaps vincristine for polatuzumab vedotin.