A randomized study of R-miniCHOP with or without oral azacitidine in patients with newly diagnosed diffuse large B cell lymphoma (DLBCL), grade 3B follicular lymphoma (FL), transformed lymphoma, and high-grade B-cell lymphomas with MTC and BCL2 and/or BCL6 rearrangements, was presented at the 2021 American Society of Hematology (ASH) Annual Meeting to evaluate the effects of therapy on quality of life and functional status.

No clear standard of care exists for older patients with DLBCL since this group is often underrepresented in clinical trials, according to Elizabeth A Brem, MD, Division of Hematology/Oncology, Department of Medicine, University of California, Irvine, Orange, and co-investigators. Thus, the dose attenuated version of the standard R-CHOP, known as R-miniCHOP, is often chosen.

Pre-clinical models show that pre-treatment with azacitidine improves the anti-tumor effect of R-CHOP, which is beneficial in older patients since epigenetic deregulation is a feature in this population with DLBCL. Thus, the National Clinical Trials Network developed the S1918 trial.

“This is the first randomized study in this population conducted in North America by the NCTN and will enroll a total of 384 eligible patients after a safety run-in phase. All patients will receive pre-phase therapy with vincristine 1 mg x 1 and prednisone 60mg/m² x 7 days (capped at 100mg/day); pre-phase therapy has been shown to improve performance status and decrease early treatment-related mortality (Owens CN, 2015),” wrote Dr Brem and colleagues.

The S1918 study contains phase 2 and phase 3 components. The primary objective of the phase 2 component is to determine whether the oral azacitidine plus R-miniCHOP regimen should be tested against R-miniCHOP based on the 1-year progression-free survival (PFS). The primary objective of phase 3 is to compare overall survival (OS) at 2 years between oral azacitidine plus R-miniCHOP and R-miniCHOP alone.

“S1918 has the potential to impact future trial design and to change the standard of care for patients 75 years and older with aggressive lymphoma in a number of ways given its randomized design, incorporation of geriatric assessments, and utilization of ctDNA correlatives,” concluded Dr Brem and colleagues.

Elizabeth B, Li H, Beaven AW, et al. S1918: A Phase II/III Randomized Study of R-Minichop with or without Oral Azacitidine (CC-486) in Participants Age 75 Years or Older with Newly Diagnosed Diffuse Large B Cell Lymphoma, Grade IIIb Follicular Lymphoma, Transformed Lymphoma, and High-Grade B-Cell Lymphomas with MYC and BCL2 and/or BCL6 Rearrangements. Presented at: the 2021 ASH Annual Meeting; Dec. 11-14; 2021; Abstract 3565.