B-Cell Depletion With Obinutuzumab May Prevent GVHD

Obinutuzumab administered after hematopoietic stem cell transplantation (HSCT) resulting in B-cell depletion was associated with lower rates of chronic graft vs host disease (cGVHD), according to the results of a trial presented at the ASH Annual Meeting 2023. 

The trial randomly assigned 178 patients who underwent HSCT with peripheral stem cells only to receive obinutuzumab 3 months post-transplant. All patients received tacrolimus-based GVHD prophylaxis, but not post-transplant cyclophosphamide or antithymocyte globulin prophylaxis. 

The primary endpoint was cumulative incidence of steroid-requiring cGVHD. Secondary endpoints included moderate to severe cGVHD, all cGVHD, non-relapse mortality, relapse, progression-free survival, and overall survival.

At baseline, the median age was 57, and 63% of patients were male. The most common hematologic malignancies were acute myeloid leukemia and myelodysplastic syndrome. Approximately two-third of patients received RIC/NMA conditioning and the remaining received MAC. Most patients had donor types of 8/8 unrelated or 8/8 related. Prior grade II-IV acute GVHD occurred among 8% of patients.

The cumulative incidence of steroid-requiring cGVHD was significantly lower with obinutuzumab, with rates of 12% at 1 year and 30% at 2 years compared with 37% and 43%, respectively, with placebo (P =.029). A multivariate analysis demonstrated a 44% decrease in cGVHD requiring steroid treatment in the obinutuzumab group (hazard ratio, 0.56; 95% CI, 0.33-0.94; P =.028).

The rates of moderate to severe cGVHD were lower with obinutuzumab, with rates of 20% and 27% at 1- and 2-years, respectively, compared with 35% and 39%, respectively, with placebo; however, this did not reach statistical significance (P =.056). The rates of all cGVHD were similar between the treatment groups at both 1- and 2-years.

“While all incidents of cGVHD was actually unchanged, and we believe this was due to the diagnosis of mild ocular and oral disease with a thorough analysis currently ongoing,” Corey Cutler, MD, MPH, of the Dana-Farber Cancer Institute in Boston, MA, said when presenting the study.

There was no significant difference in cancer relapse (P =.24) and survival outcomes, including non-relapse mortality (P =.22), PFS (P =.9), and OS (P =.63) with obinutuzumab or placebo.

Grade 3-4 neutropenia was significantly more common with obinutuzumab compared with placebo (P <.001). However, treatment discontinuations due to toxicity were uncommon.

Immune reconstitution was also evaluated, which demonstrated that a subset of patients experienced B-cell reconstitution during year 2 of obinutuzumab treatment. 

Analysis of H-Y minor histocompatibility antibody (HY-Abs) responses among male HSCT recipients demonstrated that pre-existing antibodies were associated with the development of cGVHD regardless of obinutuzumab treatment. However, patients with no pre-existing HY-Abs treated with obinutuzumab did not develop cGVHD, whereas those who received placebo did.

“Prophylactic B-cell depletion after peripheral blood stem cell transplantation is associated with a reduced incident of steroid-requiring cGVHD,” Dr Cutler concluded. “We know for this strategy to be effective, B-cell depletion needs to occur before maturation of B-cells to allo-antibody formation stage.”

Disclosures: Some of the study authors declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of disclosures.

Reference

Cutler C, Kim HT, El Banna H, et al. Effective prevention of steroid-requiring chronic graft-vs.-host disease with B cell depletion: a randomized, placebo-controlled trial. Presented at ASH Annual Meeting 2023. December 9-12, 2023. San Diego, CA. Abstract 649.

This article originally appeared on Hematology Advisor