According to the results of a single-arm phase 2 trial published in Blood Advances, ofatumumab in combination with prednisone demonstrated acceptable safety and potential efficacy as initial therapy in chronic graft vs host disease (cGVHD).
The investigators previously established the safety and feasibility of therapy with ofatumumab (1000 mg IV on days 0 and 14) and prednisone (1 mg/kg/day) in adult patients with cGVHD requiring systemic glucocorticoid therapy in the phase 1 portion of the trial (n = 12; ClinicalTrials.gov Identifier: NCT01680965). The new publication presented the mature results of the phase 2 expansion of the trial (n = 38) examining the safety and efficacy of the combination for initial therapy of cGVHD.
The investigators noted that the development and launch of the trial predated currently accepted National Institutes of Health (NIH) response metrics. The primary efficacy endpoint was the 6-month clinician-reported overall response rate (ORR; composite of complete response [CR] and partial response [PR]). The 6-month ORR per 2014 NIH response criteria was also reported.
Patients had a median age of 59.5 years (range, 26-84), and 65.8% of the patients were male. The most common allogeneic hematopoietic cell transplantation indications were acute leukemia (36.8%), myelodysplastic syndrome (23.7%), and non-Hodgkin lymphoma (13.2%). Most patients had received peripheral blood stem cell transplants (92.1%) from unrelated donors (matched, 63.2%; unmatched, 7.9%). The overall NIH severity of cGVHD was moderate and severe in 63% and 37% of patients, respectively. Most patients were affected by the overlap subtype of cGVHD (74%) and by prior acute cGVHD (82%).
The investigators found that the 6-month clinician-reported ORR (62.5%; CR = 15.6%; PR = 46.9%) and the 2014 NIH-defined ORR (62.5%; CR = 9.4%; PR = 53.1%) were not superior to a prespecified historic benchmark of 60%.
They found a suggested benefit of the ofatumumab combination when comparing the 6-month NIH-defined ORR of 62.5% with more contemporaneous benchmark ORR of 48.6% with frontline sirolimus/prednisone (CTN 0801 trial; lower confidence interval [CI] limit, 51.5%; P =.056).
The researchers also reported a failure-free survival (FFS) of 64.2% (95% CI, 46.5-77.4%) at 6 months and 53.1% (95% CI, 35.8-67.7%) at 12 months. Post-hoc analysis demonstrated that FFS with CR/PR at 12 months (33.5%) exceeded a benchmark of 15% and had a higher likelihood of complete steroid discontinuation by 24 months (odds ratio, 8; 95% CI, 1.21-52.7).
“In summary, our single-arm phase 2 trial demonstrated acceptable safety and efficacy for key NIH-defined treatment outcomes after upfront use of ofatumumab in cGVHD,” concluded the investigators. “Future strategies may employ B-cell targeting agents in novel trial designs alone, with low-dose prednisone, or in combination with other targeted therapies.”
Limitations of the study included variation in the cGVHD features of enrolled patients, aggressive prednisone-tapering practices on trial, interrater variability in physician response assessment, and a modest sample size.
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Lazaryan A, Lee S, Arora M, et al. A phase 2 multicenter trial of ofatumumab and prednisone as initial therapy for chronic graft-versus-host disease. Blood Adv. 2022;6(1):259-269. doi:10.1182/bloodadvances.2021005552