FDA Approval Summary: Ruxolitinib for Treatment of Chronic Graft-Versus-Host Disease after Failure of One or Two Lines of Systemic Therapy.

On September 22, 2021, the Food and Drug Administration approved ruxolitinib for the treatment of chronic graft-versus-host disease (cGVHD) after the failure of one or two lines of systemic therapy in adult and pediatric patients 12 years and older. Approval was based on Study INCB 18424-365 (REACH-3; CINC424D2301; NCT03112603), a randomized, open-label, multicenter trial of ruxolitinib in comparison to best available therapy (BAT) for the treatment of corticosteroid-refractory cGVHD occurring after the allogeneic hematopoietic stem cell transplantation. A total of 329 patients were randomized 1:1 to receive either ruxolitinib 10 mg twice daily (n = 165) or BAT (n = 164). BAT was selected by the investigator prior to randomization. The overall response rate through Cycle 7 Day 1 was 70% (95% CI, 63-77) in the ruxolitinib arm, and 57% (95% CI, 49-65) in the BAT arm. The median duration of response, calculated from first response to progression, death, or initiation of new systemic therapies for cGVHD, was 4.2 months (95% CI, 3.2-6.7) for the ruxolitinib arm and 2.1 months (95% CI, 1.6-3.2) for the BAT arm; and the median time from first response to death or initiation of new systemic therapies for cGVHD was 25 months (95% CI, 16.8-not estimable) for the ruxolitinib arm and 5.6 months (95% CI, 4.1-7.8) for the BAT arm. Common adverse reactions included anemia, thrombocytopenia, and infections. Given the observed response rate with durability, the clinical benefit of ruxolitinib appears to outweigh the risks of treatment for cGVHD after the failure of one or two lines of systemic therapy.

Regulation of immunotherapeutic products for cancer and FDA's role in product development and clinical evaluation.

Immunotherapeutics include drugs and biologics that render therapeutic benefit by harnessing the power of the immune system. The promise of immune-mediated therapies is target specificity with a consequent reduction in off-target side effects. Recent scientific advances have led to clinical trials of both active and passive immunotherapeutic products that have the potential to convert life-ending diseases into chronic but manageable conditions. Clinical trials investigating immunotherapeutics are ongoing with some trials at advanced stages of development. However, as with many products involving novel mechanisms of action, major regulatory and scientific issues arising with clinical use of immunotherapeutic products remain to be addressed. In this review, we address issues related to different immunotherapeutics and provide recommendations for the characterization and evaluation of these products during various stages of product and clinical development.