REACH2 Post Hoc Analysis Shows No Impact of Cytopenias on Ruxolitinib in aGVHD

Zahra Mahmoudjafari, PharmD, BCOP, DPLA

The occurrence of cytopenias was not influenced by the efficacy and dose intensity of treating for ruxolitinib (Jakafi) in patients with steroid-refractory acute graft-vs-host disease (SR-aGVHD), according to a post hoc analysis of the REACH2 trial (NCT029132561) presented at the 2023 Transplantation & Cellular Therapy Meetings.

In REACH2, a randomized, open-label phase 3 study, 302 patients were included in the safety analysis. Among those enrolled, 152 were randomized to receive 10 mg of oral ruxolitinib twice a day while 150 were assigned to 1 of 9 BAT options.

End points observed in the analysis included overall response rate (ORR) at day 28, duration of response, durable responses at day 56 in patients who responded by day 28 by platelet counts, white blood cell counts, hemoglobin, and absolute neutrophil counts.

In the post hoc analysis, treatment with ruxolitinib led to higher responses at day 28 vs treatment with best available therapy (BAT) in most cytopenia-based subgroups. Durable responses were observed at day 56, similar blood counts during early treatment were seen with both ruxolitinib and BAT, and ruxolitinib led to higher ORRs vs BAT in patients 12 years or older with grade II- IV SR-aGVHD at day 28 (62% vs 39%, respectively).

Additionally, the mean platelet counts, and hemoglobin concentrations were similar between groups as they decreased in the first 4-8 weeks of therapy, then recovered after. White blood cell counts, and absolute neutrophil counts also decreased through week 8 and were lower in patients administered ruxolitinib through the analysis compared with BAT at week 24.

In an interview with Targeted Oncology^TM, Zahra Mahmoudjafari, PharmD, BCOP, clinical pharmacy manager at the University of Kansas Health System, discussed the post hoc analysis from the REACH2 trial and highlighted the key takeaways.

Targeted Oncology: Can you discuss the impact of cytopenias in this patient population?

Cytopenias for patients with steroid-refractory aGVHD remains a significant treatment-related complication. Many patients with cytopenias are at risk for adverse events, such as infections.Cytopenias are also challenging in patients who require additional treatment to ensure that we minimize toxicities.

What is the rationale behind this research?

Ruxolitinib was associated with higher response rates vs the best available therapy in the randomized, open-label phase 3 REACH2 trial in patients 12 years and older with grade II-IV SR aGVHD. One common adverse event of ruxolitinib is hematologic toxicity. Thrombocytopenia and anemia were the most common adverse events with ruxolitinib. There are recommended dose adjustments in the package insert and there has been concern for maintaining dose intensity to reach optimal efficacy in this patient population, we sought to determine the outcomes of REACH2 patients who developed clinically relevant cytopenias.

What can you tell me about the REACH2 post hoc analysis?

This post-hoc analysis utilized data from REACH2 and analyzed overall response rate at day 28, duration of response and durable response at day 56 among Day 28 responders. Laboratory values were assessed at baseline, weekly through week 8, and every 4 weeks through Week 24. 309 patients were randomized in REACH2 and 302 were included in this post-hoc analysis.

What are the main findings that were presented at the 2023 Transplantation & Cellular Therapy Meetings?

We found that the presence of cytopenias did not impact the favorable efficacy outcomes, overall response rate, and duration of treatment response. It also did not impact our ability to maintain dose intensity of ruxolitinib in these patients. We were able to demonstrate in this post-hoc analysis that despite a concern for cytopenias, ruxolitinib and best available therapy were associated with a similar reduction in blood counts and there is likely an aGVHD effect versus treatment related effects.

What unmet needs still exist in this space?

Steroid refractory acute graft versus host disease remains a significant area of unmet need. Patients unable to tolerate ruxolitinib as a treatment option continues to be a clinical challenge.

REFERENCE

Mahmoudjafari Z, Socie G, Bhatt V, Galvin J, Xue Z, Mohty M. Impact of cytopenias in patients treated with ruxolitinib versus best available therapy for steroid-refractory acute graft-versus-host disease: A REACH2 post hoc analysis. Presented at: 2023 Transplantation & Cellular Therapy Meetings; Orlando, FL; February 15-19, 2023. Poster 344.