Phase 3 Trials: REACH2 and GRAVITAS-301

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Usama Gergis, MD: Let me comment on 2 very interesting trials with recently reported results. The REACH2 trial is a multicenter, phase 3 trial in patients with steroid-refractory acute graft-versus-host disease [GVHD] comparing ruxolitinib plus steroids versus best available treatment and steroids. Just like REACH1, the primary end point is overall response rate at day 28. The results of this very important trial were recently announced, and the trial reached the primary end point of overall response rate at day 28.

A paradox to this is the GRAVITAS-301 trial, which compared itacitinib, a JAK1 inhibitor in patients with chronic graft-versus-host disease versus placebo. The patients had chronic GVHD and were receiving itacitinib plus steroids versus placebo plus steroids, and there were no statistically significant responses. Let me take that back. There were no statistically significant differences in resolution of chronic graft-versus-host disease between the 2 arms or survival data. REACH2 is for [patients with] acute steroid-refractory [disease], and GRAVITAS-301 is for chronic GVHD. REACH2 is a blockbuster. GRAVITAS-301 is a bust.

Transcript edited for clarity.

Case Overview:

Initial presentation

  • A 61-year old man presented with a generalized pruritic rash, abdominal pain and diarrhea (8-12 BMs/day)
  • PMH: he underwent haploidentical allogeneic hematopoietic-cell transplantation for AML 40 days ago
  • PE: maculopapular erythematous rash on bilateral palms, cheeks, ears and upper back (rash involvement >50% of skin); abdomen is tender to palpation diffusely

Clinical workup

  • Labs: ANC 0.7 x 109/L, plt 75 x 109/L, total bilirubin 8 mg/dl, AST 54 U/L, ALT 60 U/L
    • Negative for HBV, HBV, CMV, EBV, HHV-6
  • Negative stool tests
  • Flexible sigmoidoscopy with biopsy:
    • Lower GI biopsy showed moderate mixed inflammation in the lamina propria and scattered apoptotic bodies without crypt loss
  • Skin punch biopsy of the back shows hyperkeratosis, hypergranulosis associated with lichenoid inflammatory infiltrate
  • Modified Glucksberg criteria: grade 3; MAGIC criteria: grade III

Treatment

  • Systemic corticosteroids (prednisone 2 mg/kg/day) + topical steroids (triamcinolone)
    • No treatment response after day 5
  • He was started on ruxolitinib 5 mg PO BID, increased to 10 mg PO BID on day 6
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