High Rates of Chronic GVHD Flares after Ruxolitinib Taper or Discontinuation

Ruxolitinib (RUX) is an effective steroid-sparing agent in the treatment of graft versus host disease (GVHD). However, the incidence of flare in GVHD symptoms after withdrawal of RUX can increase morbidity and mortality by failing to regain control of GVHD or ensuing complications from high dose immune suppression (IS). Thus, determining the rate and timing of flares in GVHD after discontinuation (d/c) has practical clinical implications. This is a single center, retrospective analysis of 86 patients (pts) with chronic GVHD who tapered or discontinued RUX between 9/5/17-4/5/25. The primary endpoint was the incidence and timing of GVHD flare within 12 months of RUX withdrawal. Flare was defined as an increase in organ severity by at least 1 stage according to NIH Criteria and need for systemic therapy after initial response to RUX with at least stable or mixed response. A cohort was identified based on referrals to the GVHD clinic who were treated with RUX (n=151) and had tapered or discontinued (n=86). Median duration of RUX prior to taper or d/c (whichever was greater) was 337 days (d) (range 28-1531). 38 pts (44%) flared with withdrawal of RUX (9 with taper, 29 with d/c). Average duration of RUX was 542 d with median 270 d prior to taper or d/c. In those who flared, the ORR to initial RUX was 81.5%. Indications to taper included CR (n=6), PR (n=13), infection (n=7), patient pref (pref)/intolerance (intol) (n=5), progression (n=3), and cytopenia (n=4). Pts flared after a median of 91 d. At the time of flare, 22 were off all IS, 21 were on other IS (median 1 line of therapy (LOT)). 15 pts flared in previously or currently involved organs, 23 pts flared in organs not previously affected. 26 pts restarted or increased RUX with flare; 1 had CR, 13 had PR, 1 had mixed response, 6 had no response, and 5 had progression. Pts with no response or progression changed therapies. 12 pts did not resume RUX and proceeded with next line therapy. 48 pts (56%) tapered or discontinued RUX after median 298 d without flare (37 d/c, 11 tapered), with initial ORR of 66.6%. Indication to taper included CR (n=11), PR (n=8), progression (n=11), cytopenia (n=2), relapsed disease (n=8), and pt pref/intol (n=8). At the time of taper or d/c, 23 were off all other IS, 25 remained on other IS (median 1 LOT). Grade ≥3 anemia occurred in 13 pts, ≥3 thrombocytopenia in 7 pts. 1 pt had CMV reactivation, 11 developed pneumonia, 7 had bacteremia, 8 had relapsed disease. No patients expired. In this cohort, 44% of pts who tapered or discontinued RUX developed flare in chronic GVHD. Among those who flared, initial responses to RUX were high with 81.5% ORR, but only 37% had response to resuming RUX. In those who did not flare, initial ORR was lower at 66.6%, and 39.5% of patients discontinued therapy due to progression of GVHD or relapsed disease. These findings suggest continuing RUX in pts with controlled GVHD without indication to taper otherwise.