Citations

AbstractWe retrospectively reviewed 72 anemic patients with myelofibrosis (MF; median age 68 years), who were JAK2 inhibitor‐naïve at the time of study entry to a phase‐1/2 momelotinib clinical trial. Driver mutation profile included JAK2 69%, CALR 17%, MPL 8%, and triple‐negative 6%; other mutations included ASXL1 39% and SRSF2 17%. Momelotinib was administered at a median dose of 300 mg daily. Anemia response was assessed by formal criteria and documented in 44% of all patients with hemoglobin levels below the sex‐adjusted reference range (n = 72), 48% of those with hemoglobin <10 g/dl (n = 54), and 46% of those who were transfusion‐dependent at the time of study entry (n = 28). Anemia response was more likely with post‐essential thrombocythemia MF (83% vs 37%; p = .001), lower serum ferritin (p = .003), and shorter time from diagnosis to momelotinib therapy (p = .001); the first two variables were also predictive in transfusion‐dependent patients. Post‐momelotinib median survival was 3.2 years; in univariate analysis, survival was superior in anemia responders (median 3.8 vs. 2.8 years; p = .14) and in the presence of type 1/like CALR mutation and inferior in the presence of age > 65 years, ASXL1/SRSF2 mutation, unfavorable karyotype, DIPSS‐plus high risk, red cell transfusion need and higher serum ferritin. Multivariable analysis confirmed the favorable impact of anemia response on survival (p = .02; HR 0.5, 3/5/10‐year survival; 69%/38%/25%). This survival advantage was also noted in transfusion‐dependent patients (3.7 vs. 1.9 years; p = .01; HR 0.3) and appeared to be restricted to patients with an unfavorable genetic profile. The current study suggests a short‐term survival benefit associated with anemia response in momelotinib‐treated patients with MF.

BACKGROUND: ARDS is a serious complication of hematopoietic stem cell transplant (HSCT). Pre-transplant risk factors for developing ARDS after HSCT have been recently identified. The objective of this study was to better understand post-transplant risk factors for developing ARDS after HSCT. METHODS: This was a nested case-control study. ARDS cases were matched to hospitalized non-ARDS controls by age, type of transplantation (allogeneic vs autologous), and time from transplantation. In a conditional logistic regression model, any potential risk factors were adjusted a priori for risk factors known to be associated with ARDS development. RESULTS: One hundred and seventy ARDS cases were matched 1:1 to non-ARDS hospitalized controls. Pre-admission, cases were more likely to be on steroids (odds ratio [OR] 1.90 [1.13–3.19], P = .02). At time of admission, cases had lower platelet count (OR 0.95 [0.91–0.99], P = .02), lower bicarbonate (OR 0.94 [0.88–0.99], P = .035), and higher creatinine (OR 1.91 [1.23–2.94], P = .004). During the first 24 h after admission, cases were more likely to have received transfusion (OR 2.41 [1.48–3.94], P < .001), opioids (OR 2.94 [1.67–5.18], P < .001), and have greater fluid administration (OR 1.52 [1.30–1.78], P < .001). During the hospitalization, ARDS cases had higher temperature (OR 1.77 [1.34–2.33], P < .001) and higher breathing frequency (OR 1.52 [1.33–1.74], P < .001). ARDS cases were more likely to have had sepsis (OR 68.0 [15.2–301.7], P < .001), bloodstream infection (OR 4.59 [2.46–8.57], P < .001), and pneumonia (OR 9.76 [5.01–19.00], P < .001). CONCLUSIONS: Several post-transplant predictors of ARDS development specific to the HSCT population were identified in the pre-hospital and early in-hospital domains. These findings can provide insights into causal mechanisms of ARDS development and be used to develop HSCT-specific risk prediction models.

Abstract The standard primary treatment for acute graft-versus-host disease (GVHD) requires prolonged, high-dose systemic corticosteroids (SCSs) that delay reconstitution of the immune system. We used validated clinical and biomarker staging criteria to identify a group of patients with low-risk (LR) GVHD that is very likely to respond to SCS. We hypothesized that itacitinib, a selective JAK1 inhibitor, would effectively treat LR GVHD without SCS. We treated 70 patients with LR GVHD in a multicenter, phase 2 trial (NCT03846479) with 28 days of itacitinib 200 mg/d (responders could receive a second 28-day cycle), and we compared their outcomes to those of 140 contemporaneous, matched control patients treated with SCSs. More patients responded to itacitinib within 7 days (81% vs 66%, P = .02), and response rates at day 28 were very high for both groups (89% vs 86%, P = .67), with few symptomatic flares (11% vs 12%, P = .88). Fewer itacitinib-treated patients developed a serious infection within 90 days (27% vs 42%, P = .04) due to fewer viral and fungal infections. Grade ≥3 cytopenias were similar between groups except for less severe leukopenia with itacitinib (16% vs 31%, P = .02). No other grade ≥3 adverse events occurred in &gt;10% of itacitinib-treated patients. There were no significant differences between groups at 1 year for nonrelapse mortality (4% vs 11%, P = .21), relapse (18% vs 21%, P = .64), chronic GVHD (28% vs 33%, P = .33), or survival (88% vs 80%, P = .11). Itacitinib monotherapy seems to be a safe and effective alternative to SCS treatment for LR GVHD and deserves further investigation.