Written in Blood
The TRUTH About Ruxolitinib in Thalassemia : Lower Transfusion Burden , No Improvement in Hemoglobin
In an update from the phase IIa TRUTH study evaluating ruxolitinib in patients with transfusion-dependent thalassemia , investigators reported that treatment with the JAK1 / 2 inhibitor led to a reduction in red blood cell ( RBC ) transfusion dependence and spleen volume from baseline , though there were no clinically relevant improvements in patients ’ pretransfusion hemoglobin levels . Ali T . Taher , MD , PhD , of the American University of Beirut Medical Center in Lebanon , and co-authors published their findings in a Letter to the Editor in Blood . Based on results from a preclinical study demonstrating that thalassemic erythroid cells showed upregulation of JAK2 , the single-arm , open-label , multicenter TRUTH study evaluated the safety and efficacy of ruxolitinib in 30 patients ( 27 with beta-thalassemia and 3 with E beta-thalassemia ) who required RBC transfusions .
Patients included in the study were on a regular transfusion regimen ( requiring ≥2 RBC units within 4-week intervals for 24 weeks prior to enrollment ) and had an enlarged spleen ( ≥450 cm 3 confirmed by magnetic resonance imaging or computed tomography scan ). Patients were excluded if they had received splenectomy prior to enrollment , had a pretransfusion hemoglobin of < 65 g / L , had platelet counts < 75 × 10 9 / L , or had been previously treated with any JAK inhibitor .
The study included a 30-week treatment phase and an extension phase for patients who benefitted from ruxolitinib at the end of 30 weeks . Ruxolitinib was administered at a starting dose of 10 mg twice-daily ; the dose could be increased by 5 mg to a maximum of 25 mg twicedaily if spleen volume was reduced by less than 50 percent from baseline by 30 weeks .
Twenty-six patients completed the 30 weeks of treatment , and four discontinued early because of adverse events ( AEs ; n = 2 ), withdrawal of consent ( n = 1 ), or patient / guardian decision ( n = 1 ). Eighteen patients entered the extension phase , four of whom discontinued the study early .
The safety profile of ruxolitinib in this study was consistent with previous reports , and most AEs were grade 1 or 2 in severity . The most common allgrade AEs were upper respiratory tract infection ( n = 8 ; 27 %); nausea ( n = 6 ; 20 %); and diarrhea , upper abdominal pain , and weight gain ( n = 5 ; 17 % for all ). Five patients ( 17 %) reported grade 3 or 4 anemia . Serious AEs deemed related to ruxolitinib included pneumonia ( n = 1 ), viral pneumonia ( n = 1 ), drug-induced hepatitis ( n = 1 ), and pyrexia ( n = 1 ).
In the primary analysis , which included the 27 patients who received at least 18 weeks of treatment , the researchers observed a mean 5.9 percent decrease in RBC transfusion requirement ( 95 % CI – 14.7-2.8 ) from baseline :
• 12 patients showed a decrease in RBC volume
• 7 showed an increase
• 8 showed no change
At week 30 , 24 patients had evaluable spleen size measurements , and there was a consistent observed reduction in spleen size from baseline , at a median of 22.5 percent by week 12 ( range = – 44.3-34.5 %; n = 26 ) and 26.4 percent by week 30 ( range = – 64.3-8.5 %; n = 25 ). “ Except [ for ] one patient who was off study at week 30 due to AEs of anemia and upper respiratory tract infection , all patients were able to achieve at least some degree of spleen volume reduction with ruxolitinib
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32 ASH Clinical News