Myelofibrosis (MF) is associated with several constitutional symptoms. Currently, there are few therapeutic options for MF. Jaktinib, a novel, small-molecule inhibitor of JAK, is currently being studied for its potential to treat MF. This phase 2 trial investigated efficacy and safety of jaktinib in the treatment of MF patients. The primary end point was the proportion of patients with ≥35% reduction in spleen volume (SVR35, proportion of patients with ≥35% reduction in spleen volume) at week 24. The secondary end points included improvement of anemia, rates of symptom response, and safety profile. Between January 8, 2019 and August 29, 2020, 118 patients were recruited and treated with either jaktinib 100 mg BID or 200 mg QD. At week 24, 54.8% (34/62) of patients in the 100 mg BID group and 31.3% (15/48) in the 200 mg QD group achieved SVR35 (p = .0199). Jaktinib treatment increased hemoglobin level to ≥20 g/L in 35.6% (21/59) of patients with hemoglobin ≤100 g/L at baseline. The proportion of patients who achieved a ≥50% improvement in total symptom score at week 24 was 69.6% (39/56) in the BID group and 57.5% (23/40) in the QD group. The most common ≥ grade 3 hematological treatment-emergent adverse events (TEAEs; ≥ 10%) were anemia (100 mg BID: 24.2%, 200 mg QD: 28.8%), thrombocytopenia (16.7%, 11.5%), and neutropenia (3.0%, 11.5%). All non-hematological TEAEs were mild. These results indicate that jaktinib can shrink the spleen, improve anemia, and other clinical symptoms with good tolerability.

The identification of genetic risk subgroups of T‐cell acute lymphoblastic leukemia (T‐ALL) may provide evidence for risk stratification and individualized treatment. We investigated the characteristics and prognostic value of tumor suppressor gene CDKN2A deletions in 101 patients with T‐ALL. The CDKN2A deletion was present in 23% (23/101) of T‐ALL by fluorescence in situ hybridization (FISH). The most common type of CDKN2A deletion was homozygous deletion (70%, 16/23). A lower frequency of CDKN2A deletion was found in patients with early T‐cell precursor (ETP) ALL than in patients with non‐ETP‐ALL (10.4% vs 34.0%; P = .008). Deletion of CDKN2A was significantly associated with younger age (P = .001), higher white blood cell (WBC) count (P < .001) and higher lactate dehydrogenase (LDH) level (P = .002). Patients with CDKN2A deletion had lower 2‐year overall survival (OS) and event‐free survival (EFS) rates than patients without CDKN2A deletion (2‐year OS: 18.6% ± 8.9% vs 47.4% ± 6.2%, P = .032; EFS: 16.4 ± 8.3 vs 38.6 ± 5.9%, P = .022). In multivariable analysis, CDKN2A deletion was an independent adverse prognostic factor for OS (P = .016). In conclusion, adult T‐ALL patients with CDKN2A deletion had a poor prognosis, and these patients might benefit from intensive chemotherapy or allogeneic hematopoietic stem‐cell transplantation.

Summary Minimal residual disease (MRD) is an important independent prognostic factor for relapse and survival in acute lymphoblastic leukaemia (ALL). Compared with adult B‐cell ALL, reports of adult T‐cell ALL (T‐ALL) MRD have been scarce and mostly based on molecular methods. We evaluated the prognostic value of multiparameter flow cytometry (FCM)‐based MRD at the end of induction (EOI‐MRD). The present retrospective study included 94 adult patients with T‐ALL. MRD was detected by six‐ to eight‐colour FCM. Patients who were EOI‐MRD positive had a higher cumulative incidence of relapse (CIR) (87·6% vs. 38·8%, P = 0·0020), and a lower relapse‐free survival (RFS) (5·4% vs. 61·0%, P = 0·0005) and overall survival (OS) (32·7% vs. 69·7%, P < 0·0001) than those who were EOI‐MRD negative. Moreover, for patients who received allogeneic haematopoietic stem cell transplantation (allo‐HSCT) at their first remission, EOI‐MRD positivity was predictive of post‐transplant relapse (2‐year CIR: 68·2% vs. 4·0%, P = 0·0003). Multivariate analysis showed that EOI‐MRD was an independent prognostic factor for CIR [hazard ratio (HR) 2·139, P = 0·046], RFS (HR 2·125, P = 0·048) and OS (HR 2·987, P = 0·017). In conclusion, EOI‐MRD based on FCM was an independent prognostic factor for relapse and survival in adult T‐ALL. For patients who underwent HSCT, EOI‐MRD could be used to identify patients with a high risk of relapse after allo‐HSCT.

No abstract

Although ruxolitinib improves splenomegaly and constitutional symptoms in patients with myelofibrosis (MF), a substantial proportion of patients discontinue ruxolitinib because of intolerance. This phase 2 trial investigated the safety and efficacy of jaktinib, a novel JAK inhibitor in patients with ruxolitinib‐intolerant MF. The primary endpoint was the proportion of patients with ≥35% reduction in spleen volume (SVR35) at week 24. The secondary endpoints included change of MF‐related symptoms, anemic response, and safety profiles. Between December 18, 2019, and November 24, 2021, 51 patients were enrolled, 45 treated with jaktinib 100 mg bid (100 mg bid group) and six received non‐100 mg bid doses (non‐100 mg bid group). The SVR35 at week 24 in the 100 mg bid group was 43.2% (19/44, 95% CI 29.7%–57.8%). There were 41.9% (13/31) of transfusion‐independent patients with hemoglobin (HGB) ≤100 g/L who had HGB elevation ≥20 g/L within 24 weeks. The proportion of patients with a ≥50% decrease in the total symptom score (TSS 50) at week 24 was 61.8% (21/34). The most commonly reported grade ≥3 treatment‐emergent adverse events (TEAEs) in the 100 mg bid group were anemia 31.1%, thrombocytopenia 22.2%, and infectious pneumonia 17.8%. A total of 16 (35.6%) in the 100 mg bid group had serious adverse events, and 4 (8.9%) were considered possibly drug related. These results indicate jaktinib can provide a treatment option for patients with MF who are intolerant to ruxolitinib.

7015 Background: Ruxolitinib and HU are recommended by Chinese MF guideline for splenomegaly. There is an unmet need for new treatments. Jaktinib, a novel JAK and AVCR1 inhibitor, showed promising activity on splenomegaly, anemia, and MF symptoms in a phase 2 study (NCT03886415). Here we present the interim results of a phase 3 study, which assessed the efficacy and safety of jaktinib compared to HU. Methods: Pts aged ≥ 18 with primary or post-ET/PV MF, DIPSS Int-2 or high risk, and no prior or ≤10 days’ treatment with a JAK inhibitor were enrolled and randomly assigned (2:1) to receive jaktinib 100 mg bid plus HU placebo or HU 0.5g bid plus jaktinib placebo, stratified by DIPSS risk status (Int-2 or high risk). One interim analysis was pre-specified to be conducted when 70 pts completed the week (wk) 24 visit or met the criteria for treatment termination before wk 24. The primary endpoint was the proportion of pts with a spleen volume reduction of ≥ 35% from baseline (SVR35) at wk 24, measured by MRI/CT images and assessed centrally. Secondary endpoints included the best spleen response rate (defined as achieving SVR35 at any time), the proportion of pts with a ≥ 50% reduction in Total Symptom Score (TSS50), improvement of anemia, safety, etc. Results: This interim analysis (cut-off: April 8, 2022) included 47 pts receiving jaktinib and 23 receiving HU. 66.0% (jaktinib) and 69.6% (HU) had a baseline hemoglobin (Hb) < 100 g/L. 59.6% (jaktinib) and 69.6% (HU) were JAK2V617F positive. The SVR35 rates at wk 24 were 72.3% for jaktinib vs. 17.4% for HU ( p≤0.0001). The best spleen response rates were 80.9% of jaktinib-treat pts vs. 26.1% of HU-treated pts ( p≤0.0001). The median maximum percentage change from baseline in spleen volume were -46.59% vs. -18.50%. The TSS50 rates at wk 24 were 63.8% for jaktinib vs. 43.5% for HU ( p = 0.1163). 5 of 7 jaktinib-treated and two of 5 HU-treated pts who required RBC transfusion at baseline achieved a ≥50% decrease in RBC transfusion by wk 24. In transfusion-independent pts with baseline Hb ≤100 g/L, 39.3% for jaktinib and 15.4% for HU had a ≥20 g/L Hb increase. The most common grade ≥3 hematological treatment emergent adverse events (TEAEs) (jaktinib vs. HU) were anemia (25.5% vs. 43.5%), thrombocytopenia (17.0% vs. 39.1%), leukopenia (2.1% vs. 21.7%), neutropenia (2.1% vs. 21.7%) and decreased lymphocyte count (2.1% vs. 13.0%). Most common non-hematological TEAEs were upper respiratory tract infection (21.3% vs. 21.7%), elevated bilirubin (12.8% vs. 26.1%), fever (12.8% vs. 21.7%) and diarrhea (10.6% vs. 21.7%), predominantly of grade 1 or 2. TEAEs leading to treatment discontinuation occurred in 8.5% of jaktinib and 17.4% of HU. Conclusions: Jaktinib demonstrated significant clinical benefits over HU in MF pts for spleen response with improved symptom response and less cytopenias. Jaktinib may be a new treatment option for MF pts, especially for those with anemia. Clinical trial information: NCT04617028 .

Ruxolitinib has demonstrated efficacy in patients with myelofibrosis (MF). However, substantial number of patients may not respond after 3–6 months of treatment or develop resistance over time. In this phase 2 trial, patients with a current diagnosis of intermediate or high‐risk MF who either had an inadequate splenic response or spleen regrowth after ruxolitinib treatment were enrolled. All patients received jaktinib 100 mg Bid. The primary endpoint was the proportion of patients with ≥35% reduction in spleen volume (SVR 35) at week 24. The secondary endpoints included change of MF‐related symptoms, anemic response, and safety profile. From July 6, 2021, to January 24, 2022, 34 ruxolitinib‐refractory or relapsed patients were enrolled, 52.9% (18 of 34) were DIPSS intermediate 2 or high risk. SVR 35 at week 24 was 32.4% (11 of 34, 95% CI 19.1%–49.2%) in all patients and 33.3% (6 of 18, 95% CI 16.3%–56.3%) in the intermediate 2 or high‐risk group. A total of 50% (8 of 16) transfusion‐independent patients with hemoglobin (HGB) <100 g/L at baseline had HGB elevation ≥20 g/L within 24 weeks. Furthermore, 46.4% (13 of 28) of patients had a ≥ 50% decrease in the total symptom score (TSS 50) at week 24. The most common grade ≥3 treatment‐emergent adverse events (TEAEs) were thrombocytopenia (32.4%), anemia (32.4%), and leukocytosis (20.6%). In total, 13 (38.2%) of 34 patients had serious adverse events (SAE), of which drug‐related SAEs were found in 5 patients (14.7%). These results indicate that jaktinib can be a promising treatment option for patients with MF who have either become refractory to or relapsed after ruxolitinib treatment.

No abstract