Safety and efficacy of jaktinib (a novel JAK inhibitor) in patients with myelofibrosis who are relapsed or refractory to ruxolitinib: A single-arm, open-label, phase 2, multicenter study.

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.

Safety and efficacy of jaktinib (a novel JAK inhibitor) in patients with myelofibrosis who are intolerant to ruxolitinib: A single-arm, open-label, phase 2, multicenter study.

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.

Systemic vasculitis successfully treated with decitabine in a high-risk myelodysplastic syndrome patient: a case report and literature review.

Aim: Epidemiological studies have reported the association between myelodysplastic syndrome (MDS) and autoimmune diseases (AIDs). Immune dysregulation appears as the common driving force between MDS and AIDs pathogenesis. Low-dose hypomethylating agents might suppress tumor growth and regulate immune balance via its epi-immunomodulatory role. Materials & methods: A high-risk MDS patient presented with systemic vasculitis and was successfully treated with ultra-low-dose decitabine (7 mg/m2/d for 5 days). Results: He achieved complete remission of both MDS and AIDs after two cycles of decitabine treatment, and his overall survival duration was 45 months. Conclusion: Future studies should assess the application of ultra-low-dose decitabine among some high-risk MDS patients, especially among those with comorbid AIDs or in cases warranting the prevention of decitabine-mediated myelosuppression.

[Therapeutic effects of combination of arsenic trioxide with low-dose all-trans retinoic acid on induction of remission acute promyeloeytic leukemia].

OBJECTIVE: To observe the therapeutic efficacy and side effects of arsenic trioxide (As2O3)combined with low-dose all-trans retinoic acid (ATRA) on remission induction in newly-diagnosed and relapsed patients with acute promyeloeytic leukemia (APL). METHODS: 224 patients of APL, 156 newly diagnosed patients, aged 34 (13 approximately 62), with a male/female ratio of 1.56, and 28 relapsed patients, aged, aged 34 (12 approximately 63), with a male/female ratio of 1.89, underwent As2O3 + ATRA therapy. The therapeutic effects was compared with that of As2O3 alone treatment on 40 newly diagnosed patients and 25 relapsed patients and that of ATRA alone treatment on 36 newly diagnosed patients and 15 relapsed patients. The treatment protocol for the combination group was as following: As2O3 was administered intravenously at a dose of 10 mg/day and ATRA was given orally three times per day at a dose of 10 mg. The complete remission (CR) rate, period to CR, incidence of early death and side effects were observed in the three groups. RESULTS: In the newly-diagnosed patients, there was no significant difference in CR rate among the three groups (92.5% for the As2O3/LD-ATRA group, 83.8% for the ATRA group, and 90% for the As2O3 group respectively). In comparison with As2O3 alone, administration of LD-ATRA to the patients in the As2O3/LD-ATRA group significantly shortened the period to CR (the medium time to CR was 28 days for the As2O3/LD-ATRA group and 39 days for the As2O3 group respectively). As compared to ATRA alone, treatment with As2O3 with low-dose ATRA showed a significantly lower incidence of early death (2.5% for the As2O3/LD-ATRA group and 13.9% for the ATRA group respectively). In the relapsed patients, the CR rate was significantly higher in the group treated with As2O3/LD-ATRA (71.4% for the As2O3/LD-ATRA group, 32.0% for the ATRA group, and 43.0% for the As2O3 group respectively). The combined use of LD-ATRA with As2O3 did not further enhance toxic side effects as compared to As2O3 alone or ATRA alone. CONCLUSION: As2O3/LD-ATRA regimen is superior to either regimen given alone to patients with APL. It is an efficient therapeutic approach to APL patients using a combination of As2O3 with low-dose ATRA.

An efficient therapeutic approach to patients with acute promyelocytic leukemia using a combination of arsenic trioxide with low-dose all-trans retinoic acid.

The use of arsenic trioxide (As2O3, ATO) combined with all-trans retinoic acid (ATRA) has recently been reported to induce remission in patients with acute promyelocytic leukemia (APL). However, its efficiency remains inconclusive mainly due to the small number of the available cases. In this study, therefore, we present a clinical study using a combination of ATO with low-dose ATRA (LD-ATRA) to treat 108 APL patients (80 newly diagnosed patients, 28 relapsed patients). Therapeutic outcomes using the ATO/LD-ATRA approach were compared with those of APL patients treated either with ATO alone (65 patients) or ATRA alone (51 patients). The results showed that the ATO/LD-ATRA approach provided significantly better therapeutic outcomes as compared to either ATO or ATRA alone, as evidenced by lower mortality, a higher CR rate and a reduced period to CR. In addition, the toxic side-effects have been no worse with the combined ATO/LD-ATRA treatment than with either ATO or ATRO alone and in some cases have been reduced. These data suggest that the ATO/LD-ATRA regimen is superior to either regimen given alone to patients with APL.