Jaktinib superior to hydroxyurea in myelofibrosis

Jaktinib, a novel JAK and AVCR1 inhibitor, is more effective than hydroxyurea in patients with myelofibrosis, resulting in better spleen response with improved symptom response and less cytopenias, according to the results of a phase III study presented at EHA 2023.

“Jaktinib may be a new treatment option for myelofibrosis patients, especially for those with anaemia,” said the researchers, led by Yi Zhang from Department of Hematology, Zhejiang University School of Medicine, Hangshou, China.

Zhang and colleagues randomized 70 patients (aged ≥18 years) with primary, postpolycythemia vera or postessential thrombocythemia myelofibrosis, dynamic international prognostic scoring system (DIPSS) Int-2 or high risk, and no prior or ≤10 days’ treatment with a JAK inhibitor to receive jaktinib 100 mg bid plus hydroxyurea placebo (n=47) or hydroxyurea 0.5 g bid plus jaktinib placebo (n=23).

A prespecified interim analysis was set when the 70 patients completed the 24-week treatment or met the criteria for the treatment termination before week 24.

The primary endpoint was the proportion of patients with a spleen volume reduction of ≥35 percent from baseline (SVR35) at week 24. Secondary endpoints were the best spleen response rate (defined as achieving SVR35 at any time), the proportion of patients with a reduction of ≥50 percent in Total Symptom Score (TSS50), improvement of anaemia, and safety among others.

In the interim analysis (data cutoff: 8 April 2022), 66.0 percent of patients on jaktinib and 69.6 percent of those on hydroxyurea had a baseline haemoglobin <100 g/L, while 59.6 percent and 69.6 percent were JAK2V617F positive, respectively. Baseline characteristics of the patients were similar between the two treatment arms. [EHA 2023, abstract S212]

At week 24, the SVR35 rates were 72.3 percent for jaktinib and 17.4 percent for hydroxyurea (p≤0.0001). A consistent spleen response benefit was observed with the former over the latter treatment across all subgroups, and the best spleen response rates were 80.9 percent vs 26.1 percent, respectively (p≤0.0001). The median maximum percentage change in spleen volume from baseline were ‒46.59 percent vs ‒18.50 percent.

The TSS50 rates at week 24 were 63.8 percent for jaktinib and 43.5 percent for hydroxyurea (p=0.1163). Five of seven jaktinib-treated and two of five hydroxyurea-treated patients who required red blood cell transfusion at baseline achieved a decrease of ≥50 percent in blood transfusion by week 24. Additionally, one of four patients on jaktinib and none of those on hydroxyurea who were transfusion-dependent at baseline became transfusion-independent.

Among transfusion-independent patients with baseline haemoglobin ≤100 g/L, 39.3 percent and 15.4 percent of those on jaktinib and hydroxyurea, respectively, had a haemoglobin increase of ≥20 g/L.

Adverse events

The most common grade ≥3 haematological treatment-emergent adverse event (TEAE) was anaemia (25.5 percent for jaktinib vs 43.5 percent for hydroxyurea), followed by thrombocytopenia (17.0 percent vs 39.1 percent), leukopenia (2.1 percent vs 21.7 percent), neutropenia (2.1 percent vs 21.7 percent), and decreased lymphocyte count (2.1 percent vs 13.0 percent).

For nonhaematological TEAEs, the most common ones were upper respiratory tract infection (21.3 percent vs 21.7 percent), elevated bilirubin (12.8 percent vs 26.1 percent), fever (12.8 percent vs 21.7 percent), and diarrhoea (10.6 percent vs 21.7 percent), predominantly of grade 1 or 2.

TEAEs that led to treatment cessation occurred more frequently among hydroxyurea-treated than jaktinib-treated patients (17.4 percent vs 8.5 percent).

“Ruxolitinib and hydroxyurea are recommended by Chinese myelofibrosis guideline for splenomegaly,” the researchers said. “Jaktinib … showed promising activity on splenomegaly, anaemia, and myelofibrosis symptoms in a phase II study (NCT03886415).”