Early and first-line initiation of Rucotinib treatment has significant benefits

In the first two phases, we have combed and summarized the survival benefits of rucotinib in the treatment of myelofibrosis (MF) patients and real-world data, and further clarified: rucotinib treatment in MF patients can not only shrink the spleen and improve systemic symptoms It can also significantly prolong the overall survival of MF patients and reverse myelofibrosis, and is safe and effective in real-world clinical practice
.

Knowing the efficacy of rucotinib, you may be wondering how to grasp the timing of rucotinib treatment? Do you start treatment with Rucotinib after diagnosis or wait until other drugs are not tolerated? Can patients with early treatment get better treatment benefits? Let's take a look at the content of this issue! Patients with early fibrosis PMF have good therapeutic efficacy and tolerability.
Primary myelofibrosis (PMF) can be divided into early fibrosis (pre-PMF, MF≤1) and overt PMF (overtPMF, MF).
≥2), and some researchers directly divide PMF patients into low fibrosis grade (LGF, MF≤1 grade) and high fibrosis grade (HGF, MF≥2 grade) [1-3]
.

The symptoms and characteristics of the two types of patients are different.
Are the responses the same when receiving rucotinib treatment [2]? Let us first look at the results of an analysis of a clinical database created by 20 European Hematology Centers
.

 A total of 232 PMF patients treated with Rucotinib were analyzed [2]
.

Baseline data showed that compared with patients with significant fibrosis, early patients started to use rucotinib with higher hemoglobin (p<0.
001) and platelet count (p=0.
006)
.

Treatment of early fibrosis with rucotinib can obtain high and stable spleen and symptomatic response.
Splenic response: The spleen response rate of patients with early fibrosis at 3 months was significantly higher than that of patients with obvious fibrosis, p=0.
04
.

And over time, the proportion of patients with stable splenic response in early fibrosis patients increased significantly (46.
2% vs 28.
7%, p=0.
02)
.

Symptom response: At all time points, the symptom response rate of patients with early fibrosis was significantly higher than that of patients with obvious fibrosis (Table 1)
.

Table 1 Responses of PMF patients in the early stage of fibrosis and the obvious stage of fibrosis.
Rucotinib treatment in the early stage of fibrosis is less toxic.
Anemia: At the 6th month, compared with the patients in the early stage of fibrosis, the grade of anemia in patients with the obvious stage is significantly increased.
(P=0.
01)
.

Thrombocytopenia: In people without thrombocytopenia (platelet count ≥150x109/L) at the start of rocotinib treatment, patients with early fibrosis have a lower incidence of all grades of thrombocytopenia (p = 0.
01)
.

Among people with thrombocytopenia when starting rucotinib treatment, patients with obvious fibrosis are more likely to have an increase in the grade of thrombocytopenia (Table 2)
.

Table 2 The hematological toxicity related to the treatment of rucotinib in patients with early and obvious fibrosis stage.
A number of JUMP studies have shown that early and first-line initiation of rucotinib treatment has a significant effect.
The JUMP study is the reported treatment of rucotinib so far The phase 3b extension trial with the largest sample size of MF included a total of 2233 MF patients from 26 countries
.

The study aims to evaluate the efficacy and safety of rucotinib outside of clinical trials.
The study design is shown in Figure 1 [4]
.

Figure 1 JUMP study design.
The results of the JUMP study further affirmed the good efficacy and safety of Rucotinib in MF patients, and expanded the applicable population of Rucotinib.
For MF patients with advanced age and advanced (medium-risk-2/high-risk) with hematological abnormalities, rucotinib is safe and effective [5-8]
.

 Several subsequent analyses of JUMP studies further confirmed the significant efficacy of early and first-line initiation of Rucotinib in the treatment of MF[4,7-8]
.

 2017 EHA-E1333 | Rucotinib has a significant spleen shrinking effect in the treatment of early (low-risk/medium-risk-1) MF patients, and the adverse reactions are mild.
-2/High-risk) MF patients, and early (DIPSS low-risk/medium-risk -1) patients have more significant spleen shrinking effect with rocotinib treatment [7]
.

Figure 2 The spleen response rate of rucotinib in low-risk/medium-risk-1 and medium-risk-2/high-risk MF patients is the same, and the safety results also show that in early (low-risk/medium-risk-1) MF patients, rucotinib The adverse effects of Nitraria treatment were lighter, and the proportion of patients who insisted on treatment was higher
.

 Table 3 The safety of rucotinib in the treatment of MF patients with different risk strata The analysis of the correlation between baseline patient characteristics and doses and spleen and symptom response showed that ① early (medium risk-1/low risk) rucotinib treatment was initiated, ② rucotinib was used as the first-line treatment, and ③ rucotinib treatment dose >10 mg bid, which is associated with a higher splenic response obtained by rucotinib treatment [8]
.

Figure 3 Multivariate analysis of the efficacy of rucotinib for spleen contraction.
The final result of this analysis was published online in Leuk Lymphoma in 2020, consistent with the report of the 2018 EHA conference, early (medium risk-1/low risk), first-line Initiating rucotinib treatment and maintaining sufficient rucotinib treatment can achieve a higher splenic response rate [4]
.

2021 EHA-EP1092 | Early stage (LGF, ≤2 years after diagnosis) The symptom response and survival benefit of rucotinib treatment are significant.
This year's EHA meeting reported the researcher's analysis of 1326 PMF patients in the JUMP study [3]
.

The researchers divided PMF patients into two groups: LGF (268 cases) and HGF (852 cases)
.

There were more patients with anemia (hemoglobin <100 g/L, 46.
4% vs 32.
5%) and thrombocytopenia (platelets <100x109/L, 8.
6% vs 4.
1%) in the HGF group at baseline.
Other patient characteristics are shown in Table 4
.

Table 4 Baseline characteristic spleen response rate of the two groups of patients: There was a significant negative correlation between MF grade and spleen response at week 24.
The higher the grade, the lower the spleen response rate (grade 0 is 66.
7%, grade 1 is 62.
0 %, 59.
5% for level 2 and 50.
2% for level 3)
.

At the 24th week, the proportion of patients with spleen length reduction ≥50% in the LGF group was higher (62.
4% vs 55.
1%)
.

 Survival rate: The progression-free survival rate (82%) of the LGF group at week 144 was higher than that of the HGF group (70%)
.

Both groups did not reach the median overall survival (OS), and the OS rate at week 144 (87%) in the LGF group was also higher than that in the HGF group (79%)
.

Figure 4 OS curve of the two groups of patients.
In addition, the study investigated the time to start rucotinib treatment after diagnosis
.

The results showed that regardless of the grade of fibrosis, a higher splenic response rate can be obtained by starting rucotinib treatment within 2 years after diagnosis (Table 5)
.

Table 5 Splenic response rate at week 24 Conclusion The emergence of rucotinib has brought great benefits to MF patients, breaking through the situation that previous drug treatments cannot change the natural course of MF patients and cannot reverse myelofibrosis
.

In clinical practice, physicians and patients will face the problem of how to grasp the timing of treatment
.

Through the review of this issue, it is further clarified: ①Early (including pre-PMF, LGF, low-risk/medium-risk-1, ≤2 years after diagnosis) initiation of rucotinib treatment has significant benefits; ②first-line initiation of rucotinib treatment Related to a better spleen response
.

It is hoped that these results can help clinicians to further optimize the use of rucotinib in MF patients
.

References: [1] Chinese Society of Clinical Oncology Guidelines Working Committee, Chinese Society of Clinical Oncology (CSCO) Guidelines for Diagnosis and Treatment of Hematological Malignancies 2021[M].
Beijing: People's Medical Publishing House, 2021:302-303.
[2] Palandri F, Palumbo GA, Abruzzese E, et al.
Impact of 2016 WHOdiagnosis of early and overt primary myelofibrosis on presentation and outcome of 232 patients treated with ruxolitinib[J].
Hematol Oncol, 2019,37(4):418-423.
[3] Palandri F, et al.
2021 EHA.
Abstract: EP1092.
[4] Gupta V, Griesshammer M, Martino B, et al.
Analysis of predictors ofresponse to ruxolitinib in patients with myelofibrosis in the phase 3bexpanded-access JUMP study[J].
Leuk Lymphoma, 2021,62(4):918-926.
[5] Primary analysis of JUMP, a phase 3b, expanded‐access study evaluating the safety and efficacy of ruxolitinib in patients with myelofibrosis, including those with low platelet counts[J].
British Journal of Haematology,2020, 189(5):888-903.
[6] Safety and Efficacy of Ruxolitinib in an Open-Label,Multicenter,Single-Arm, Expanded-Access Study in Patients with Myelofibrosis (MF): An1144-Patient Update[J].
Blood, 2014, 124(21):3197-3197.
[7] Passamonti F, et al.
2017 EHA Abstract: E1333.
[8] Al-Ali H, et al.
2018 EHA.
Abstract: PF616.
MCC number JAK2109619 is valid for 2022-09-07, the data is out of date and deemed invalid
.

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