[2021 ASH Express] Focus on the prognosis study of MPN patients and the whole management of MF patients

In the first five phases, we have combed and summarized the survival benefits of rucotinib in the treatment of myelofibrosis (MF) patients and real-world data.
We also discussed the optimal treatment timing of rucotinib and its application in the peri-transplantation period.

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It has been clear: ①The treatment of MF patients with Rucotinib can not only shrink the spleen and improve the systemic symptoms, but also prolong the overall survival of MF patients and reverse myelofibrosis; ②In actual clinical practice, Rucotinib is safe and effective; ③Early and first-line Initiation of rucotinib treatment has significant benefits; ④The blood cell decline that occurs during the treatment of rucotinib can be solved by the combination of rucotinib; ⑤ the treatment of rucotinib in the peri-transplantation period improves the prognosis of MF patients
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The annual meeting of the American Society of Hematology (ASH) has successfully concluded
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During this conference, a number of research results in the field of myeloproliferative tumors (MPN) and data on the treatment of rucotinib in MF patients were announced, providing further evidence support for the clinical management of MF patients
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Here is a selection of important research features for reference
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Study 1: IPSS score combined with JAK2 mutation can help predict the risk of thrombosis in patients with primary myelofibrosis Title: The Interaction between IPSS Score and JAK2 Mutation Identifies Patients at Different Vascular Risk in Primary Myelofibrosis Abstract Number: 236 (Oral) Overview: This study aims to investigate the thrombosis in patients with primary myelofibrosis (PMF), myelofibrosis secondary to thrombocythemia (PET-MF), and myelofibrosis secondary to polycythemia vera (PPV-MF) Incidence and risk factors, and compared the difference in the incidence of thrombosis between the two groups of patients treated with hydroxyurea (HU) and rucotinib (RUXO)
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Methods: From January 2001 to December 2012, a total of 584 PMF, 207 PET-MF, and 219 PPV-MF patients were included in the European MPN Registration Study
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Results: With a median follow-up of 3.
8 years, 108 patients (10.
7%) had thrombosis, and the overall annual incidence was 2% (95%CI 1.
7~2.
5), of which 50 cases (46.
3%) had arterial thrombosis, 58 cases (53.
7%) ) Is a venous thrombosis
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The annual incidence of thrombosis in PMF, PET-MF and PPV-MF was 1.
91%, 1.
60% and 2.
79%, respectively
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In univariate analysis, the factors that increase the risk of PMF thrombosis were age (P=0.
013) and JAK2 mutation (P=0.
003).
In addition, patients with low-risk and intermediate-risk-1 of IPSS were more likely to have thrombosis in patients with low-risk and intermediate-risk -1 than those with intermediate-risk-2 and high-risk patients.
The risk is higher (P=0.
008)
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To study the relationship between the IPSS score and JAK2 mutations, the researchers created a model, as shown in Figure 1A: JAK2 wild-type and IPSS classified as intermediate-risk-2 or high-risk patients have the lowest cumulative incidence of thrombosis (CIF) (expected The 10-year CIF is 4%; SHR=1), and the patients with JAK2 mutant and IPSS score of low-risk or intermediate-risk -1 have the highest risk of thrombosis (estimated 10-year CIF is 20%, SHR=7.
13, P=0.
008)
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In addition, this study also compared the incidence of thrombosis in the two groups of patients treated with HU (n=470) and Ruxo (n=89).
The annual incidence of thrombosis in the HU group was 2.
40% (95% CI 1.
78~3.
24), Ruxo The annual incidence of thrombosis in the group was 1.
28% (95% CI 0.
48~3.
41) (Figure 1B)
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Figure 1: Regression analysis results based on JAK2 mutation status and IPSS score (A) at the time of diagnosis, and thrombotic competitive risk since the start of treatment (B).
Conclusion: IPSS score combined with JAK2 mutation can help identify patients at risk of thrombosis and prompt appropriate Anti-thrombotic prevention
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RUXO has a tendency to reduce the risk of thrombosis compared with HU in the treatment of MF, but a larger sample study is still needed
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Study 2: Consolidated analysis of Comfort I and II studies: Will early intervention in myelofibrosis affect clinical outcomes? Title: Does Early Intervention in Myelofibrosis Impact Outcomes? a Pooled Analysis of the Comfort I and II Studies Abstract Number: 1505 (Oral and Poster) Purpose: COMFORT I and COMFORT II are RUXO versus placebo (PBO), the best available therapy, respectively (BAT) Phase 3 clinical trial for the treatment of intermediate-risk-2 and high-risk MF patients
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This article combines COMFORT I and II data to evaluate the relationship between the duration of MF disease before treatment and the disease outcome
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Results: A total of 525 patients were enrolled (RUXO: ≤12 months, n=84; >12 months, n=216; PBO/BAT: ≤12 months, n=66; >12 months, n=159)
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Among patients receiving RUXO, patients who started treatment earlier (≤12 months vs >12 months) had fewer thrombocytopenia events, and differences were observed as early as 4-8 weeks of treatment (18% vs 33%) and Over a period of time, a similar trend was observed for anemia events (59% vs 72% in weeks 4-8)
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RUXO treatment for ≤12 months compared with >12 months, the spleen volume decreased more than baseline (24th week, –35%[21] vs –29%[18]; 48th week, –36%[24] vs –28% [22])
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Similarly, patients who started RUXO treatment earlier (≤12 months vs.
>12 months) had a higher rate of spleen volume reduction ≥35% (SVR35) from baseline (week 24, 48% vs 33%; week 48, 44% vs 27%)
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The spleen response was longer than that of patients with a shorter course of disease (median duration of response, less than 230 weeks)
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Compared with patients treated with RUXO for ≤12 months and >12 months: the proportion of patients who reached the total symptom score (TSS) at the 24th week with a reduction of ≥50% (TSS50) from the baseline was higher (56% vs 40%); The average changes from baseline in TSS at 24 weeks were –52% (42) and –44% (51); OS at week 240 was improved (63%[95% CI, 51%~73%] vs 57%[95 CI%, 49% ~ 64%; P = 0.
043]
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regardless of the duration of the disease, RUXO compared with PBO / BAT longer the OS
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Discussion: These results indicate that early initiation of RUXO treatment may improve the clinical outcome of MF patients
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Although young age and high baseline blood cell count may be confounding factors in this study, these factors may reflect the earlier course of the disease
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Although "watch and wait" is still a common strategy for newly diagnosed patients, these data suggest that MF patients may benefit from early intervention
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Figure 2: OS study of MF patients with different disease durations before RUXO treatment 3: REVEAL real-world data analysis: the relationship between elevated blood counts in polycythemia vera and thrombotic events Title: A Real-World Evaluation of the Association between Elevated Blood Counts and Thrombotic Events in Polycythemia Vera (Analysis of Data from the REVEAL Study) Abstract No.
: 239 (Oral) Purpose: This article uses data from the REVEAL study to evaluate the elevated blood counts and thrombotic events (TE) in patients with polycythemia vera (PV).
) Relationship
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Results: A total of 2510 patients were included, and 2271 patients met the conditions of the analysis (77.
9% were high-risk and 22.
1% were low-risk)
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TE occurred in 106 patients, of which 30 patients had arterial TE (the most common was transient ischemic attack [n=15]), and 76 patients had venous TE (the most common was deep vein thrombosis [n=37] ])
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HCT level increased (>45%, hazard ratio [HR]=1.
84[95% CI, 1.
234~2.
749], P=0.
0028), WBC count increased (>11×109/L, HR=2.
35[1.
598~3.
465 ], P<0.
0001) and increased PLT count (>400×109/L, HR=1.
60[1.
088~2.
359], P=0.
0170) are all related to the increased risk of TE (Table 1)
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Compared with WBC count ≥11×109/L, WBC count<7×109/L is associated with high TE risk (HR=2.
61[95% CI, 1.
594-4.
262], P<0.
0001)
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In all models, advanced age, female, and TE history are associated with increased TE risk
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Conclusion: The PV real-world data analysis of the largest sample so far shows that: HCT levels are increased (>45%), WBC counts (>11×109/L), and PLT counts (>400×109/L) are all increased It is related to the increased risk of TE
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These data support the incorporation of blood count values ​​into risk models and clinical treatment decisions for patients with PV
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Table 1: The relationship between blood cell count and TEs.
Literature source: [1]https://ash.
confex.
com/ash/2021/webprogram/Paper145116.
html[2]https://ash.
confex.
com/ash/2021 /webprogram/Paper148509.
html[3]https://ash.
confex.
com/ash/2021/webprogram/Paper150894.
htmlRecommended reading 1.
Repost the "Good News": Rucotinib prolongs the survival of MF patients 2.
Real World data helps the practice of rucotinib medication 3.
Early and first-line start of rucotinib treatment has significant benefits 4.
Rucotinib combination therapy provides new solutions for the treatment of intolerant or drug-resistant MF patients 5.
Peri-transplantation period Rucotinib treatment improves the prognosis of MF patients.
The MCC number JAK21111929 is valid from 2022-11-23, and the data is out of date and deemed invalid
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This information is only for academic reference by medical and health professionals, please do not distribute or forward the stamp "read the original text", we will make progress together