What are the best treatments for PV today?

 

What are the most promising treatments for PV / MPN today?

1. COMBINE PHLEBOTOMY AND ASPIRIN

In Polycythemia Vera (PV), an increased red blood cell mass raises the risk of thrombosis and cardiovascular death. Reducing the risk of blood clots (thrombosis) can be achieved by taking aspirin and maintaining hematocrit levels within the range recommended by your physician (<45 or <42). 

Phlebotomy: The study, conducted by Marchioli et al., examined the effects of different treatment intensities in patients with JAK2-positive polycythemia vera. A total of 365 adults were randomly assigned to receive either more intensive treatment (target hematocrit <45%) or less intensive treatment (target hematocrit 45-50%). The study concluded that patients with a hematocrit target of less than 45% had significantly lower rates of cardiovascular death and major thrombosis than those with a hematocrit target of 45-50%.

Aspirin: A double-blind, placebo-controlled, randomized trial involving 518 patients with polycythemia vera assessed the safety and efficacy of low-dose aspirin (100 mg daily) for preventing thrombotic complications. The study found that aspirin reduced the risk of the combined end point of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes (relative risk, 0.41; 95 percent confidence interval, 0.15 to 1.15; P=0.09) and the risk of the combined end point of nonfatal myocardial infarction, nonfatal stroke, pulmonary embolism, major venous thrombosis, or death from cardiovascular causes (relative risk, 0.40; 95 percent confidence interval, 0.18 to 0.91; P=0.03). However, overall mortality and cardiovascular mortality were not significantly reduced. 

Evidence from other cancers: Aspirin has shown promise in generally improving cancer outcomes and reducing metastatic spread, particularly for localized or regional tumors. Studies have found that post-diagnosis aspirin use is associated with improved survival in various cancers, particularly before any metastasis.

2. UTILIZE INTERFERON TREATMENT

Interferon-alpha drugs, such as Pegasys or Besremi, can help eliminate PV cancer stem cells, may improve life expectancy in PV patients, reduce the risk of myelofibrosis (MF) and clots, especially when started early. (ref, ref, ref)

Healthy hematopoietic stem cells are necessary to sustain healthy immunity and a healthy life. Interferon is currently our best chance to maintain a healthy hematopoietic stem cell population. Interferon in PV is disease modifying; it leads to bone marrow improvement & complete normalization in a subset of users. Interferon treatment results in a significant reduction of JAK2V617F mutated clone in a majority of PV patients. Normal lifespan with PV is possible, when interferon is started early.

3. ADOPT A MEDITERRANEAN OR LOW-CARB DIET

Based on studies, the Mediterranean diet is ideal for PV patients, involving the consumption of ample olive oil or nuts, fish every other day, and limited refined carbohydrates & saturated fat. Based on my personal experience, a low-carb (keto) diet is very effective for controlling blood counts and symptoms if followed consistently. 

4. CONSUME DAILY GREEN TEA FOR CONTROLLING JAK2 

Daily consumption of hot green tea or its extract, epigallocatechin-3-gallate (EGCG), has been reported to inhibit JAK/STAT pathway across multiple blood cancers and autoimmune conditions. A 2018 study found that EGCG reduces JAK2 expression in chronic myeloid leukemia (CML) cells. A 2013 clinical trial showed that 69% of patients with asymptomatic CLL had a biological response to EGCG.  EGCG supplementation induced complete molecular remission in a chronic lymphocytic leukemia case. Furthermore, EGCG has been found to inhibit specific IFN-γ pathways and JAK2 in alopecia areata (an autoimmune disorder that causes hair loss) patients (2018). It also demonstrated potential in vitiligo (an autoimmune skin condition) treatment by inhibiting JAK2 kinase activity (2015) A clinical trial sponsored by the National Cancer Institute showed that 69% of patients with asymptomatic CLL had a biological response to EGCG, encouraging the use of green tea for various indolent low-grade B-cell lymphomas.

I drink 1 large coffee mug of Green Tea and Hibiscus Tea daily, brewed together. I find the combination essential to improve my mood and help resolve the depressive side effects of Pegasys.

5. CONSUME OTHER JAK2-INHIBITING DRINKS AND FRUITS

Fruits like strawberry, blackberry, pomegranate which contain JAK2-inhibiting anthocyanins, may be highly beneficial for PV patients. Consuming several portions per day, berry powders in hot water, or pomegranate supplements may be beneficial. 

6. MAINTAIN A HEALTHY BODY WEIGHT & CONSIDER METFORMIN

To effectively reduce the risk of cardiovascular complications associated with PV, it’s crucial to maintain a healthy body weight.  If you are obese and cannot lose weight, consider medication. Metformin helps with weight loss if you have insulin resistance. Plus, Metformin has been shown to have strong anti-cancer effects. Other recent drugs, too, work extremely well for weight loss: Tirzepatide 22.5%, Semaglutide 17%.

Metformin: A 2018 study investigated the effects of metformin, a biguanide with selective antineoplastic activity, on JAK2V617F-positive myeloproliferative neoplasms (MPN) and compared it with the JAK1/2 inhibitor ruxolitinib. Metformin treatment significantly reduced cell viability, proliferation, clonogenicity, and cellular oxygen consumption in JAK2V617F-expressing cell lines. Metformin also reduced cyclin D1 expression and phosphorylation of several proteins. Combining metformin with ruxolitinib resulted in greater reduction of cell viability and increased apoptosis compared to monotherapy. Metformin effectively reduced tumor burden and splenomegaly in MPN mice models and spontaneous erythroid colony formation in primary cells from polycythemia vera patients. The study concluded that metformin has multitarget antileukemia activity in MPN, including downregulation of JAK2/STAT signaling and mitochondrial activity, and may offer alternative or complementary therapeutic strategies for MPN.

A 2019 open-label phase II trial studied the effects of metformin on primary myelofibrosis (PMF) patients, focusing on bone marrow fibrosis, inflammation mediators, and JAK-STAT pathway activation. Eleven non-diabetic adult PMF patients received metformin for a median of 10 months. Preliminary results showed a trend in bone marrow collagen reduction and downregulation of genes associated with MPN phenotype, but the results were not statistically significant. Metformin was found to be safe and well-tolerated.

I personally found off-label Metformin very helpful against MPN and Tirzepatide very helpful for weight loss. 

7. MANAGE CHOLESTEROL LEVELS & CONSIDER A STATIN

If your LDL cholesterol is high, consider taking a cholesterol-lowering medication. Statins have been shown to be associated with longer life in PV. They’re also associated with improved hematocrit control. A remarkable hematological and molecular response was seen in a patient with polycythemia vera during a combination therapy with simvastatin and alendronate. Try a different statin drug or dose if the first one you tried didn’t work for you. 

8. CONTROL BLOOD PRESSURE & CONSIDER AN ACE INHIBITOR

For blood pressure at or above 130/85, consider blood pressure medication, as some drugs (ACE inhibitors) have been shown to prevent spleen enlargement and fibrosis in MF in mice. 

9. CONSIDER SUPPLEMENTING WITH ANTIOXIDANTS

Antioxidant supplements like NAC and astaxanthin may help control blood values and alleviate fatigue symptoms. Sources: (ref, ref, ref, ref)

10. SUPPORT ANTI-INFLAMMATORY PROCESSES & CONSIDER A LEUKOTRIENE INHIBITOR

Managing inflammation through interferon, statins, and supplements like Curcumin, NFR2 activators, and fish oil may improve disease control in PV patients. Resveratrol has been shown to specifically inhibit JAK2v617F cells. Leukotriene Inhibitors like Montelukast may work wonderfully against MPNs. Several folks have had success with 4 herb synergy. Wobenzym may help with symptoms. Sources:  (ref, ref, ref)

11. AVOID THE FOLLOWING

Iron supplements & Vitamin C supplements (increases the absorption of iron).

Always consult with your doctor before making any changes to your drugs or supplements.