Impact of JAK-inhibitor therapy on inflammation-mediated comorbidities in MPNs

by Dr. Hans C Hasselbalch

human  body inflammationChronic inflammation is suggested to contribute to the Philadelphia-chromosome-negative myeloproliferative neoplasm (MPN) disease initiation and progression, as well as the development of premature atherosclerosis and may drive the development of other cancers in MPNs, both nonhematologic and hematologic.

The MPN population has a substantial comorbidity burden, including cerebral, cardiovascular, pulmonary, abdominal, renal, metabolic, skeletal, autoimmune, and chronic inflammatory diseases.

This review describes the comorbidities associated with MPNs and the potential impact of early intervention with anti-inflammatory and/or immunomodulatory agents such as JAK-inhibitors, statins, and IFN-a to inhibit cancer progression and reduce MPN-associated comorbidity impact. Early intervention may yield a subset of patients who achieve minimal residual disease, thereby likely reducing the comorbidity burden and improving the cost-effective socioeconomic profile. *** (This is just the introduction, please click on the “download PDF” or “click to read” below for the entire article)***

Also Note the Publisher’s Summary below the presentation, it covers many of the highlights.

Click here to download PDF

Publisher’s Summary

by David Wallace

As I read the article, there were several points that I found noteworthy:

    • We start to see the term “minimal residual disease” used a bit more often than the less patient friendly 5 (+/-) different forms of remission. Many of us (from a patient perspective) suspect a combination therapy may be the answer in treating MPNs. The usage of JAK inhibitors, IFN and a statin drug sounds like a potent punch.
    • Dr Hasselbalch does note “potential toxicities” surrounding the usage of this combo, as well as concerns over the cost effectiveness over time. The positive aspect of this combo may outweigh the negative implications. We continue to see chronic inflammation involved in MPNs as well as a variety of cancers. Statins were favorably reviewed on a recent article on renal cancer, this looks like an increasing trend in cancer treatment, but remains under debate.
    • Not surprisingly, comorbidities are a concern with MPNs, including bacterial, fungal and viral infections, anemia, cardiovascular, abdominal, as well as development of secondary cancer. The comorbidity profile likely improves with the usage of IFN and JAK inhibitor. Early intervention may result in halting progression of the disease. Not all patients need to be treated early, risk stratification should be personalized.
    • A balanced reality – ET & PV patients may have a shorter survival rate than the general population. The upside is a 5 year view where a potential cure or at least an operation cure/minimal residual disease is foreseen in a large population of ET & PV patients utilizing the combo therapy (IFN, JAK2 inhibitor, statins), if utilized at the time of diagnosis. MF patients using the combo therapy may reverse disease progression, and a subset of patients may see minimal residual disease. It should be noted Dr Hasselbalch has received research grants from Novartis (the European partner for Incyte – Jakafi manufacturer).


About David Wallace

Founder of PV Reporter, a resource for Myeloproliferative Neoplasm (MPN) patients and caregivers. After being diagnosed with Polycythemia Vera (PV) in 2009, I utilized social media to connect with "informed patients" and develop a better understanding of emerging treatment options. My philosophy on patient care is straight forward - "educating the patient is essential, so the patient can guide their physician to meet his or her needs." PV Reporter is a comprehensive resource hub giving visitors vital tools to become "empowered patients."

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