Tag Archives: mpn

Fedratinib and Ruxolitinib: Advice for Deciding Which Agent to Give and When

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The introduction of fedratinib (Inrebic) to the treatment landscape of myelofibrosis (MF) and the challenges that have arisen over deciding between administering fedratinib or ruxolitinib (Jakafi) means more community oncologists should consult specialists when treating these patients, said Andrew Kuykendall, MD.

Research shows that fedratinib and the earlier JAK inhibitor, ruxolitinib have similar efficacy in patients with MF. However, their toxicity profiles differ, and the potential for encephalopathy with fedratinib is an ongoing concern, resulting in a black box warning on the label. Now that the agent is FDA approved for the treatment of MF, oncologists are left with a decision of which JAK inhibitor to give to which patients and when to prescribe them.

How to continue using ruxolitinib now that fedratinib is available remains an unanswered question, said Kuykendall, assistant member, Moffitt Cancer Center; however, experts in treating myeloproliferative neoplasms (MPNs) can be a helpful resource for other oncologists.

Another resource for treatment decision-making is clinical data from the JAKARTA-2 trial, which studied fedratinib in patients with MF who were previously treated with ruxolitinib. Findings from a re-analysis of the study were presented at the 2019 ASCO Annual Meeting and showed that 46 of the 83 assessable patients achieved a spleen response (55%; 95% CI, 44%-66%), meeting the primary endpoint of the study.

The most common adverse events included diarrhea (n = 60), nausea (n = 54), vomiting (n = 40), constipation (n = 20), and others. Additionally, hematologic abnormalities including, grade 3/4 anemia (n = 96), thrombocytopenia (n = 68), and neutropenia (n = 23) were seen. Eighteen patients (19%) discontinued treatment due to adverse events.

These data suggest that fedratinib may be a second-line option for patients who are resistant or sensitive to ruxolitinib. The management of the gastrointestinal (GI)-related toxicities and checking of thymine levels to prevent encephalopathy, however, are newer management concerns that physicians must be aware of when administering fedratinib to patients with MF and is another point when consulting an MPN specialist may come in handy.

Read Targeted Oncology’s interview with Dr. Kuykendall.

Examples of Approved VA Benefits for Vietnam Veterans

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The Department of Veterans Affairs has a search site to look up specific benefit claim cases.  Below are of few examples of MPN-related claims granted (on appeal).

To search the entire VA claims database click here. -for best results be sure to fill in specific illness and search all possible years.

Myelofibrosis

Citation 18101521-Read full report here

FINDINGS OF FACT –

1. An unappealed claim for service connection for myelomonocytic leukemia was denied by the RO in an October 2011 rating decision. The Veteran was notified of the rating decision, but did not appeal.

2. Evidence received since the last final October 2011 rating decision is new and material, and relates to an unestablished fact necessary to substantiate the claim for service connection for myelofibrosis.

3. The Veteran has a current diagnosis of myelofibrosis.

4. The Veteran is presumed to have been exposed to herbicide agents, to include Agent Orange, in service based on his service in the Republic of Vietnam during the Vietnam Era.

5. The medical evidence of record establishes that the Veteran’s myelofibrosis is related to presumed herbicide agent exposure during service.

CONCLUSION OF LAW -New and material evidence has been received to reopen service connection for myelomonocytic leukemia, now claimed as myelofibrosis. The criteria to establish service connection for myelofibrosis are met.

REASONS AND BASES FOR FINDING AND CONCLUSION-(View full report by clicking on citation number above)… This language was included in the Finding…

A letter dated August 2014 from T.A., MD notes that the doctor provided care for the Veteran beginning in 2005 after he was diagnosed with leukemia. Doctor T.A. stated that he reviewed the Veteran’s military records and considered his exposure in Vietnam to Agent Orange. Citing reports by the Institute of Medicine and the Myeloproliferative Neoplasm Research Foundation, Doctor T.A. stated that Agent Orange is a known causative agent of the type of leukemia with which the Veteran was diagnosed. Considering the Veteran’s diagnosis, military and medical records, and the absence of a family history of bone marrow disease, Doctor T.A. opined that it is more likely than not that the Veteran’s leukemia is a direct result of his exposure to Agent Orange during service. 

Citation=0309503-Read full report here

FINDING OF FACT –  There is competent evidence attributing the diagnosis of primary myelofibrosis to the veteran’s service.

CONCLUSION OF LAW –  Primary myelofibrosis was incurred in service.

REASONS AND BASES FOR FINDING AND CONCLUSION-  Although the Veterans Claims Assistance Act of 2000, Pub. L. No. 106-475, 114 Stat. 2096, is applicable to the veteran’s claim, the Board finds that it is unnecessary to address its applicability in this case in view of the disposition reached herein. The veteran’s service records show that his occupational specialty was that of an aircraft engine mechanic during his military career. In 2000, the veteran was diagnosed with primary myelofibrosis. The veteran asserts that he developed this disease due to Agent Orange exposure while in Vietnam.

Citation 0731552-Read full report here

FINDINGS OF FACT:

1. The veteran served on active duty in the Republic of Vietnam during the Vietnam era.

2. He currently has myeloproliferative disorder with myelofibrosis; this condition was initially diagnosed many years after service.

3. Medical evidence is in relative equipoise as to whether the veteran’s myeloproliferative disorder with myelofibrosis was caused by exposure to Agent Orange in service.

 

Background/Analysis:

The veteran has submitted evidence which suggests an association between myeloproliferative disorder with myelofibrosis and exposure to chemicals, such as benzene. He submitted articles which discuss the use of Agent Orange during the Vietnam War. The articles indicate that Agent Orange was a 50-50 mix of two chemicals and that the combined product was mixed with kerosene or diesel fuel and dispersed by aircraft. Other articles note that benzene is a volatile aromatic hydrocarbon which causes various types of leukemia, lymphoma and blood diseases, including myelofibrosis. The greatest risk was to workers who use various petroleum solvents containing benzene such as painters, gasoline distribution workers, refinery workers, chemical workers, rubber workers, printers, newspaper pressworkers and shoe and leather workers. The veteran submitted additional articles regarding herbicide exposure, benzene exposure, dioxins and the health risks associated with exposure to small amounts of chemical benzene.

CONCLUSION OF LAW -Resolving all reasonable doubt in favor of the veteran, myeloproliferative disorder with myelofibrosis was incurred as the result of exposure to Agent Orange in service.

 

Essential Thrombocythemia

Citation 19144431 -Read full report here

FINDINGS OF FACT

1. Resolving reasonable doubt in his favor, the Veteran was exposed to Agent Orange during active service.

2. The Veteran’s thrombocythemia is associated with in-service Agent Orange exposure.

3. The Veteran’s venous stasis ulceration of the bilateral lower extremities is proximately due to his service-connected thrombocythemia

…The Veteran submitted two letters from his treating physicians linking his thrombocythemia to his Agent Orange exposure. An October 2010 letter from the Veteran’s oncologist, Dr. D.B., indicated that the Veteran was diagnosed with thrombocythemia and has been under his care since June 2009. Dr. D.B. wrote that the Veteran was exposed to Dioxin while in Vietnam. He indicated that the Veteran’s diagnosis of essential thrombocytosis was as likely as not related to Dioxin (Agent Orange). A January 2011 letter from Dr. N.B., a hemotologist, indicated that the Veteran was also under her care. Dr. N.B. wrote that the Veteran was exposed to dioxin on different occasions while serving in Vietnam. At the time, she indicated that she was not aware of any studies linking dioxin to essential thrombocythemia but felt that the Veteran’s condition may be as likely as not related to his dioxin exposure.

CONCLUSION OF LAW – Essential thrombocythemia, a form of leukemia, was incurred in active service.

 

Polycythemia Vera

Citation 1414817- Read full report here

FINDINGS OF FACT

1. The Veteran served in the Republic of Vietnam during the Vietnam era, and therefore he is presumed to have been exposed to herbicides.

2. The most probative evidence of record demonstrates that the Veteran’s polycythemia vera is etiologically related to his in-service herbicide exposure.

CONCLUSION OF LAW The criteria for service connection for polycythemia vera are met.

Please see language below in this case the “nexus” is specifically explained as contributing to the decision to grant benefits.

“Concerning Shedden element (3), a nexus between the Veteran’s in-service herbicide exposure and his current polycythemia vera, the Board notes that there are positive nexus opinions of record. An October 2009 treatment record by Dr. Green, D.O., indicated that it was notable that the Veteran had served in Vietnam and that it was entirely possible that he had been exposed to chemicals during his tour of duty which may have contributed to his myeloproliferative disorder (polycythemia vera is categorized as a myeloproliferative disorder). Also of record are several letters from Dr. Webb, M.D., the Veteran’s primary care physician. In the most recent letter, dated August 2012, Dr. Webb noted that the Veteran was previously evaluated by a hematologist who believed that chemical exposure during the Veteran’s tour in Vietnam, specifically Agent Orange, had contributed to his current medical condition. Dr. Webb went on to reason that given the lack of other possible etiologies for his condition and the mounting evidence that Agent Orange has been implicated in other cases of polycythemia, the Veteran’s exposure would make the most sense for a cause and effect relationship. Dr. Webb opined that, based on his review of the Veteran’s records, he concurred that the Veteran’s Vietnam exposure was at least as likely as not to be contributory to his current medical condition. In the absence of any contrary nexus evidence, the Board finds the private physicians’ opinions to be the most probative evidence concerning the etiology of the Veteran’s polycythemia vera. Accordingly, the Board finds Shedden element (3) has been satisfied.”