JNJ-64619178 for Myelodysplastic Syndromes

The most common side effects were fever and pain in the arm or back. The most frequent side effects were back pain, muscle pain, fever, and arthralgia. For some side effects, the highest rates were seen in patients receiving the 2 mg JND-64619178 dose as opposed to the 0.5, 1.0, or 1.5 mg dose.

The treatments listed above do not cure myelodysplastic syndromes but can reduce their symptoms and reduce the number of blood transfusions needed. The benefits on survival from these agents should be carefully balanced with their side effects, patient resistance and the financial cost of these agents. For MDS patients eligible for HSCT, consideration must be given to choosing between the benefit of HSCT versus the risks of chemotherapy for both the patients and the donor. An individualized plan must be discussed and carefully weighed.

The treatment of myelodysplastic syndromes includes various medications in addition to supportive care. The most common is the antiproliferative agent thalidomide and protease inhibitor. Immunosuppressants, such as thymoglobulin, can be employed in patients who do not respond to other medication, but immunosuppressive agents are associated with high morbidity.

Myelodysplastic syndromes are a diverse group of neoplastic disorders, all characterized by abnormal production of red blood cells, white blood cells and/or platelets by normal hematopoietic cells. However, the etiopathology and genetic predisposition to myelodysplastic syndromes are distinct between cases.

As many as 100,000 people per year in the United States can be diagnosed with a MDS. Approximately 40,000 of these patients have a myelodysplastic crisis, which implies that myelodysplastic syndrome patients in the United States suffer one-third of all myelodysplastic crises described in the current literature.

Patients who present with symptoms of MDS generally do not have conclusive criteria to support the diagnosis of MDS. The diagnosis of MDS is bolstered by finding cytopenias, marrow blast ≥ 10%, and pancytopenias by ≥ 8% on peripheral smear examination. The finding of dysplastic megakaryocytes on a bone-marrow aspirate (BMAs) confirms the diagnosis of MDS. The BMAs may be normal (5%), minimal changes defects (6%), dysplastic megakaryocytes (36%), and dysplastic megakaryocytes with ring-out (20%), similar to what is seen in MDS with ring-out.

Both a genetic mutation and environmental factors are involved in the development of MDS. There is a significant risk of MDS in solid-organ transplant recipients. There is also a significant risk of acute myeloid leukemia in non-Hodgkin's lymphoma survivors. There has not been a consistent genetic signature for MDS and AML, but recent studies have identified risk loci consistent with previous linkage and association studies. MDS may have a common genetic abnormality, a chromosomal abnormality, or both. It is estimated that 10% of MDS patients will eventually require allogeneic hematopoietic stem cell transplantation (HSCT), with the likelihood increasing with older age and blast transfusion at diagnosis.

JUBIO is currently undertaking a Phase III trial in the USA to evaluate the safety and efficacy of low-dose JUBIO plus bendamustine in relapsed or refractory chronic myeloid leukemia that has received two prior generations of therapy. This trial is scheduled to start in early 2017 and is expected to be completed in 2 yr.

As we progress into understanding the pathogenesis of myelodysplastic syndrome, researchers are beginning to explore possible targets in the NF-κB pathway to stop the disease. However, until now, no effective therapy has been discovered that can modify the NF-κB pathway to control the disease progression. By looking at the effects of NF-κB pathway inhibitors on myelodysplastic syndromes, we hope to find an avenue to treat these disorders.

Despite advances in understanding of the pathophysiology and biology of MDS, we have a significant lack of effective treatments. A more detailed understanding of the molecular mechanisms underlying the pathophysiology of MDS may allow the identification of specific molecular therapeutic targets that may be of therapeutic value and might assist in the optimization protocols of existing MDS-associated therapeutic regimes.

Patients with low or intermediate risk, newly diagnosed MDS should consider clinical trial enrollment. Patients with an advanced-stage disease or with a dismal prognosis who wish to stay well for longer on less efficacious treatment should consider clinical trial enrollment as well. These patients may benefit from a trial and can achieve a higher OS over time.