Current Research

Under the guidance of Dr. Srdan Verstovsek, Chief of the Section of MPN, MD Anderson has become the largest center in the world for MPN patient referral and research. We see annually more than 250 new patients with MPN, far more than any other clinical center in the world, and are engaged continuously in clinical research (conduct of clinical studies) to try to find effective therapies. Over the last 6 years more than 25 clinical studies have been conducted specifically for MPN patients at MD Anderson. At the moment 8 clinical studies for MPN patients are underway. Nothing of similar proportion exists anywhere in the world.

Our work has been recognized both nationally and internationally, and Dr. Verstovsek is frequently an invited speaker at most significant hematology meetings in the world. For example, recently he has been invited to present Educational Sessions on MPN therapy at the annual American Society for Hematology meeting, American Society for Clinical Oncology meeting and European Hematology Association meeting. It is fair to say that MD Anderson has become a leader of all major new initiatives in the MPN field, and Dr. Verstovsek is Principal Investigator of a great majority of clinical studies underway for these diseases.

JAK2 Inhibitors

The development of novel therapies for patients with MPN has been historically hampered by limited understanding of the abnormal processes and molecular causes of these diseases. However, great strides have been made in this regard over the last several years. The most important recent finding in the MPN field was a discovery of a mutation in the gene called JAK2, present in 50% of ET and PMF patients, and 97% of PV patients. Mutated JAK2 gene makes abnormal JAK2 protein, which is an enzyme, and is active all the time.

It is believed that JAK2 protein is a major reason for the existence and progression of these diseases. It is highly likely, therefore, that a JAK2 inhibitor might positively affect the disease and help the MPN patients. Indeed, medications potentially able to interfere with this identified abnormality (JAK2 inhibitors) are available for clinical evaluation. Ten different JAK2 inhibitors have been so far developed for evaluation in patients with MPN, and in particular with PMF. Dr. Verstovsek was Principal Investigator for eight of them. In particular, Dr. Verstovsek is a Principal Investigator for studies that are leading to the approval of the most effective of the JAK2 inhibitors, INCB018424 (ruxolitinib). Phase I/II clinical study results have recently been published in the New England Journal of Medicine, and Dr. Verstovsek was the first author. At the moment Phase 3 approval clinical studies of this medication are underway for possible approval of it as therapy for MF and PV.

Pegasys

Separately, Dr. Verstovsek has conducted a clinical study with a medication called Pegasys, in ET and PV. Roche Laboratories developed a semi-synthetic form of long lasting IFN-α, or Pegasys, by attaching a PEG (polyethylene glycol) molecule to regular IFN-α. This significantly prolongs its presence in blood and provides extended activity over a week period of time. The drug is conveniently given at home once a week by self-injection of a pre-filled syringe. Toxicities are less pronounced and happen less often than with regular IFN-α. Patient compliance is enhanced due to convenience and better tolerance of side effects. Pegasys was evaluated in a phase II study at MD Anderson for ET and PV patients. Eighty patients participated and 80% achieved complete response, making Pegasys the best medication on the market that can be used off-label as therapy for ET and PV.

Thalidomide

Thalidomide, an agent with putative antiangiogenic (prevents new blood vessel formation) and immunomodulatory (modifies immune system) effects, has activity in PMF. Improvements in blood cell counts and reduction in splenomegaly have been reported in selected patients but at the expense of significant side effects, including sedation, neurotoxicity, and constipation. When given with prednisone (corticosteroid), these side effects are diminished and patients can tolerate a prolonged course of therapy; this translates into the improvement of blood cell counts in a significant number of patients. There is a need for more potent and less toxic analogs of thalidomide.

Revlimid is an oral thalidomide analog that has recently been approved as therapy for patients with 2 other bone marrow diseases – myelodysplastic syndrome and multiple myeloma. A clinical trial studying the efficacy and safety of Revlimid and prednisone in PMF has been recently conducted at MD Anderson by Dr. Verstovsek and proved to be effective therapy in 35% of patients, again making this combination the best therapy that can be prescribed at the moment to patients with PMF with medications that are approved for different bone marrow diseases (off label use).