Hematopoietic trial evaluating Navtemadlin/ruxolitinib combination therapy for myelofibrosis

Myelofibrosis, a chronic leukemia, is a rare hematologic malignancy characterized by the formation of scar tissue in patients' bone marrow. The disease is a chronic form of leukemia that produces an excess of abnormal blood cells to replace normal cells, causing patients to become anemic and have an enlarged spleen.

Anemia is a disease characterized by a lack of red blood cells, which deprives tissues of oxygen, causing symptoms such as fatigue, weakness and shortness of breath. An enlarged spleen, or splenomegaly, can cause fullness or discomfort in the upper left part of the abdomen. Myelofibrosis affects the body in many ways, causing other signs and symptoms such as thrombocytopenia (lack of platelets), extramedullary hematopoiesis (abnormal growth of blood-forming cells outside the bone marrow in organs such as the spleen, liver, or lungs), and systemic symptoms experienced by most myelofibrosis patients, such as night sweats, itching, bone pain, and fever. The presence of these signs and symptoms, in turn, creates an unmet medical need in the treatment area of u200bu200bmyelofibrosis.

To address these unmet needs, researchers have initiated clinical trials designed to combat the disease and its signs and symptoms. One of these is the phase 3 POIESIS trial (NCT06479135), which is investigating navtemadlin as a Janus kinase (JAK) inhibitor ruxolitinib tablets/ruxolitinib (Ruxolitinib) as add-on therapy compared with placebo plus ruxolitinib for the treatment of patients with de novo myelofibrosis who have had an inadequate response to ruxolitinib JAK inhibitors. The POIESIS study is a randomized, double-blind, placebo-controlled, multi-center global clinical trial.

In December 2024, the latest information on navtamedlin in myelofibrosis was shared. In a previously published article,POIESIS has an innovative and unique design that is consistent with the [myelofibrosis] treatment approach adopted in routine clinical practice: additional treatment when necessary. But there are currently no approved therapies for patients who do not respond optimally to JAK inhibitor treatment.

Through the POIESIS trial, it is hoped that navtamedlin, an oral therapy under investigation, may provide additional benefits to ruxolitinib treatment compared with ruxolitinib alone. Navtemadlin targets the MDM2 protein; MDM2 reduces the activity of p53, a key tumor suppressor protein that plays an important role in the body's natural defense against cancer, making MDM2 an important target. Notably, in myelofibrosis, MDM2 levels are abnormally elevated, preventing p53 from exerting its usual anti-cancer functions.

Based on this background information, the researchers reasonably believe that becausenavtamedlin treatment inhibits MDM2, allowing p53 to kill cancer cells, it may ultimately provide a potential new treatment for patients with myelofibrosis. Patients who agree to participate in the study will receive ruxolitinib for 18 to 24 weeks at a dose determined by the study physician. If patients don't respond well to ruxolitinib, or if the treatment is not effective enough, they will enter the second phase of the study: a randomized add-on period, involving about 180 participants.

In contrast, if ruxolitinib treatment is effective in shrinking the spleen and reducing symptoms, patients can continue their current treatment but will no longer participate in the study, as described in the POIESIS trial. 4 It is important to note that if a patient fails to respond to ruxolitinib treatment at all, study physicians will work with the patient after the study is discontinued to determine their best treatment.

Overall, ruxolitinib was well tolerated. In terms of adverse events in the POIESIS trial, gastrointestinal adverse effects are possible, and prophylactic antiemetics help prevent nausea and vomiting, and antidiarrheal drugs [are important] because if we can control these gastrointestinal adverse events well, patients will tolerate the drugs better.

References:https://www.oncnursingnews.com/view/poiesis-trial-evaluates-navtemadlin-ruxolitinib-combo-in-myelofibrosis