The 2022 Tandem Meetings | Targeting chronic inflammation in MPNs
Srdan Verstovsek, MD, The University of Texas MD Anderson Cancer, Houston, TX, talks on the potential of targeting chronic inflammation in myeloproliferative neoplasms (MPNs). It is becoming increasingly evident that inflammation plays an important role in disease progression and symptom worsening through an autocrine loop where malignant cells feed their own growth through the production of anti-inflammatory cytokines. Targeting the cells affected by these cytokines could decrease fibrosis and inflammation in the bone marrow, potentially affecting the progression of the disease. This interview took place at the Transplantation & Cellular Therapy (TCT) Meetings of ASTCT™ and CIBMTR® 2022 in Salt Lake City, Utah.
Transcript (edited for clarity)
Chronic inflammation in the myeloproliferative neoplasms may be responsible for a lot of what we clinically see, particularly in the case of myelofibrosis. You have myeloproliferation, which is described in the name of the disease group, right? Myeloproliferative. “Myeloid” stands for the bone marrow cells. They grow without control, but we now know, and we have known this for a long time, but it’s coming up as a clinically relevant endpoint or a goal for inhibition, that inflammation comes with this uncontrolled growth of the cells that affects the bone marrow environment...
Chronic inflammation in the myeloproliferative neoplasms may be responsible for a lot of what we clinically see, particularly in the case of myelofibrosis. You have myeloproliferation, which is described in the name of the disease group, right? Myeloproliferative. “Myeloid” stands for the bone marrow cells. They grow without control, but we now know, and we have known this for a long time, but it’s coming up as a clinically relevant endpoint or a goal for inhibition, that inflammation comes with this uncontrolled growth of the cells that affects the bone marrow environment. It’s kind of feeding itself that you have abnormal malignant cells growing, reducing a lot of different proteins which we call cytokines, affect the stromal cells in the bone marrow that affects the growth of malignant cells, or even autocrine loop or malignant cells feeding its own growth through this potential inflammatory cytokines. We know that some of the JAK inhibitor activity, particularly on symptoms, is related to their anti-inflammatory potential. But inflammation on these cytokines lead to progressive worsening in the fibrosis in the bone marrow. And so targeting inflammation or cells that are affected by the cytokines like monocytes, like fibrocytes or fibroblasts. These are the cells in a bone marrow that are targeted for a new wave of antifibrotic medications. Through targeting those cells, you would in fact, decrease the fibrosis, decrease the inflammation in bone marrow and potentially, that’s the key here. Potentially you have a clinical benefit on improving the bone marrow function. You have improvement in anemia, thrombocytopenia, and hopefully less of a progression in the disease because you are decreasing that inflammation, decreasing the fibrosis. So we have a new chapter open here through looking really what’s happening in the bone marrow itself and how the inflammation in the bone marrow affects the progressive nature of the disease. And the questions are asked, can we alter that? And we are trying hard with antifibrotic medications in particular.
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