A detailed overview on monitoring patients with myelofibrosis, and signs that a treatment isn’t effective.
Case: A 68-Year-Old Woman with Myelofibrosis
Abdulraheem Yacoub, MD: We’re lucky to have multiple therapeutic options for myelofibrosis, but none of them are curative and none will work in 100% of our patients. As we prescribe a new therapy and recommend this to our patients, we have to keep an eye on efficacy. Is this therapy working? [We also have to look for] adverse effects. Are the patients manifesting adverse events that might be prohibitive or need to be addressed to make the therapy more successful? This concept applies to patients with all cancers, but patients with myelofibrosis receiving JAK2 therapy have unique adverse effects that need to be tackled proactively so patients can have successful therapy.
For example, one of the early findings of favorable response to therapy is improvement in symptoms. We have standardized tools to measure symptoms prospectively, such as the MPN-SAF [Myeloproliferative Neoplasm Safety Assessment Form], which is a standard tool in the NCCN [National Comprehensive Cancer Network] Guidelines that we should apply routinely in our clinics. This is a very meaningful tool to evaluate patients having clinical benefit as they receive therapy. This is important because not every patient will benefit from therapy, and we should not continue therapy if it isn’t successful, especially if there are alternatives and other JAK inhibitors. This is something we apply routinely in our clinics to evaluate efficacy in our patients.
In addition, spleen volume reduction can be assessed clinically by splenic lengthening by examination. We implement this routinely in our clinical assessments of patients through serial physical examinations. Patients who receive new therapy with a JAK inhibitor should be assessed for splenic responses by examination. Patients might have a dramatic and early response or a slow and steady response, or they might be refractory to therapy and need to switch therapy. If we have more than 1 option, we should be very sensitive to patients who don’t respond to 1 line of therapy and switch them early to a different line of therapy without delay in their access to more successful agents. That’s how we evaluate efficacy.
In terms of adverse effects, many JAK inhibitors can cause worsening in blood counts: white blood cell count, hemoglobin, and platelets. It’s a standard of care to follow with blood tests every 2 weeks after starting therapy, especially in the first 8 weeks, to see if patients are having adverse effects that require support, like transfusion or dose reductions of JAK inhibitors. [We want] patients to continue therapy without interruption or withholding of therapy. As we start a new JAK inhibitor, we plan labs every other week, or every week if the patients have cytopenias. We plan at least monthly assessments for benefit and clinical responses, and we continue to evaluate for adverse effects of therapy going forward.
There are some unique toxicities to different agents. For example, with most JAK inhibitors, patients are at risk of infections. We like to optimize prophylaxis or vaccination prior to therapy. In the case of fedratinib, there’s a box warning for encephalopathy due to thiamine deficiency in these patients. We prefer to check the thiamine level. Some physicians also prescribe thiamine up front so that patients don’t have this complication of encephalopathy or Wernicke encephalopathy as a complication of therapy. For fedratinib and pacritinib, there’s GI [gastrointestinal] adverse effects, including nausea and diarrhea. Those are best managed by prevention rather than by allowing patients to develop toxicities and then manage them. We routinely prescribe antiemetics and antidiarrheal agents so that patients are managed proactively and they don’t have adverse effects. All those things are necessary and essential in providing successful therapy. I encourage physicians who prescribe these medications to familiarize themselves with the adverse effects and the package inserts so that they can deliver successful therapy. These are agents of great activity and great benefit to our patients. For us to use them effectively, we need to be very familiar with how to use them, the possible adverse effects, and how to mitigate this risk proactively.
Transcript edited for clarity.