Info from Dr. Hoffman

We met with Dr. Hoffman on Monday and gathered as much information as she had to offer about the girl who came down with lymphoma and the options for Emmett moving forward.  I know the specific details she shared won't mean much to the casual reader, but because our blog provides us with a concise, searchable medical history for future reference, I'll add most of what she shared below.

• The girl who came down with lymphoma had a different primary tumor type than Emmett (epithelioid sarcoma).  Her treatment history (and associated risk factors from her prior treatments) is still under investigation.  The drug company and the FDA want to gather and study all the available details of her medical history before determining what any impacts may be on the study moving forward.  Dr. Hoffman doesn't think this will cause the FDA to close the study, but perhaps they'll cap the total drug dose a patient can receive or limit the number of months a patient can be on the study.  But it's really too early to tell at this point.
• A secondary lymphoma is generally not a risk factor for most treatment protocols -- leukemia, on the other hand, is rather common.
• Radiation may increase the risk for a secondary lymphoma, and Dr. Hoffman believes this patient had received some radiation; however, lymphoma is still a rare side effect for irradiated patients.
• In laboratory studies, Emmett's EZH2 medicine did cause a secondary lymphoma is rats in very high dose levels (orders of magnitude higher than what humans receive).  This leads the doctors to think that this girl's lymphoma is likely caused by Emmett's medicine.
• The girl was on a lower dose (900 mg/m^2) than Emmett (1200 mg/m^2)
• She had been on the study much longer than Emmett when she came down with lymphoma -- 19 cycles is what Dr. Hoffman recalled, and each cycle is 4 weeks.  So that means she had been on the drug 76 weeks and Emmett has been on the drug ~40 weeks.
• In terms of total dose, Emmett has received ~50% of what the girl had received when she came down with lymphoma.  Perhaps this means that we have a little time before things get critical for Emmett.
• A particular patient may be genetically pre-disposed (i.e. more likely) to develop lymphoma upon exposure to a new drug than another (i.e. this girl's unique DNA may make her more susceptible to developing lymphoma than Emmett would be)
• 700 total patient have received the drug, and only 1 lymphoma case has been reported.  The 700 patients includes mostly adults -- only about 25 pediatric patients have taken the drug.  About 12-15 patients are further along on the clinical trial than Emmett is.
• Pediatrics receive a higher dose of the EZH2 medicine than adults because kids metabolize drugs differently and generally can tolerate much higher levels than adults.  Especially for kids with central nervous system tumors, you want the dose to be as high as can be tolerated to help it cross the blood brain barrier.  The adult dose is 800 mg/m^2.
• Non-Hodgkins lymphomas -- the type this drug can cause -- are generally treatable with success, though they do require a traditional chemotherapy protocol that is relatively tough on patients (and ~9 months long).  In Emmett's case, however, he's already had one of the main drugs that would be used to treat a non-Hodkins lymphoma (doxorubicin).  This drug has a total-dose cap due to potential organ damage (heart).  Dr. Hoffman was going to look into how much more doxorubicin Emmett can handle and also the treatment options for NHL without using doxorubicin (and their expected effectiveness).  We hope to hear more soon.
• The FDA and the drug company are currently agreeable to having patients (1) continue therapy at their current dose, (2) continue therapy at a reduced dose, (3) pausing therapy with the option to restart later after more information is available, (4) ceasing therapy completely (an option at any point).  These options may change at any time pending their investigations.
• If the FDA was extremely concerned, they would put an across-the-board hold on the clinical trial.  The fact that they haven't done this is good sign...for now.

After a thoughtful weekend of fasting and prayer, and after considering Dr. Hoffman's information, we decided to continue the trial at Emmett's current dose for at least two more weeks until next next MRI.  This will give the FDA/drug company (and other) doctors a chance to review all the available information and put together their recommendation.  We're also hoping to get some input from Dr. Chi in the meantime.

We know that the drug in its current form has helped Emmett significantly, and we think it's prudent to get him at least two more weeks on the medicine when weighing the risks against the benefits it's provided him.  Hopefully by the time we go back to Denver we'll have a more complete picture from the doctors that will allow us to clearly discern what our next move should be.