Richard Joseph, MD, is an assistant professor of medicine/oncology at Mayo Clinic. His Hematology/Oncology fellowship was completed at MD Anderson Cancer Center. He is a voting member of the NCCN (National Comprehensive Cancer Network. He belongs to Melanoma International’s Scientific Advisory Board and received MIF’s Doctor of the Year award for 2015.
» BLOOD TESTS AS MARKERS OF PROGRESSION
I think my immunotherapy is working but how do I know for sure? Among blood tests doctors usually look at: – LDH? Alt? ALP? What tells us the most information.
Dr. Joseph: “At present there are no blood tests that associate with efficacy of immunotherapy in melanoma. Routine blood tests are drawn to make sure that the immunotherapy is not harming the organs such as the liver, kidney, and others. With that being said, I do find following the LDH levels to be somewhat useful when determining how a patient is doing. Specifically, I find the LDH is most helpful when the LDH is elevated to begin with and either returns to a normal level (usually good) or goes higher (usually bad). Measuring LDH levels is less helpful when it minimally changes and remains within the normal level.”
» BEST PREDICTORS
LDH is the only blood marker I know of that is most predictable, but even it can be off. I think, as a caregiver, that there is often an “unscientific” predictor of how well the person feels. Wouldn’t you think this is valid measure?
Dr. Joseph: “As mentioned above, LDH does have some clinical utility when treating some patients with melanoma. I also place a lot of weight on how a patient feels. In general, when I assess melanoma patients on therapy, I pay attention to three things: how they are feeling (most important), scans (second most important), labs (least important). Usually, how a patient is feeling is congruent with the scans and labs. There are times when a patient may feel better, but the scans are getting worse. In this case, I usually trust how the patient is feeling and decide to keep treating with the same agent, as the scans could be a sign of pseudo-progression.”
» S-100B TEST
Along with scans, does anyone routinely have the S-100B test done? That one is not showing up on my husband’s blood work, so it doesn’t look like they are following that. I have seen LDH, T3 and T4 in his labs. He is on Keytruda.
Dr. Joseph: “S-100 is a marker that is present on some, but not all, melanomas. Many attempts have been made to use S-100 in the clinic but, at present, S-100 does not have a real role in guiding clinical decision making and would be considered research. I always check patient’s thyroid function at each cycle of Keytruda and, for me, that includes a TSH and T4. Keytruda can affect the thyroid by making it not work and these labs help me decide if I need to start a patient on a thyroid supplement.”
»MEDI4736-1161 TRIAL (PDL-1) (MEK)
As for meds, I am still on the same daily course of meds for blood pressure, thyroid, kidney, and liver functions. The pharmaceutical companies, who are paying for this trial, are tracking these markers so it must have some significance. Does it?
Dr. Joseph: “While on clinical study, many labs are drawn and analyzed. Many of these labs are routine to assess the effect of the drugs on the patient’s organ system. Other labs are more for research purposes in order to give the drug company some clue of other ways the drugs might be affecting the body.”
» MARKERS FOR IMMUNE SYSTEM FUNCTION
Do markers tell you how well your immune system is running along with tumor markers like S100, CEA, Homocysteine, LDH and a total blood count? Then, if there are any irregularities, should you try to rectify them?
Dr. Joseph: “I get this question a lot from patients but, at present, there are no routine blood markers that tell you how well your immune system is working. With that being said, many groups are analyzing non-routine aspects of the blood in order to determine how the immune system might be changing while on immunotherapy. I think the ultimate goal will be to determine if we can identify patients who are more or less likely to respond to immunotherapies and, ultimately, use this knowledge to manipulate the immune system to convert non-responders to responders.
» STAGE II CIRCULATING TUMORS CELLS
Is there a way to measure circulating tumor cells ? I’ve heard that there is melanoma in the blood for all patients at all stages, but they use a different measuring methodology? Can you please clarify this?
Dr. Joseph: “Circulating tumor cells is another area of great interest for many researchers. Circulating melanoma cells can be detected in the blood through various techniques. At present, detecting circulating melanoma cells in the blood would be considered experimental. Some of the potential uses of detecting circulating melanoma cells include the following: 1) quantifying the number of cells as a means to detect early recurrence 2) determining if the number of cells associate with the efficacy of therapy 3) ability to analyze the “tumor” without performing a biopsy.”
» TYPICAL IPI RESPONSE
Are there any extra nuggets of information that I don’t know about? For example, the T cells crossing the blood-brain barrier? Unfortunately, my dad has really gone downhill. Are we having unrealistic hopes here? – Are there any reliable, specific tests/markers to indicate whether Ipi is actually working at this early stage?
Dr. Joseph: “First, let’s review how oncologists group responses for patients.
Complete Response: Total tumor burden shrinks by 100%
Partial Response: Total tumor burden shrinks by at least 30% and up to 99%.
Progressive Disease: Total tumor burden raises by at least 20% or more.
Stable Disease: Total tumor burden is +19% to -29%.
Using this strict definition, ~10% of patients achieve a partial or complete remission to ipilimumab however, an additional ~10% have some tumor shrinkage that doesn’t quite reach 30% reduction. In my experience, most patients who respond to ipilimumab do so at the first scans after receiving ipilimumab. With that being said, a minority of patients demonstrate tumor progression or stable disease. initially, before ultimately responding. This phenomenon is called pseudo-progression and occurs in ~5% of patients receiving immunotherapy. Generally speaking, patients who achieve a partial or complete response to ipilimumab have improved survival compared to those who progressive disease.”
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