Utilizing a Personalized Diagnostic in a Class of Hodgkin Lymphoma Patients:

An Interview With Lawrence M. Weiss, MD, of Clarient Diagnostic Services, Inc.

Lawrence M. Weiss, MD

Interview with the Innovators

Lawrence M. Weiss, MD, is Medical Director of Clarient Diagnostic Services. He is Chairman Emeritus of the Department of Pathology at the City of Hope National Medical Center. He received his BS summa cum laude and his MD summa cum laude from the University of Maryland. He completed a residency in anatomic pathology at the Brigham & Women’s Hospital in Boston and a fellowship in surgical pathology at Stanford University Medical Center. He was previously an Assistant Professor at Stanford and Director of Surgical Pathology at the City of Hope. Dr Weiss’ interests lie in surgical pathology, hematopathology, and immunohistochemistry.

Clarient Diagnostic Services, Inc, a GE Healthcare Company, combines innovative diagnostic technologies with pathology expertise to assess and characterize cancer. Their stated mission is to “become the leader in cancer diagnostics by dedicating ourselves to collaborative relationships with the healthcare community to translate cancer discovery and research into better patient care.”

The rise of individualized medicine as the new direction in oncology has created the need for innovative diagnostic technologies. Clarient is meeting this need by commercializing new lab-developed tests and companion diagnostic markers for therapeutics in breast, prostate, lung, and colon cancers and leukemia/lymphoma. Most recently, they have introduced the Hodgkin Lymphoma Profile by MultiOmyx™, an aid to a pathologist’s diagnosis of CD30-positive lymphoma cases with difficult morphology or otherwise insufficient tissue to adequately evaluate the case. This test utilizes a new pathology platform that uses proprietary methodology to assess multiple proteins from a single tissue section at a single-cell level. If you have a small amount of tissue, you do not have to sacrifice or choose between important markers. You can assess them all.

We had the pleasure of meeting with Dr Lawrence Weiss in his Aliso Viejo, California, office to talk about his definition of personalized medicine, the implications of costs to a burdened healthcare system, and the venues in which MultiOmyx is best used. To view the interview in its entirety, please go to www.PersonalizedMedOnc.com/videolibrary.

PMO Thank you so much for speaking with us, Dr Weiss. As a hematopathologist, how do you define personalized medicine in oncology?

Dr Weiss Personalized medicine is different things to different people. As a hematopathologist, I think it’s matching the person’s cancer to the best diagnosis and the best treatment modalities.

PMO Personalized medicine remains sporadic and occurs mainly at well-funded academic medical centers or prompted by physicians who really understand the genetic principles behind molecular biomarkers and how to assess them appropriately. How can this situation change so that personalized medicine in oncology can be made available broadly to patients managed by the community caregivers?

Dr Weiss Clarient’s objective has always been to deliver reliable information to the community cancer caregivers, to help keep cancer care local. Bringing personalized medicine to the community and individual patients is a difficult issues – the biggest driver is cost. We’re talking about expensive diagnostic and treatment procedures. We not only have to provide innovative diagnosis and treatment, but we have to do it at a cost that is affordable to our healthcare system. Juggling the two is a difficult proposition.

PMO What are the barriers and opportunities for this to actually occur, bringing these types of molecular biomarkers and genetic principles into the community?

Dr Weiss The basic barrier is cost. The medical profession needs to convince the payers – government and private payers – that the diagnostic modalities and the treatment modalities that we want to bring to individual patients will have benefit to those patients. But just by virtue of it being individualized therapy, it may be hard to prove in clinical studies, at least in clinical studies as we provide them today. As a result, we have to invest in resources to prove to payers that our innovative therapies and treatments are going to be effective, and try to do it at a reasonable cost so that when it translates to reimbursable procedures and treatments, it’s still within the bounds of the healthcare budget.

PMO The Hodgkin Lymphoma Profile by MultiOmyx is being launched as a Clarient-validated lab-developed test which uses a new proprietary methodology to aid pathologists and oncologists in delivering a genomic profile they can use as a guide in the treatment of difficult lymphoma cases. Please explain the differentiating factors of this test as opposed to other laboratory-developed tests.

Dr Weiss When we speak of personalized medicine, we usually talk about the therapy side being personalized. But in this particular case, MultiOmyx is a personalized diagnostic. It will be utilized in lymphoma – but not every case. It will be utilized in certain types of biopsies showing particular findings as a way of making a more precise and accurate diagnosis of Hodgkin lymphoma so people can get the correct therapies that they deserve.

PMO Issues raised regarding genomic profiling include the accuracy, sensitivity, and reproducibility of results. If the right drug is to be delivered to the right patient at the right time, we have to have confidence in the results of molecular biomarker analyses. Can you please compare MultiOmyx’s tests versus genomic tests and also as opposed to proteomic tests?

Dr Weiss As of this time, genomic tests are really not helpful in the accurate diagnosis of Hodgkin lymphoma. Currently, Hodgkin lymphoma is diagnosed by having a pathologist look down a microscope, supplemented by protein studies – immunohistochemical analyses – performed in sections taken from paraffin-embedded blocks. MultiOmyx offers a superior way of looking at multiple antigens in tissue.

First, in immunohistochemistry it’s 1 antibody, 1 section; with MultiOmyx you can get numerous proteins looked at in 1 section. Therefore, if you have small biopsies, you will never run out of tissue. In fact, you’ll preserve the tissue that’s there for additional studies if they’re needed, whereas with immunohistochemistry you’re very limited.

Second, immunohistochemistry has the limitation that proteins are being examined on different tissue sections; you never quite look at the same cell. Hodg­kin lymphoma has a unique morphologic appearance in which the neoplastic element is only about 1% of the infiltrate that you see. So when you look at antibody studies you’ll see, for example, some CD30-positive cells, you’ll see some CD15-positive cells. Both are characteristics of Hodgkin lymphoma, and when you see them on the same cell it helps you toward that diagnosis.

But when you look on the typical immunohistochemistry studies, you’re never quite sure whether it’s the same cell expressing both antigens or it’s 2 separate cell populations that express those antigens.
With MultiOmyx, you can look at your CD30 or other antigen stain and see how those positive cells are stained with other markers so you have a direct comparison, whereas with immunohistochemistry there’s a little bit of guesswork in indirect comparison.

PMO Incorporating a molecular biomarker profile in the management plan for all cancer patients is an extremely expensive undertaking. How should patients be selected for biomarker analysis?

Dr Weiss There are 2 ways to select patients for biomarker analysis. First, there has to be effective therapy. If there’s no effective therapy, you can do all the analysis that you want, and it really won’t help the individual patient. There has to be something on the treatment end that one could be offered. It could be 1% of patients, it could be 70% of patients, it could be 0.1% of patients, but there has to be some benefit should a certain profile be obtained.

But I look at it another way as well. I look at it from the standpoint of whether there is something in the patient’s cancer that will benefit in diagnosis as well from a particular modality.

Hodgkin lymphoma is generally a difficult diagnosis. First of all, it’s not a very common lymphoma, and many pathologists have limited experience with the diagnosis, so that makes it hard right from the start.
Second, quite often the differential diagnosis of Hodg­kin versus something else, even benign conditions, can be quite difficult even for a very experienced hemato­pathologist. So if you have a treatment modality for those small subsets of hard cases, I think that’s personalized medicine as well.

PMO Should the Hodgkin Lymphoma Profile by MultiOmyx be added to the management plan for all patients with Hodgkin lymphoma and, if so, how can the added cost be justified?

Dr Weiss At this point in time I don’t think that MultiOmyx should be included in the diagnostic regimen for all patients with Hodgkin lymphoma. I think it should be included when the pathologist thinks there is a chance it may help the diagnosis.

So where may it help? Currently excisional biopsies represent the most common diagnostic medium because Hodgkin or any lymphoma diagnosis is a difficult one, and an important one, and you do not want to skimp on tissue. But sometimes you have to do needle biopsies; for example, a biopsy of a large mediastinal mass. Cracking the chest would be an awful lot of money as well as morbidity for the patient. If MultiOmyx can help you by more frequently obtaining diagnoses on small pieces of tissue, this actually is going to be very cost-effective.

I had a case the other day where the diagnosis in the referring pathologist’s mind, and in my mind as well, was Hodgkin versus non-Hodgkin lymphoma. We threw this on MultiOmyx and were able to get a definitive diagnosis. That’s going to save a lot of money for the system by preventing a second excisional biopsy.

Where will MultiOmyx be in the future? I think we may go away from more excisional biopsies for possible patients with lymphoma and go more to core needle biopsies to make the diagnosis, and I think MultiOmyx is going to help with that. It may be more expensive than routine immunohistochemistry, but when you factor in the cost of an excisional biopsy versus the cost of an easy outpatient needle biopsy, you may find that going the latter route is going to be the more cost-effective, and from a quality standpoint, the better way.

PMO How will MultiOmyx help cancer patients who either do not respond to therapy or acquire resistance to standard therapy?

Dr Weiss Currently for Hodgkin lymphoma, patients with favorable low-stage disease have about a 90% cure rate. For those with a higher stage or more unfavorable features, the cure rate is still relatively high, but on the order of 75% to 80%.

Typically at some point during the treatment of a patient with Hodgkin lymphoma, some radiologic studies are performed, perhaps a PET-CT scan to see if the patient is responding. In a small percentage of the cases, the patient may not respond to therapy. Is it because the patient had the correct diagnosis of Hodgkin lymphoma and is just not responding to therapy, or is there a possibility that it was an incorrect diagnosis?

Hodgkin is a tough diagnosis. We’ve made a lot of progress in terms of pathology and diagnoses, but I’d still estimate that perhaps 5% of diagnoses may be incorrect, even by expert hematopathologists who don’t always agree with each other.

So it could be that if a patient is found not to respond, or have an unusual occurrence, that this is a mandate to implement this better technology and either definitively confirm that the original diagnosis is right or that this is 1 of the 5% of cases in which you are treating the wrong disease.

PMO Education of providers, pharmacists, payers, and patients is vital in achieving personalized medicine in oncology. How is GE Healthcare positioning itself in personalizing medicine and oncology as a whole?

Dr Weiss I think GE Healthcare is very interested in personalized medicine and wants to be part of the solution. They want to bring innovative diagnostic modalities that will help guide individualized therapies.

PMO What do you foresee as the future clinical application of personalized medicine when sequencing the entire human genome will hopefully cost less than $1000 within the next several years, and how is GE Healthcare positioned for next-generation sequencing?

Dr Weiss I think there’s an unlimited potential for next-generation sequencing, particularly when the costs do come down to a reasonable point. Clarient recently acquired SeqWright Genomic Services, a DNA sequencing service organization that is well poised to be part of this revolution.

PMO What could be offered to patients without a biomarker that directs a targeted therapy, especially if this impacts a significant percentage of patients?

Dr Weiss I don’t think we ought to be giving individualized treatments without detecting the biomarkers, because we could be overtreating a segment of the population and giving them morbidity, mortality, without any benefits. I’m a big believer that for any personalized medicine therapy there ought to be a corresponding diagnostic that will give some probability whether patients will or will not respond to that therapy. I see the two as a yin-yang going together. The diagnostic has to come with the individualized therapy, otherwise it’s not individualized therapy.

PMO Do you foresee a future in which pharmaceutical and biotech companies will not develop new therapeutic agents for oncology if the agent isn’t linked to a biomarker that identifies the patient population most likely to benefit?

Dr Weiss I agree, I don’t see pharmaceutical companies or other biotech companies developing therapies without accompanying biomarkers. I think patients want it, I think payers want it, and it’ll bring cost down, and it’ll prevent morbidity in patients who don’t need that therapy. So I think the two go hand in hand, the diagnostic and the therapeutic.

PMO Thank you so much for your time and insights today.

Dr Weiss My pleasure.

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