There is Hope. Part 1: Personalized Treatments for Dogs with Cancer / ImpriMed
This article was written by Mari Maeda, director of the Canine Cancer Alliance.
Personalized Treatments for Dog Cancer Patients: A New Test Might Extend the Lives of Canine Lymphoma Patients
Lymphoma is one of the most common cancers in dogs. After diagnosis, without treatment, life expectancy is short—typically 1-2 months. The most commonly used treatment for lymphoma is chemotherapy. Four chemical agents—vincristine, cyclophosphamide, doxorubicin, and prednisone—are used as the basis of the so-called CHOP (cyclophosphamide, hydroxydaunorubicin [doxorubicin], Oncovin® [a trade name of vincristine], and prednisone) protocol. Other drugs such as L-asparaginase and Tanovea might be added to the chemo regiment.
Ellie (dog in graduation cap) was diagnosed with aggressive T-cell lymphoma in spring of 2019. Here she is celebrating her 6 month remission on the therapy guided by
ImpriMed assay and doing well. Photo courtesy SVS Blue P earl
The good news is that the majority of dogs with lymphoma respond to chemotherapy with few side effects (unlike people getting chemo) and many of them will go into remission.
The bad news is that the remission is usually temporary (the average length of remission is a short 6–12 months) and there’s a big swing in variability among canine patient responses—some dogs come out of remission almost immediately, while others stay in remission for years. At this time veterinarians can’t predict what combination of drugs is best for any particular canine patient.
The good news is that the majority of dogs with lymphoma respond to chemotherapy with few side effects (unlike people getting chemo) and many of them will go into remission.
Given that cancer is unique in each dog, is there a way to select drugs in a scientific, data-driven way? Can the treatment be personalized and optimized for each dog so the treatments last and are more efficacious? And can such tests be done affordably?
A new, Palo Alto, California–based company, ImpriMed, has created a new test that analyzes live cancer cells from canine patients. ImpriMed researchers are trying to help veterinarians select the best chemotherapy drug treatments for our pups. They are running a trial now that involves hundreds of dogs at a growing number of veterinary oncology clinics in the United States.
For now, their trial is focusing on lymphoma.
I spoke with Hye-Ryeon Lee PhD, the co-founder and Chief Operating Officer of ImpriMed. Here is a summary of what I learned about their work and their service.
What does ImpriMed do? ImpriMed tests the efficacy of dozens of different drugs on the sample of live cancer cells from a canine patient. Just like with humans, different chemotherapy drugs impact different dogs in unique ways. ImpriMed can help predict drugs that work and those that don’t, so the doctor personalize treatment the treatment for pets. They are running a study with canine lymphoma patients.
How does it work? The doctor takes a small sample of a dog’s cancer cells during an appointment. This is done using a technique called Fine Needle Aspirate (FNA) to get cells from lymph nodes. The specimen is immersed in a special solution to help keep cells alive and is shipped overnight to ImpriMed’s lab in Palo Alto, CA.
What happens at their lab? Once the cells arrive, they are divided into a two-dimensional array of small "wells,"(small containment areas). Different drugs are then applied to the wells using a technology that deposits appropriate amounts of different drugs in a very precise way. Scientists then determine how sensitive the cancer cells are to each drug by waiting and measuring how many cells survive. The more cells die, the more effective the drug is for that particular dog’s cancer cells.
What drugs are tested against the cancer cells?
Drugs used in this study include small-molecule drugs approved by Food & Drug Administration (FDA) and are commonly used by veterinarians, as well as newer experimental drugs. For example, the list of drugs include: vincristine, vinblastine, lomustine, predinosone, doxorubicin, Tanovea, L-asparaginase, actinomycin D.
How long does it take to get the results back? The cancer subtyping results (e.g. B-cells vs T-cells) are returned to the veterinary clinic in a matter of days, and the drug sensitivity test results are delivered in 7-9 days. The company is working hard to reduce its turnaround time to less than a week so the vet can quickly come up with the treatment plan guided by the test result.
Figure 1: How the ImpriMed trial works
What can the vet learn from the ImpriMed ’s test result? The veterinary oncologist will get a sensitivity report of the dog’s cancer cells to different drugs, indicating 0-100% sensitivity. This report can then guide the treatment plan. For example, without the test, the vet may recommend that both canine patients Sally and Spot receive the gold standard drug combination of A+B+C+D. But the test may show that for Sally, drugs A + B are the best combination and drugs C or D has hardly any impact. Whereas for Spot, his cancer is most sensitive to drug D and F and barely sensitive to drugs A, B, and C.
What are the advantages for pet parents? This trial is an opportunity to give our pets drugs that would potentially work the best and skip treatments that are not expected to work. This also would possibly reduce treatment costs too.
Figure 2: Canine cancer treatment drugs and their effectiveness
Has the test helped extend lives of patients?
More time is needed for ImpriMed to gather proper survival data, but veterinary oncologist Dr. Kevin Choy of Seattle Veterinary Specialists (SVS) Blue Pearl in Kirkland, Washington shared the experience he had with Ellie, his 12-year old patient with lymphoma:
“I have a patient – Ellie - who was on prednisone-only hospice care, but I convinced the parents to use a traditionally less effective oral chemotherapy (Chlorambucil) for her-high grade aggressive lymphoma. It should not normally work, but as it was identified on the ImpriMed platform, we decided to give it a try especially since it‘s an inexpensive pill. While I would expect most dogs on steroid-only palliation to live 1-2 months, she is now in remission more than 6 months out."
This sounds very hopeful, but data is needed from many dogs and over a longer period of time to understand the efficacy benefits. Dr Choy says:
“Most chemotherapy protocols for [more common] B-cell lymphoma have an expected 1-year median survival rate. So I would need to see most of them going out longer than a year to make more determinations.”
We are looking forward to finding out what ImpriMed learns and concludes from all the data over time.
Are there examples of how this trial has helped canine patients?
According to Dr. Hye-Ryeon Lee :
Skye's, an eight-year old Weimaraner, lymphoma cells were tested and were shown to be very sensitive to vincristine, but not to the other drugs in the CHOP protocol. So, he was given several injections of vincristine, and the vet recommended skipping doxorubicin and prednisone, which allowed Skye to avoid exposure to extra chemo drugs. (I talked to Skye’s mom who told me that she first found out about ImpriMed through Facebook’s Fighting Canine Lymphoma support group which is a great resource for pet parents.) Sadly, Skye passed away in November, eight months after his diagnosis.
Skye was diagnosed with lymphoma in March 2019. His mom learned about ImpriMed's test and decided to use it to find best chemotherapy for his cancer.
Photo courtesy of Canine Cancer Alliance.
Hye-Ryeon Lee told me about another patient whose oncologist was considering Tanovea, but the test revealed that her cancer cells showed poor sensitivity to Tanovea which is a relatively expensive new drug on the market. So in this case, the test helped the owner and the pet parent make the decision to look elsewhere.
How can my dog get the test? You will want to visit the ImpriMed website for list of veterinary clinics currently participating in the study https://www.imprimedicine.com/.
If this website does not list a clinic close to where you live, do not worry. Email the ImpriMed team at info@imprimedicince.com to learn more and ask how your veterinarian or oncologist can arrange a test.
How much does the test cost? Because the test is now being offered as part of a clinical study and ImpriMed is still gathering data, it’s being offered free of charge. It is expected to become a paid service sometime this year.
Does ImpriMed also provide the drugs? No. ImpriMed offers a diagnostic test and is not in the business of selling chemotherapy drugs. The information they provide helps guide the veterinarians and owners to choose the treatment that’s best for their dogs.
Does the trial include immunotherapy drugs? No. ImpriMed is focused on testing small molecule chemotherapy drugs. These drug molecules directly attack the cancer cells so you can test the interaction in an ex-vivo configuration, in other words you can test cells that are outside the body. With immunotherapy, the treatment drug works with the dog’s immune system which in turn attacks cancer.
How about cancers other than lymphoma? ImpriMed is planning to start looking at other types of cancer. Stay tuned!
Is this approach going to help human cancer patients? Currently, this kind of live cell-based test is not available for human patients. But ImpriMed is definitely interested in applying what they are learning so they can help people too. The data they are collecting with dogs is anticipated to accelerate the process of getting a trial started with human patients too.
What I admire about this company is that they are serious about helping both dogs and people. Some organizations support clinical studies with canine cancer patients, with little or no interest in bringing the treatment to market for broad veterinary use. Dogs are often used as steppingstones to the much more lucrative human cancer treatment market. But ImpriMed seems to be committed to advancing research and developing their business to help both canine and human patients.
I gratefully acknowledge Amee Gilbert, Pornthira Cunningham and Nus Alom for helping to bring this article together.
Mari Maeda is the director of the Canine Cancer Alliance, a Bellevue-based nonprofit organization supporting cancer research to help pet dogs. Each year, this nonprofit hosts the Wag Love Life 5K fundraiser in September (2021). We encourage you to visit the Canine Cancer Alliance website. For additional up-to-date information follow the Canine Cancer Alliance on Facebook.
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