This Test Might Make A Big Difference When Fighting Lymphoma

Lymphoma is one of the most common cancers in dogs. Without treatment, life expectancy is short, often only 1-2 months. The most commonly offered treatment today is chemotherapy. Multi-agent CHOP protocol, named after the acronyms of the four drugs that are combined, is often recommended. Doctors may also choose from a dozen or more drugs such as L-Asparaginase or Tanovea, depending on the patient.

Skye's mom had his cancer cells tested by ImpriMed

The good news is that the majority of dogs on CHOP protocol experience little to no side effect and respond to the treatment, going into remission.

The bad news is remission is usually temporary (median is 6-12 months) and the response in each dog varies greatly – some coming out of remission almost immediately, some remaining in remission for years. And the doctors can’t predict which combination of drugs is the best for a particular dog.

Cancer is unique in every dog. But today, most patients receive one-size-fits-all chemo treatment.

Can the treatment be made more precise and optimized for each dog?

A new Palo Alto-based company ImpriMed wants to use precision medicine to help dogs. Their new test analyzes live cancer cells from patients to help veterinarians select the best chemotherapy drugs matched to a particular dog's cancer.

For now, ImpriMed’s trial is focusing on lymphoma.

I spoke with Hye-Ryeon Lee PhD, the co-founder and COO of ImpriMed. Here is a summary of what I learned.

What does ImpriMed do?

They test the sensitivity of canine patient’s cancer cells against different drug agents. ImpriMed’s test can identify the drugs that are more effective against the particular dog's cancer cells as well as those that do not work for that patient, so the veterinarians choose the best drugs to be used to treat patients.

How does it work?

During the appointment the local veterinary doctor takes a small sample of cancer cells from lymph nodes using a technique called Fine Needle Aspirate (FNA). The specimen is stored in a special solution to keep the cells alive and is shipped to ImpriMed.

What happens at ImpriMed's lab?

There, the cancer cells are uniformly spread into a two-dimensional array of small wells. Different drugs are deposited in the wells in a very precise way.

They determine the sensitivity of cancer cells to different drugs by waiting and measuring how many cells survive. More cells die, the more effective the drug is for that particular dog’s cancer cells.

What drugs are tested against the cancer cells?

They include chemotherapeutic drugs and corticosteroids that are approved by FDA and are already in use by veterinary oncologists. They also test newer experimental drugs. The list of drugs includes, for example, 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.

Example of sensitivity test results

What information does the test result contain?

The report shows sensitivity of different drugs between 0 to 100% in predictive efficacy.

What are the benefits ?

It helps doctors and pet parents choose more efficacious drugs. It may also let dogs avoid exposure to drugs that are not expected to work and also reduce treatment costs too.

Ellie, 12 year old patient finished her chemo

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 WA 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 >6 months out ."

This sounds very hopeful and Ellie and her parents have been able to enjoy extra quality time together. To answer the question of whether the test will help extend lives, more data is needed from many more dogs and over longer period of time. 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.”

Any other patient experiences?

According to Hye-Ryeon Lee :

Skye, an eight-year old Weimaraner’s lymphoma cells were tested and was 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 avoid exposure to extra ineffective chemo drugs. (I talked to Skye’s mom who told me that she first found out about ImpriMed's test through Facebook’s Fighting Canine Lymphoma support group which is a great resource for pet parents. Skye did well for eight months but sadly he passed away in November 2019.

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.

Are there any downside to the test?

No test is ever perfect. The results may be inconclusive (not showing any drugs to be particularly sensitive or insensitive) or even wrong. But last fall, ImpriMed shared their initial sensitivity and specificity study results at the Veterinary Cancer Society meeting [Ref 1] . I have to say that being able to make treatment decisions based on some data (even if it’s not 100% perfect) is better than no data at all.

How can I request a test for my dog?

Talk to your veterinary oncologist. Or visit the company website for the current list of veterinary clinics participating in the study. If it doesn’t show anyone close by, contact them at info@imprimedicine.com and see how your local clinic can get the test ordered. They work both with regular veterinary clinics and veterinary oncologists at specialty clinics.

Does ImpriMed also provide the drugs?

No. They offer a diagnostic test and isn’t in the business of selling drugs.

Do they test immunotherapy drugs?

No. They are focused on better use of conventional chemotherapy drugs. These drug molecules directly attack the cancer cells so you can test the interaction in-vitro, ex-vivo (outside the body). With immunotherapy, the treatment drug works on the dog’s immune system which in turn attacks cancer. So creating an in-vitro test is much more challenging.

How about cancers other than lymphoma and leukemia?

They are not providing tests for other types of cancer, yet.

How about cats?

Yes, cats are eligible for this test.

Is this approach going to help human cancer patients?

Currently, this kind of live cell-based test is not available for human patients although there are some companies in developmental stages. ImpriMed is interested in applying what they are learning to help people too. The data they are collecting with dogs may acclerate getting a trial started with human patients.

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It’s going to take more time to find out if ImpriMed’s test can effectively extend lives of canine patients. What I admire about this company is

1. they are transparent and is sharing / presenting their findings

2. they are serious about both helping 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. For such companies, working with dogs is a stepping stone to a much more lucrative human cancer treatment market.

ImpriMed seems to be seriously committed to developing a business to help both canine and human patients, and to also advancing data-driven approach to canine cancer treatment.

References

[1] Lim, Sungwon, Individualizing chemotherapy for canine lymphoma based on ex vivo drug sensitivity test, Veterinary Cancer Society Meeting, Oct 17-19, Houston Texas.

I gratefully acknowledge Amee Gilbert, Pornthira Cunningham and Nus Alom valuable feedback.