For medical oncologists, the choice of chemotherapy drugs is one of statistical probability.
For cancer patients, it is a matter of life and death.
The problem is that cancer patients are not statistics and each patient responds quite uniquely.
A drug with no activity in one patient may be brilliantly effective in the next. Could a drug that was used previously numerous times and shown to fail have resurgence of activity in a patient?
Hairy Cell Leukemia Patient Finds Us
A 57-year-old gentleman visited my office in July of 2014 with his step mother, who had advanced pancreatic cancer. Unfortunately, her condition worsened and she was unable to receive treatment. The same fellow returned several months later.
He felt so convinced of the merit of our assay-directed approach that he wanted to offer his assistance in “getting the word out”. He explained that he himself had hairy cell leukemia for the past 15 years and had become resistant to virtually all therapies. He was quite upfront when he suggested that his motivation to help us was in part the hope that we might be able to help him in the future if he ever needed treatment again.
My History With This Rare Disease
This was ironic in that hairy cell leukemia was a rare disease that I knew well.
In January of 1985, while a fellow at Scripps Clinic in La Jolla, California, I conducted the original laboratory experiments that tested 2-CdA against hairy cell leukemia, showing for the first time that this drug was highly active in this disease. Five years later, clinical trials confirmed the finding which led to its worldwide adoption as the gold-standard for hairy cell leukemia treatment.
At first, the patient remained well. Then in October of 2015, his disease took a turn for the worse. As I became more engaged in his case I realized that he had been treated repeatedly with 2-CdA and with just about everything else including a clinical trial testing the newest targeted agent for B-Raf mutations, Vemurafenib.
Though initially effective, Vemurafenib had caused significant toxicities. Now a year off active treatment he was rapidly progressing. Blood transfusions became frequent as his white count and platelet count fell to dangerous levels. It appeared our assistance would be necessary after all.
A bone marrow was performed and the aspiration revealed a “dry tap” indicating 95% replacement by hairy cells. More worrisome was the fibrosis associated with aggressive disease. A small portion of the marrow was submitted to our laboratory.
Functional Profiling Test Results
We examined a wide array of drugs via our EVA-PCD functional profile. Among the findings was resistance to Vemurafenib, despite his gene profile identifying a B-Raf mutation.
More interesting was the resurgence of sensitivity to 2-CdA, a drug that he had received and failed many times before.
Would it be possible to go back to a drug that he had unequivocally failed, a drug that most physicians would not give due to prior resistance?
Despite his history and conventional wisdom, I felt convinced that the patient would benefit from 2-CdA based therapy due to the sensitivity identified in the laboratory. We were intrigued by the combination of 2-CdA with the antibody Rituximab.
Borrowing from small clinical trials, we recommended that combination.
The patient suffered toxicities. His blood counts fell and he developed two serious infections. After hospitalization, an attempt to administer a second dose of Rituximab was cut short by his unusually severe allergic reaction.
As we pondered how to continue, with only 5 days of 2-CdA and one dose of Rituximab under our belts, we noticed that the platelet count, hemoglobin and white count had returned to normal.
Was it possible that the patient had responded to 2-CdA and a single dose of Rituximab? While many would have discarded 2-CdA-based therapy which he had failed so many times before, we wondered whether our assay-directed choice might have been just right.
Results Were Surprising
The only way to confirm our finding was to conduct a bone marrow biopsy. Unlike the first “dry tap,” this marrow flowed freely.
I received a sample expecting to conduct further laboratory studies for later drug selection, but could not identify a single hairy cell. Not one!
At first, I attributed this to sampling error and waited for the bone marrow biopsy report. The results were astonishing. Where the prior bone marrow had been 95% hairy cells just two months earlier, this marrow had 0.02% hairy cells and far less fibrosis. He was in a near complete remission, all with a drug that few would have chosen.
We delight in his good outcome and feel vindicated in the use of the right drugs for the right patient.
The Power of Functional Profiling
Most physicians would not have returned to 2-CdA which the patient had previously failed.
Most physicians would look to the next experimental agent.
Yet we achieved the desired end with a drug that most would not know to use. Why? Because we knew that in this particular patient, regardless of his hairy cell leukemia treatment history and prior exposures, he was sensitive.
This is emblematic of the approach we must adopt if we are to achieve the lofty goals of precision medicine.
Precision medicine, after all, is not a technology; it is a medical discipline that uses available resources to match patients to therapies. While genomic and proteomic approaches have been unable to meet these needs, functional approaches continue to provide patients with actionable findings and superior outcomes.
As the patient subsequently stated, he intends to “put his marrow where his mouth is” as he sets out to spread the word about successfully matching patients to therapies using functional profiling.
I welcome your thoughts and comments.
Dr. Robert Nagourney, has been internationally recognized as a pioneer in cancer research and personalized cancer treatment for over 20 years. He is a TEDX SPEAKER, author of the book OUTLIVING CANCER, a practicing oncologist and triple board certified in Internal Medicine, Medical Oncology and Hematology helping cancer patients from around the world at his Nagourney Cancer Institute in Long Beach, California. For more info go to NAGOURNEYCANCERINSTITUTE.COM