Fred Hutch at ASCO

A first-of-its-kind leukemia immunotherapy with CAR-T cells

On Monday, Dr. Cameron Turtle will present data from an ongoing, early-stage clinical trial indicating that a first-of-its-kind immunotherapy is safe and feasible in certain patients with particular forms of acute lymphoblastic leukemia, non-Hodgkin lymphoma and chronic lymphocytic leukemia. This therapy involves engineering immune cells called T cells with a molecule known as a chimeric antigen receptor, or CAR, that empowers the T cells to recognize and eliminate the patient’s cancer. CAR T-cell therapy has been gaining attention for the encouraging results it has generated, but aspects of the approach still need to be refined to make it as safe and effective as scientists believe it can ultimately be.

To that end, Turtle, Dr. David Maloney, and their Hutch colleagues are testing a unique form of the therapy. They are engineering two very specific subtypes of T cells with a CAR that targets certain B-cell cancers, and they are giving those engineered cells to patients in a specific ratio, like a pair of carefully measured recipe ingredients. This is the first trial ever to test CAR T cells given in a defined combination to try and produce a more consistent form of the therapy.

At ASCO, Turtle will discuss results from more than 50 of the first patients treated on the trial, a majority of whom received the precisely balanced cocktail of therapeutic T cells. So far, the results show the cancer was eliminated from the bone marrow in most of the ALL patients and was completely or partially eliminated in approximately two-thirds of the NHL and CLL patients. The team is now using the defined-composition CAR T-cell cocktail to work out what factors are important in determining outcomes in patients who receive T-cell therapy for cancer.

Red wine linked to improved colorectal cancer prognosis

New findings by Dr. Amanda Phipps of the Public Health Sciences Division regarding alcohol and colorectal cancer prognosis will be presented on Saturday.

Evaluating data from a phase 3 randomized drug trial in 1,984 patients with stage 3 colorectal cancer, Phipps and her colleagues found that patients who reported drinking red wine regularly prior to their cancer diagnosis had about a 20 percent better survival than those who didn’t report red wine consumption. Red wine drinkers had a significantly longer average time from diagnosis to cancer recurrence or death as compared to those who didn’t imbibe.

The researchers also found a similar association between drinking white wine and favorable colon cancer outcomes, but since very few patients reported being regular, frequent consumers of white wine, the findings were intriguing but inconclusive, Phipps said. The study found no association between beer or liquor consumption and better colorectal cancer prognosis.

“The fact that we found an association with lifetime patterns of wine consumption, but not with recent patterns of beer or liquor consumption, could tell us something about the mechanism by which alcohol impacts colon cancer,” Phipps said. Since prior studies have suggested that drinking red wine is beneficial for heart health, it is possible that the mechanisms responsible for the cardiovascular benefits of red wine may also have an impact on colon cancer progression, she said. “It is also possible, however, that those patients who report drinking red wine on a regular basis are different than other patients in additional ways that could have impacted their colon cancer outcomes and general heath, such as diet.”

Improving the value of prostate cancer screening

Finding prostate cancer by prostate-specific antigen, or PSA, screening is drawing scrutiny due to the tricky balance between the benefits of early detection and risks of overdiagnosis and overtreatment. To smooth out those tradeoffs, epidemiologists and guideline groups have suggested more individualized and more conservative monitoring methods.

Now, Fred Hutch public health researcher Dr. Joshua Roth and colleagues have assessed the value of such “smarter” screening strategies, as well as the impacts of increased use of active surveillance among men with low-risk disease found by screening. Roth will present the findings at ASCO on Monday.

Roth and colleagues in the Hutchinson Institute for Cancer Outcomes Research, or HICOR, conclude that personalized PSA-screening strategies rooted in a higher PSA biopsy threshold (meaning the PSA level has to be over a certain threshold before a follow-up biopsy is ordered) have the potential to be cost-effective compared to no screening — especially when combined with “active surveillance” for low-risk cases.

Under active surveillance, men are more stringently monitored, often through an annual battery of PSA tests, digital-rectal exams and biopsies.

Roth and team — including Fred Hutch biostatistician Dr. Ruth Etzioni — extended an established model to project life years, quality-adjusted life years, and the costs for cohorts of U.S. men from age 40 to death who underwent among 15 different screening strategies. They then evaluated the cost effectiveness of each strategy compared to no screening in terms of cost per life year and cost per quality-adjusted life year.

“Prostate cancer screening has been shown to catch a lot of prostate cancers early, but then, for many of those men, it’s probably most appropriate for them to just be monitored to see if their disease progresses,” he said.

In most men, prostate cancer is slow-moving and not lethal. Still, some opt for surgery or radiation therapy. Both can carry serious side effects. And a number of those patients, Roth said, may not derive worthwhile benefits – either for their long-term health or their wallets.

The study found that all PSA-screening strategies are expected to increase life years versus no screening, and were highly cost-effective: $3,500 to $15,000 per life year gained. To pinpoint an acceptable cost range, Roth and colleagues picked an upper payment threshold of $150,000 per quality-adjusted life year, meaning that paying anything less would be considered “cost- effective.”

When health-related quality of life was used to measure effectiveness, only PSA-screening strategies with high PSA biopsy thresholds were found to be cost-effective: $45,000 to $150,000 per quality-adjusted life year gained, the researchers wrote. 

Costs related to bone-related complications in patients with metastatic prostate cancer

Dr. Jean McDougall of the Public Health Sciences Division will share, via a Monday poster session, new findings regarding costs and resource utilization associated with skeletal events, or complications, in patients with prostate cancer that has spread to the bones. For the study, skeletal events were defined as fracture, spinal-cord compression or the need for surgery or radiotherapy to the bone.

McDougall and her colleagues at the Hutch and University of Washington conducted the study to understand the potential value of recently approved drugs for prostate cancer that may delay or prevent skeletal-related events, or SREs.

The study analyzed data from 891 men aged 65 and older who had been diagnosed with prostate cancer and bone metastases and compared them to a similar group of patients with advanced prostate cancer who had not suffered skeletal complications.

The researchers found that medical costs to patients with SREs were more than $21,000 higher than costs to patients without skeletal events, and those costs continued to increase in proportion with the number of SREs.

Resource use was also substantially higher in patients who suffered skeletal-related events. Those with one or more SRE had twice as many emergency room visits and nearly four times as many hospitalizations as compared to those who did not.