A promising experimental method for treating ad­vanced leukemia may point the way to important new treat­ment options for multiple myeloma.

“It is very exciting,” said Dr. Leif Bergsagel, a myeloma specialist from the Mayo Clinic in Arizona who was not involved in the study investigating the leukemia treat­ment. “I think this ap­proach could and should be extended to multiple myeloma.”  He pointed out, however, that “It will be several years before myeloma patients will be treated this way.”

In two recently published research articles, scientists from the University of Pennsylvania described initial results of a pilot study they are conducting.  The results are for three men with very ad­vanced cases of chronic lym­pho­cytic leukemia (CLL).  Each of the men in the study received an experimental treat­ment that used genetically altered versions of the patient's own immune cells to attack the patient's cancer cells.

Two of the men in the study achieved com­plete responses and continue to be free of any signs of cancer after 10 months of follow-up time. The other patient achieved a partial response lasting at least eight months.

The Penn researchers said that they plan to treat more patients with longer follow-up times and that they would like to expand their study to include other types of cancer.

As with myeloma, donor stem cell trans­plan­ta­tion is cur­rently the only possible cure for CLL. However, most CLL patients who receive a trans­plant relapse, and there are sig­nif­i­cant risks and side effects to trans­plan­ta­tion.

The study authors suggested that their new ap­proach has the poten­tial to cure leukemia patients like donor stem cell trans­plan­ta­tion, but in a safer manner.

Previous studies, including those for myeloma, have attempted to use patients’ immune cells to kill their cancer cells. However, these studies have had limited success. According to Dr. Bergsagel, the Penn ap­proach to modifying the patients’ immune cells “is quite different from anything tried before for multiple myeloma.”

In the Penn study, the researchers collected T-cells, which are a type of white blood cell, from the patients in the study.

The T-cells were then infected with a virus designed to genetically alter the T-cells so that they can recognize, attack, and kill leukemia cells.

The virus also was structured so that the altered T-cells would be able to reproduce and pass along to their later generations the ability to recognize and kill leukemia cells.

Once the patients in the study had their T-cells collected and altered, the patients were treated with chemotherapy, and the engi­neered T-cells were then re-infused into the patients.

Within a couple weeks of treat­ment, each of the patients developed flu-like symp­toms due to tumor lysis syn­drome, a life-threatening com­pli­ca­tion caused by large numbers of cancer cells dying too fast for the body to be able to dispose of them. Within a couple more weeks, the patients recovered from the con­di­tion and, in two of the three cases, no leukemia was able to be detected.

The Penn researchers found that, as designed, the T-cells infused into the study patients multiplied dramatically. Additionally, six months after treat­ment, the patients still had T-cells that persisted in seeking out and killing leukemia cells.

Leukemia cells are malignant forms of immune cells known as B-cells. The modified T-cells in the Penn study were not able to dif­fer­en­ti­ate between leukemia cells and healthy B-cells. As a result, the patients in the study also ex­peri­enced loss of normal B-cells and required monthly intravenous doses of immuno­glob­u­lins to prevent in­fec­tion. The study researchers note, though, that there are methods to counteract overactive T-cells, including immunosuppressive agents.

An ap­proach similar to the Penn method could be used to treat multiple myeloma, although it would need to be modified so that the T-cells target myeloma cells.

Multiple myeloma cells are cancerous forms of plasma cells, another type of immune cell. It is therefore possible, Dr. Bergsagel explained, that “If [the Penn ap­proach] is successful in myeloma, it might perma­nently wipe out all plasma cells, both normal and malignant.” He added, however, that it is possible for people to live without plasma cells.

Dr. Bergsagel also cautioned that genetically engi­neer­ing T-cells could activate cancer-causing genes, or inactivate genes that suppress cancer, eventually leading to T-cell leukemia.

“Only with the more widespread clin­i­cal use of [engineered] T-cells will we learn whether the results…reflect an authentic ad­vance to­ward a clin­i­cally applicable and effective ther­apy or yet another promising lead that runs into a barrier that cannot be easily overcome,” wrote Drs. Walter Urba and Dan Longo from the Chiles Research Institute in Portland, Oregon, in an editorial about the Penn study.

For more in­­for­ma­tion about the experimental leukemia treat­ment, see the study results in The New England Journal of Medicine ^[1] and Science Translational Medicine ^[2] as well as the related New England Journal of Medicine editorial ^[3].