The Power of the Immune System: New Treatment for Painful Blood Cancer Side Effect

CURE, Hematology Special Issue (October) 2021, Volume 1, Issue 1

A new T-cell therapy can be highly effective in treating BKV-associated hemorrhagic cystitis while minimizing side effects.

Using BK virus (BKV)-specific T cells from healthy donors to treat BKV-associated hemorrhagic cystitis, a painful side effect associated with immunosuppression from stem cell transplants, may relieve the complication faster in patients with lymphoma or leukemia, according to trial results.

“What was very important was that within a week of giving the cells, the majority of patients’ symptoms improved,” Dr. Katy Rezvani, professor of stem cell transplantation and cellular therapy at The University of Texas MD Anderson Cancer Center in Houston and lead study author, said in an interview with CURE®. “The effect of the cells is relatively rapid.”

BKV-associated hemorrhagic cystitis occurs more frequently in patients with leukemia or lymphoma who received a treatment of allogeneic stem cell transplantation. As a result, it can lead to patients having blood in their urine and passing clots, which can cause urinary retention (difficulty urinating or completely emptying the bladder) and, in more severe cases, kidney disease.

In patients who receive stem cell transplants, those who have a half match (when patients only have some genetic similarities with the donor’s immune system) are at an increased risk for BKV-associated hemorrhagic cystitis because they are more immunosuppressed. Approximately 40% of patients who have a half match develop this complication.

In the phase 2 trial, BKV-specific T cells, which recognize and attack BKV, from healthy donors were given once intravenously, with the option to receive additional doses every two weeks if needed. Of the 59 patients enrolled in the trial, 67.7% had complete (all symptoms resolved) or partial (almost all symptoms resolved) responses within 14 days. This increased to 81.6% after 28 days.

Some intolerance was observed in patients who were previously treated with steroids, which can kill T cells. There were no side effects, and there were no reports of new liver or gastrointestinal graft-versus-host disease (GVHD, occurs when the donor's cells attack the patient's cells) associated with the antiviral T cells, aside from a few cases of skin GVHD that quickly resolved with corticosteroids.

This treatment has the potential to stop the vicious cycle that comes with the current standard of care, which consists of hospitalization with continuous bladder irrigation (using a catheter to wash out the bladder) and morphine infusion to help patients tolerate the pain, according to Rezvani.

“This outpatient treatment is preventing patients from having to be admitted (to the hospital), which is wonderful because patients come into hospital with one thing, they stay in the hospital for a few weeks, then they develop other complications,” Rezvani explained. “They start getting other infections, they get pneumonia, they become malnourished, etc.”

According to Rezvani, one donor can produce up to 50 doses of T cells, which are frozen until needed. “Every time the patient comes (into the hospital), within 24 hours we can treat them,” she said.

Of note, the therapy is only available at MD Anderson, so patients with the complication would need to travel to the health center to receive it — an option that may not be possible because of physical condition or finances. “I’m hoping that we will get to a situation where we’ll be able to start a multicenter study at some point,” Rezvani said, which would make the care more accessible to patients. “In the meantime, I think the greatest limitation really is that patients will have to come to MD Anderson to receive the treatment, and for many patients with the terrible BKV hemorrhagic cystitis, this is not obviously possible.”

Until then, Rezvani is focusing on the next generation of the treatment: genetically modifying BKV-specific T cells that are more resistant to steroids, thus broadening the patient spectrum that the treatment could help.

“It’s important to realize that the use of immunotherapy against viruses and cancers (has) opened up a very exciting new era of treatment for our patients,” she concluded. “We are learning a lot more from the immune system (and are harnessing) the power of the immune system to fight infections and cancers. ... I think the field is going to continue to grow, and many more such treatments to target both viruses and cancers (are) going to become available.”

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