In a major development that could open the path for more personalised and safer cancer treatments, benefiting many people in the future, medical experts in Japan have uncovered a crucial discovery that may improve the safety of cancer treatment. A study from Kyushu University, which was recently published in Leukaemia, showed that looking at cerebrospinal fluid before treatment can help predict the chance of immune effector cell-associated neurotoxicity syndrome (ICANS), a side effect that could be fatal.

Cancer immunotherapy utilises the patient's own immune system to combat cancer. One potential approach, known as CAR-T-cell therapy, involves reprogramming a patient's T cells to target and destroy cancer cells. While this therapy has been extremely effective in treating blood malignancies, it also involves significant dangers. ICANS, one of these dangers, induces inflammation of the central nervous system. In severe situations, it can cause decreased consciousness, convulsions, or even bleeding in the brain.

"ICANS can present with mild symptoms, such as headache or lethargy, but in more severe cases it can be life-threatening, with patients experiencing impaired consciousness, seizures, or brain bleeding," says Dr. Yuya Kunisaki, a professor in the Department of Clinical Chemistry and Laboratory Medicine at Kyushu University Hospital. The high incidence of ICANS after CAR-T therapy, which is around 64%, has long been a source of concern for both clinicians and patients.

The researchers collected CSF fluid from 29 patients with B-cell non-Hodgkin's lymphoma before administering CAR-T-cell treatment. Out of these, 11 patients developed ICANS and 18 did not. The scientists examined the proteins in these samples and discovered a total of 864 proteins present in all individuals. They then focused on 46 proteins with significant differences in levels between the two groups.

Finally, the researchers discovered two critical proteins: C1RL, which had higher levels in individuals with ICANS, and FUCA2, which had lower levels in these patients. By analysing the C1RL to FUCA2 ratio, the team developed a predictive test that accurately separated high-risk patients from low-risk ones. They then tested this biomarker on another group of ten patients and discovered that the ratio accurately indicated the probability of getting ICANS.

However, the research team has stated that the study's small sample size suggests that these conclusions are still preliminary. "We now need to conduct the study with a larger number of patients to fully validate our results," says Dr. Tomoko Nomiyama, co-first author and clinical technologist at Kyushu University Hospital.

In addition to early detection, the researchers anticipate that discovering these biomarkers will allow clinicians to implement preventive measures. "If the biomarker ratio shows a patient is at high risk for ICANS, we could preemptively treat them with drugs that inhibit the complement system to lower the risk," Dr. Kunisaki says. Preventive treatment could entail starting medication before CAR-T therapy begins, lowering the incidence of ICANS.

Another problem is the invasive and painful process of collecting cerebrospinal fluid. "Spinal fluid collection is an invasive and painful procedure, so most hospitals in Japan and other countries don't routinely perform it before CAR-T therapy," Dr. Nomiyama tells me. The research team is now looking into whether comparable biomarkers can be detected in blood serum, which would make the test easier and more accessible.