Researchers recommend new standard of care for families with hereditary neuroblastoma linked to ALK mutation

Researchers at Children’s Hospital of Philadelphia (CHOP) highlighted the success of anaplastic lymphoma kinase (ALK) inhibition therapy in treating hereditary neuroblastoma, a rare subset of a common childhood cancer. Researchers suggest that the findings, published recently in JCO Precision Oncology, could help establish a new standard of care.

Despite significant advances in the treatment of high-risk neuroblastoma, the 5-year survival rate after diagnosis remains less than 50%. However, Yael P. Mossé, MD, a senior study author and a Professor of Pediatrics in CHOP’s Cancer Center, and her team have previously found that most familial cases are linked to the ALK mutation, which can be tested for and directly targeted.

In this case report, Mossé focused on a mother and daughter who were both diagnosed with neuroblastoma and carried the ALK R1275Q mutation, demonstrating how they achieved long-term remission with targeted ALK inhibitors.

“Our research marks a major advancement in precision medicine for patients predisposed to hereditary neuroblastoma,” said Mossé. “With these findings, we can offer new hope for affected families and pave the way for more personalized, less invasive treatment strategies in pediatric oncology.”

In the study, researchers demonstrated that small molecule ALK inhibitors, initially developed for sporadic neuroblastoma with non-inherited ALK mutations, could be even more effectively implemented for hereditary cases. The daughter was diagnosed with neuroblastoma at six months old and following standard chemotherapy and surgery that failed her, she responded dramatically to the ALK inhibitor, crizotinib, after her cancer recurred.

The mother, who had been asymptomatic, was diagnosed at 36 years old with bilateral adrenal tumors during a pregnancy five years later. After delivering a healthy baby, she began crizotinib, later switching to a different ALK inhibitor, alectinib, due to side effects. Following surgical removal of the tumors, the mother continued alectinib treatment and has maintained remission for several years. Both the mother and daughter undergo semiannual surveillance with whole-body MRI and circulating tumor DNA (ctDNA) testing with no evidence of disease recurrence.

The authors say the report could change how hereditary neuroblastoma for patients with an ALK mutation is treated and followed. They recommend ALK inhibitors as a frontline therapy for patients with the inherited mutations, potentially reducing the need for intensive chemotherapy and surgery. They also stress the importance of lifelong monitoring, challenging current guidelines that end surveillance in childhood. Next, the researchers plan to study whether people with hereditary ALK have a lower risk of developing drug resistance than those with non-inherited mutations.

Researchers at Children’s Hospital of Philadelphia (CHOP) highlighted the success of anaplastic lymphoma kinase (ALK) inhibition therapy in treating hereditary neuroblastoma, a rare subset of a common childhood cancer. Researchers suggest that the findings, published recently in JCO Precision Oncology, could help establish a new standard of care.

Despite significant advances in the treatment of high-risk neuroblastoma, the 5-year survival rate after diagnosis remains less than 50%. However, Yael P. Mossé, MD, a senior study author and a Professor of Pediatrics in CHOP’s Cancer Center, and her team have previously found that most familial cases are linked to the ALK mutation, which can be tested for and directly targeted.

In this case report, Mossé focused on a mother and daughter who were both diagnosed with neuroblastoma and carried the ALK R1275Q mutation, demonstrating how they achieved long-term remission with targeted ALK inhibitors.

“Our research marks a major advancement in precision medicine for patients predisposed to hereditary neuroblastoma,” said Mossé. “With these findings, we can offer new hope for affected families and pave the way for more personalized, less invasive treatment strategies in pediatric oncology.”

In the study, researchers demonstrated that small molecule ALK inhibitors, initially developed for sporadic neuroblastoma with non-inherited ALK mutations, could be even more effectively implemented for hereditary cases. The daughter was diagnosed with neuroblastoma at six months old and following standard chemotherapy and surgery that failed her, she responded dramatically to the ALK inhibitor, crizotinib, after her cancer recurred.

The mother, who had been asymptomatic, was diagnosed at 36 years old with bilateral adrenal tumors during a pregnancy five years later. After delivering a healthy baby, she began crizotinib, later switching to a different ALK inhibitor, alectinib, due to side effects. Following surgical removal of the tumors, the mother continued alectinib treatment and has maintained remission for several years. Both the mother and daughter undergo semiannual surveillance with whole-body MRI and circulating tumor DNA (ctDNA) testing with no evidence of disease recurrence.

The authors say the report could change how hereditary neuroblastoma for patients with an ALK mutation is treated and followed. They recommend ALK inhibitors as a frontline therapy for patients with the inherited mutations, potentially reducing the need for intensive chemotherapy and surgery. They also stress the importance of lifelong monitoring, challenging current guidelines that end surveillance in childhood. Next, the researchers plan to study whether people with hereditary ALK have a lower risk of developing drug resistance than those with non-inherited mutations.