Otolaryngologists See Immunotherapy as Hope for Patients with Head and Neck Cancer

by Nikki Kean •

That’s certainly the case with schwannomas and meningiomas caused by neurofibromatosis type 2 (NF2), a rare tumor suppressor syndrome, according to D. Bradley Welling, MD, PhD, who helped discover the genetic mechanisms of the rare disorder.

Dr. Welling, Walter Augustus Lecompte Professor and chair of Harvard’s department of otolaryngology–head and neck surgery in Boston, pointed to a spinal muscular atrophy type 1 (SMA1) trial that yielded “remarkable, life-altering results” (N Engl J Med. 2017;377:1713-1722).

Patients with SMA1 fail to achieve key motor milestones and often need mechanical ventilation by two years of age. The disorder is caused by a mutation in the survival motor neuron 1 (SMN1) gene, which codes for SMN, a protein necessary for motor neuron function. The rare mutation is fatal in about 90% of patients by 10 months of age, Dr. Welling noted.

In the SMA1 study, 15 patients were given a single low- or high-dose infusion of a viral vector containing DNA aimed at replacing the SMN1 gene. By the end of the study, all 15 patients were alive and event free at 20 months of age, compared with an 8% survival rate in a historical cohort, reported the investigators, from Nationwide Children’s Hospital and The Ohio State University, both in Columbus.

The most impressive results were seen in 12 patients given the high-dose regimen: 11 sat unassisted, nine rolled over, 11 fed orally and could speak, and two were able to walk independently. Dr. Welling noted that in a follow-up study of 100 infants, two infants died, and the researchers reported gains in motor function in other infants (ClinicalTrials.gov Identifier: NCT03306277).

In May 2019, the FDA approved the gene therapy (onasemnogene abeparvovec-xioi; Zolgensma, AveXis) in children with SMA.

Asked why the SMA1 study resonated so much with him, Dr. Welling replied, “It is because of the researchers’ success in transporting a gene into the central nervous system. This is exactly what we hope to achieve for our NF2 patients.”

The stakes are high for success, he stressed. “NF2 shortens the lifespan of those affected and has profound effects on quality of life, resulting in facial paralysis, hearing loss, inability to communicate, disequilibrium, and spinal cord tumors that may cause aspiration and other potentially life-threatening problems,” Dr. Welling explained. “So, it’s a very important condition for us to overcome, and certainly part of the reason why these tumors have been such a strong focus of our research through the years.”