Rare Sarcoma With TPM3-ALK Rearrangement May Respond to Ceritinib

A case study found that a patient with an inflammatory myofibroblastic tumor and a chromoplectic TPM3-ALK rearrangement that may be involved in tumorigenesis had a strong response to the ALK inhibitor ceritinib.

A case study found that a patient with an inflammatory myofibroblastic tumor (IMT), a rare form of sarcoma, had a chromoplectic TPM3-ALK rearrangement that may be involved in tumorigenesis. The patient had a strong response to the potent ALK inhibitor ceritinib, suggesting this could be a treatment option for this malignancy.

The study was published in Annals of Oncology.

“IMTs are distinctive neoplasms composed of myofibroblasts and fibroblasts with inflammatory infiltrates including many plasma cells,” wrote study authors led by Aaron Mansfield, MD, of the Mayo Clinic in Rochester, Minnesota. IMTs can occur at any age but predominantly affect children; surgical resection is the primary therapy, though the tumors can recur, and cytotoxic therapy has not proven effective.

ALK rearrangements are found in approximately half of all IMT patients, and ROS1 and PDGFRβ occur in about one-third of patients. The authors wrote of a 32-year-old patient who presented with a metastatic IMT after progression on crizotinib followed by celecoxib.

The patient had involvement in his left lung and chest wall, his medial right thigh, and right gluteal muscle and omentum. He achieved a partial response with crizotinib, but disease progression was found 8 months later.

After 8 weeks of treatment with ceritinib, imaging studies revealed a significant partial response. He underwent surgical resection of the pulmonary lesion after 6 months of ceritinib yielded minimal residual disease burden; he then continued adjuvant ceritinib for 18 further months.

Sequencing of resected tumor tissue revealed a chromoplectic rearrangement of TPM3-ALK; this involved a complex rearrangement including a number of other known oncogenes, and was confirmed using polymerase chain reaction. In a press release, Mansfield noted that the use of the relatively new mate pair sequencing technique allowed the discovery of this specific type of mutation, and that they hope to offer the technique to other patients to help better understand mechanisms and potential treatments.

“Although it is difficult to know for certain if these chromoplectic rearrangements preceded treatment, their presence suggests that chromoplexy has a role in the oncogenesis of IMTs,” the authors wrote. “Furthermore, this patient’s remarkable response suggests that ceritinib should be considered as an option after progression on crizotinib with metastatic or unresectable IMT and ALK mutations.”