ADVL1522: A phase 2 study of lorvotuzumab mertansine (IMGN901) in children with relapsed or refractory wilms tumor, rhabdomyosarcoma, neuroblastoma, pleuropulmonary blastoma, malignant peripheral nerve sheath tumor, or synovial sarcoma-A Children's Oncology Group study.

BACKGROUND: Lorvotuzumab mertansine (IMGN901) is an antibody-drug conjugate linking an antimitotic agent (DM1) to an anti-CD56 antibody (lorvotuzumab). Preclinical efficacy has been noted in Wilms tumor, rhabdomyosarcoma, and neuroblastoma. Synovial sarcoma, malignant peripheral nerve sheath tumor (MPNST), and pleuropulmonary blastoma also express CD56. A phase 2 trial of lorvotuzumab mertansine was conducted to assess its efficacy, recommended phase 2 dose, and toxicities. METHODS: Eligible patients had relapsed after or progressed on standard therapy for their tumor type. Lorvotuzumab mertansine (110 mg/m2 per dose) was administered at the adult recommended phase 2 dose intravenously on days 1 and 8 of 21-day cycles. Dexamethasone premedication was used. Pharmacokinetic samples, peripheral blood CD56-positive cell counts, and tumor CD56 expression were assessed. RESULTS: Sixty-two patients enrolled. The median age was 14.3 years (range, 2.8-29.9 years); 35 were male. Diagnoses included Wilms tumor (n = 17), rhabdomyosarcoma (n = 17), neuroblastoma (n = 12), synovial sarcoma (n = 10), MPNST (n = 5), and pleuropulmonary blastoma (n = 1). Five patients experienced 9 dose-limiting toxicities: hyperglycemia (n = 1), colonic fistula (n = 1) with perforation (n = 1), nausea (n = 1) with vomiting (n = 1), increased alanine aminotransferase in cycle 1 (n = 2), and increased alanine aminotransferase in cycle 2 (n = 1) with increased aspartate aminotransferase (n = 1). Non-dose-limiting toxicities (grade 3 or higher) attributed to lorvotuzumab mertansine were rare. The median values of the maximum concentration, half-life, and area under the curve from zero to infinity for DM1 were 0.87 µg/mL, 35 hours, and 27.9 µg/mL h, respectively. Peripheral blood CD56+ leukocytes decreased by 71.9% on day 8. One patient with rhabdomyosarcoma had a partial response, and 1 patient with synovial sarcoma achieved a delayed complete response. CONCLUSIONS: Lorvotuzumab mertansine (110 mg/m2 ) is tolerated in children at the adult recommended phase 2 dose; clinical activity is limited.

Preoperative risk stratification of children with ovarian tumors.

BACKGROUND: The appropriate operative approach to pediatric patients with ovarian tumors must balance real risk of malignancy with maximal preservation of reproductive potential. We evaluate preoperative risk of malignancy in order to more precisely guide treatment, so as to err on the side of ovarian preservation if at all possible. METHODS: We retrospectively reviewed the records of all patients undergoing surgical intervention for ovarian tumors at a single institution. The primary endpoint was ovarian malignancy. RESULTS: Of 502 patients who underwent surgery for ovarian tumors, 44 (8.8%) had malignancies. Malignancy rate (95% confidence interval) was low for cystic lesions <9cm (0.0%, 0.0-2.9%) and for tumor marker-negative heterogeneous lesions <9cm (2.3%, 0.4-12.1%). High-risk profiles for malignancy included tumor marker-positive heterogeneous lesions (66.7%, 35.4-87.9%) and solid tumors ≥9cm (69.2%, 16.2-40.3%). Intermediate risk tumors included cystic tumors ≥9cm (6.8%, 3.5-20.7%), tumor marker-negative heterogeneous lesions ≥9cm (31.2%, 18.0-48.6%), and solid tumors <9cm (11.1%, 4.4-25.3%). CONCLUSIONS: We developed a decision strategy to help determine who may and may not require an ovarian-sparing approach, which warrants prospective application and validation. Ultimately, the decision to pursue an oncologic surgery with oophorectomy and staging (as opposed to fertility-preserving surgery) should be made after individualized discussion involving the surgeon, patient, and family.