Dataset Information

B7H3-Directed Intraperitoneal Radioimmunotherapy With Radioiodinated Omburtamab for Desmoplastic Small Round Cell Tumor and Other Peritoneal Tumors: Results of a Phase I Study.

ABSTRACT:

Purpose

Desmoplastic small round cell tumor (DSRCT), a rare sarcoma of adolescents/young adults primarily involving the peritoneum, has a long-term survival of < 20% despite aggressive multimodality treatment. B7H3 is expressed on DSRCT cell surface, providing a target for antibody-based immunotherapy.

Patients and methods

In this phase I study, we evaluated the safety, pharmacokinetics, and biodistribution of intraperitoneal (IP) radioimmunotherapy (RIT) with the anti-B7H3 murine monoclonal antibody ¹³¹I-omburtamab in patients with DSRCT or other B7H3-expressing tumors involving the peritoneum. After thyroid blockade, patients received ¹³¹I-omburtamab as a single IP injection at escalated activities from 1.11 to 3.33/GBq/m². A prior tracer dose of IP 74 MBq¹²⁴I-omburtamab was used for radioimmuno-positron emission tomography imaging. Each injection was followed by IP saline infusion.

Results

Fifty-two patients (48, three, and one with DSRCT, peritoneal rhabdomyosarcoma, and Ewing sarcoma, respectively) received IP ¹³¹I-omburtamab administered on an outpatient basis. Maximum tolerated dose was not reached; there were no dose-limiting toxicities. Major related adverse events were transient: grade 4 neutropenia (n = 2 patients) and thrombocytopenia (n = 1), and grade 1 (10%) and grade 2 (52%) pain lasting < 2 hours related to saline infusion. Hypothyroidism was not observed, and antidrug antibody was elicited in 5%. Mean (± SD) projected peritoneal residence time was 22.4 ± 7.9 hours. Mean projected absorbed doses for ¹³¹I-omburtamab based on ¹²⁴I-omburtamab dosimetry to normal organs were low and well within tolerable limits. More than 80% ¹³¹I remained protein bound in blood 66 hours after RIT. On the basis of peritoneal dose and feasibility for outpatient administration, the recommended phase II activity was established at 2.96 GBq/m². Patients with DSRCT receiving standard whole-abdominal radiotherapy after RIT did not experience unexpected toxicity.

Conclusion

IP RIT ¹³¹I-omburtamab was well tolerated with minimal toxicities. Radiation exposure to normal organs was low, making combination therapy with other anticancer therapies feasible.

SUBMITTER: Modak S

PROVIDER: S-EPMC7768336 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundDesmoplastic small round cell tumor (DSRCT) is a rare, aggressive sarcoma. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) may improve survival.MethodsA retrospective review of anesthetic management and postoperative pain control strategies after CRS/HIPEC for DSRCT from 2013 to 2017 was performed.ResultsThe review analyzed 10 CRS/HIPEC procedures performed for nine DSRCT patients with a median age of 19 years (range 10-24 years). Six of these patients were Caucasian, and seven were men. The median operative duration was 551 min (range 510-725 min), and the median anesthesia duration was 621 min (range 480-820 min). Postoperative mechanical ventilation was necessary in 5 patients for a median duration of 1 day (range 0-2 days). The median intraoperative intravenous fluid administration was 13 ml/kg/h (range 6.3-24.4 ml/kg/h), and the colloid administration was 12 ml/kg (range 0.0-53.0 ml/kg). The median blood loss was 15 ml/kg (range 6.3-77.2 ml/kg). Nine patients received intraoperative transfusion with a median red blood cell transfusion volume of 14 ml/kg (range 10.1-58.5 ml/kg). The median intraoperative urine output was 2 ml/kg/h (range 0.09-8.40 ml/kg/h), and half of the patients received intraoperative diuretics. Cisplatin was used during HIPEC for eight surgeries. Acute kidney injury was observed in two patients, one of whom required short-term dialysis. Epidural infusions were used in eight cases for a median of 4 days (range 3-5 days). Postoperative intravenous opioid use (morphine equivalent) was 0.67 mg/kg/day (range 0.1-9.2 mg/kg/day) administered for a median of 11 days (range 2-35 days).ConclusionCytoreduction and HIPEC for DSRCT are associated with significant perioperative fluid requirements and potentially challenging pain management. Renal protective strategies should be considered for reduction of cisplatin-associated nephrotoxicity. Further investigation for a more effective, less systemically toxic HIPEC agent is warranted.