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Prediction of Hematologic Toxicity After Radioimmunotherapy with ¹³¹I-Labeled Anticarcinoembryonic Antigen Monoclonal Antibodies

Center for Molecular Medicine and Immunology, Garden State Cancer Center, Belleville, New Jersey

Correspondence: For correspondence or reprints contact: Malik E. Juweid, MD, Garden State Cancer Center, 520 Belleville Ave., Belleville, NJ 07109.

ABSTRACT

This study was undertakento determine the factors affecting myelotoxicity after radioimmunotherapy (RAIT) with ¹³¹I-labeled anticarcinoembryonic antigen (anti-CEA) monoclonal antibodies (MAbs). Methods:: Ninety-nine patients who received ¹³¹I-labeled MN-14 or NP-4 anti-CEA MAbs for the treatment of CEA producing cancers were assessed for platelet and white blood cell (WBC) toxicity based on the common Radiation Therapy Oncology Group (RTOG) criteria. Univariate and multivariate regression analyses were used to identify the statistically significant factors affecting toxicity among the following variables: red marrow dose, baseline platelet and WBC counts, bone or marrow (or both) metastases, prior chemo- or radiotherapy, timing of prior chemo- or radiotherapy in relation to RAIT, type and number of prior chemotherapeutic regimens, age, sex, antibody form and cancer type. Results:: Red marrow dose, baseline platelet or WBC counts and multiple bone or marrow (or both) metastases were the only significant factors affecting hematologic toxicity according to both univariate and multivariate analyses, whereas chemotherapy, 3–6 mo before RAIT, was significant according to multivariate analysis. In this retrospective study, the multivariate regression equations using these four variables provided an exact fit for postRAIT platelet toxicity grade (PltGr) and WBC toxicity grade (WBCGr) in 40% and 46%, respectively, of the 99 patients included in the analysis. Moreover, severe (grade 3 or 4) PltGr and WBCGr could be classified accurately in all cases, whereas nonsevere (grade 0, 1, or 2) PltGr and WBCGr could be classified accurately in all but 6 of 13 cases of grade 2 toxicity, in which a severe toxicity grade was estimated using the regression equations. Conclusion:: Red marrow dose, baseline blood counts, multiple bone or marrow (or both) metastases and recent chemotherapy are the most important factors related to hematologic toxicity after RAIT. This study provides a simple model for predicting myelotoxicity with reasonable accuracy in most patients. In addition, the identification of bone or marrow (or both) metastases and recent chemotherapy as significant factors for myelotoxicity may be important in the future design of clinical trials.

Key Words: radioimmunotherapy • hematologic toxicity • red marrow dosimetry • monoclonal antibodies • carcinoembryonic antigen • cancer

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