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I-Tositumomab in lymphoma.

ABSTRACT: Radioimmunoconjugates are radioisotope-bound monoclonal antibodies that target radiation specifically to sites of lymphoma involvement. Initial studies of (131)I-tositumomab in non-Hodgkin lymphoma (NHL) have suggested benefit in patients with relapsed or refractory indolent disease. However, the routine adoption of this agent is tempered by concerns about associated toxicities and unclear long-term benefit. Based on a comprehensive search for studies on (131)I-tositumomab use in lymphoma, this systematic review summarizes and evaluates the evidence on the benefits and risks of this novel therapy,the predictors for response and toxicity, and the role of dosimetry and imaging studies before treatment.We identified 18 trials investigating the use of (131)I-tositumomab for the treatment of adult patients with nhl. In trials of patients with relapsed or refractory indolent nhl, overall response rates ranged from 67% to 83%. In patients with follicular nhl refractory to the monoclonal antibody rituximab, response rates remained high (65%-72%). However, in rituximab-naïve patients with relapsed or refractory indolent or transformed nhl, improvements in time to progression or survival have not been clearly established. (131)I-Tositumomab is an active agent in relapsed and refractory non-Hodgkin lymphoma that should be considered in selected patients.

SUBMITTER: Cheung MC

PROVIDER: S-EPMC2768513 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature

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I-Tositumomab in lymphoma.

Cheung M C MC Maceachern J A JA Haynes A E AE Meyer R M RM Imrie K K

Current oncology (Toronto, Ont.) 20090901 5

Radioimmunoconjugates are radioisotope-bound monoclonal antibodies that target radiation specifically to sites of lymphoma involvement. Initial studies of (131)I-tositumomab in non-Hodgkin lymphoma (NHL) have suggested benefit in patients with relapsed or refractory indolent disease. However, the routine adoption of this agent is tempered by concerns about associated toxicities and unclear long-term benefit. Based on a comprehensive search for studies on (131)I-tositumomab use in lymphoma, this ...[more]

PMID: 19862360

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Project description:UnlabelledFor optimal treatment planning in radionuclide therapy, robust tumor dose-response correlations must be established. Here, fully 3-dimensional (3D) dosimetry was performed coupling SPECT/CT at multiple time points with Monte Carlo-based voxel-by-voxel dosimetry to examine such correlations.MethodsTwenty patients undergoing (131)I-tositumomab for the treatment of refractory B-cell lymphoma volunteered for the study. Sixty tumors were imaged. Activity quantification and dosimetry were performed using previously developed 3D algorithms for SPECT reconstruction and absorbed dose estimation. Tumors were outlined on CT at multiple time points to obtain absorbed dose distributions in the presence of tumor deformation and regression. Equivalent uniform dose (EUD) was calculated to assess the biologic effects of the nonuniform absorbed dose, including the cold antibody effect. Response for correlation analysis was determined on the basis of the percentage reduction in the product of the largest perpendicular tumor diameters on CT at 2 mo. Overall response classification (as complete response, partial response, stable disease, or progressive disease) used for prediction analysis was based on criteria that included findings on PET.ResultsOf the evaluated tumor-absorbed dose summary measures (mean absorbed dose, EUD, and other measures from dose-volume histogram analysis), a statistically significant correlation with response was seen only with EUD (r = 0.36 and P = 0.006 at the individual tumor level; r = 0.46 and P = 0.048 at the patient level). The median value of mean absorbed dose for stable disease, partial response, and complete response patients was 196, 346, and 342 cGy, respectively, whereas the median value of EUD for each of these categories was 170, 363, and 406 cGy, respectively. At a threshold of 200 cGy, both mean absorbed dose and EUD had a positive predictive value for responders (partial response + complete response) of 0.875 (14/16) and a negative predictive value of 1.0 (3/3).ConclusionImproved dose-response correlations were demonstrated when EUD incorporating the cold antibody effect was used instead of the conventionally used mean tumor-absorbed dose. This work demonstrates the importance of 3D calculation and radiobiologic modeling when estimating absorbed dose for correlation with outcome.

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I-Tositumomab in lymphoma.

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I-Tositumomab in lymphoma.

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