Radioimmunotherapy ((90) Y-Ibritumomab Tiuxetan) for Posttransplant Lymphoproliferative Disorders After Prior Exposure to Rituximab.

Posttransplantation lymphoproliferative disorders (PTLDs) are life-threatening complications after solid organ and hematopoietic stem cell transplantation. Only half of CD20-positive PTLDs respond to rituximab monotherapy, and outcomes remain poor for patients with relapsed/refractory disease, especially those who do not qualify for an anthracycline containing regimen due to frailty or comorbidities. Radioimmunotherapy (RIT) might be an option in this particular setting. We report a panel of eight patients with rituximab refractory/relapsed CD20-positive PTLDs including three ineligible for subsequent CHOP-like chemotherapy who received (90) Y-Ibritumomab tiuxetan as a single agent (n = 7) or combined to chemotherapy (n = 1). Five out of eight patients were kidney transplant recipients, while 2/8 had a liver transplant and 1/8 had a heart transplant. Patients received a median of two previous therapies. Overall response rate was 62.5%. Importantly, all responders achieved complete response. At a median follow-up of 37 months [5; 84], complete response was ongoing in four patients. Toxicity was predominantly hematological and easily manageable. No graft rejection was noticed concomitantly or following RIT administration despite immunosuppression reduction after diagnosis of PTLDs. This report emphasizes the potential efficiency of salvage RIT for early rituximab refractory PTLDs without any unexpected toxicity.

Comparisons of dosimetric approaches for fractionated radioimmunotherapy of non-Hodgkin lymphoma.

AIM: The aim of this study was to compare different dosimetric approaches on therapy naïve patients enrolled in a multicentre fractionated radioimmunotherapy trial, to determine which methodological approach correlates with bone marrow toxicity. METHODS: Twenty-height non-Hodgkin lymphoma patients were treated with one or two fractions of 90Y-Ibritumomab-Tiuxetan (11.1 MBq/kg) 8 to 12 weeks apart in four different institutions. Quantitative imaging with 111In-Ibritumomab-Tiuxetan (185 MBq) was performed at 0, 1, 4 and 7 days after infusion, starting two weeks before the therapeutic administration. A whole-body (WB) CT scan was also acquired prior to the 111In-Ibritumomab injection, for attenuation correction purposes and was segmented to derive patient-specific organ masses. All dosimetry processing was centralized in a single institution. The first method (M_2D) was based on geometric mean WB scans, corrected for attenuation, scatter and organs superposition. The second method (M_2.5D) was based on the computed assisted matrix inversion approach and used segmented CT scans. The third method (M_3D) used iterative reconstruction of tomographic scans, corrected for attenuation, scatter and collimator response. Absorbed doses were estimated for lungs, liver, kidneys and spleen using MIRD S values adjusted for organ masses. Bone marrow (BM) absorbed doses were evaluated according to imaging methods (3) and compared to blood-based approaches. RESULTS: For some patients, organ masses such as liver or spleen significantly differed from male/female reference masses, whereas lungs and kidneys masses were relatively constant. Except for lungs, absorbed doses estimated by M_2D were higher than those from M_2.5D and these, in turn, were higher that those calculated from M_3D (Wilcoxon P<8.6e-4). Median organ absorbed dose estimates were equivalent for both fractions except for the spleen. In fact, spleen absorbed doses for the second fraction were lower than those for the first fraction, regardless of the approach. Possible explanations are that patient spleen masses were kept constant for analysis of both fractions and/or that spleen uptake was lowered after the first fraction. Estimation of BM absorbed doses from blood sampling was unable to predict platelet toxicity, but image-based methods performed better. Additionally, for most organs, the absorbed dose delivered by the first fraction could predict that delivered by the second fraction. CONCLUSION: These results confirm that different acquisition/processing protocols will lead to statistically different absorbed doses. Additionally, image-based dosimetric approaches are needed in order to correlate absorbed dose to bone marrow toxicity.