Addition of low-dose, involved-field external beam radiotherapy just prior to radioimmunotherapy for CD20+ lymphoma: “Priming” cell death pathways?

Abstract

e18533 Background: Radioimmunotherapy is an effective and increasingly used option for patients with B-cell lymphomas. Particularly in the relapsed/refractory setting, patients may have sizable disease limited to one or a few sites. Many patients are heavily pretreated, with a subsequent downregulation of CD20 expression on the surface of lymphoma cells. Emerging evidence suggests a role for radiation to upregulate CD20 expression, which could sensitize the irradiated lymphoma cells to radioimmunotherapy. Methods: Between July 1, 2009, and December 31, 2010, we treated 13 patients with a combination of low-dose, involved-field radiotherapy (IFRT) and radioimmunotherapy (RIT) for relapsed/refractory B-cell lymphoma: 5 transformed, 4 follicular, 2 marginal zone, 1 CLL/SLL, and 1 lymphoplasmacytic. All received 4 Gy in 2 fractions IFRT to sites of active disease, 2.5 cm or larger. 131I-tositumomab was used in 8 patients and 90Y-ibritumomab tiuxetan in 5 patients. The median age of patients treated was 61 (38 – 82). The median size of persistent disease prior to treatment was 4.2 cm (2.5 – 19.5). Results: With a median follow-up of 14 months (6 – 21), 11/13 patients obtained a complete response to combined therapy and remain in remission at this time. No patients have failed within the IFRT fields. Two patients achieved a local CR but exhibited persistent disease outside the IFRT fields. All 13 patients tolerated combined IFRT and RIT very well with no toxicity from the addition of IFRT, and only transient grade 2-3 hematologic toxicity from the RIT. The progression-free survival (PFS) is 100% in patients achieving a CR and is 85% for all patients treated. Conclusions: The addition of IFRT to sites of active disease > 2.5 cm to RIT in patients with relapsed/refractory B-cell lymphomas is well-tolerated, adds no toxicity to that of RIT alone, and results in excellent PFS, particularly for patients who obtain a CR. As the only failures to therapy were outside of radiation portals, the addition of IFRT to sites of active disease may play an important role in improving PFS when added to RIT. Prospective studies are needed to further evaluate this novel combined therapeutic approach.