Combined modality ultra‐low‐dose adaptive radiotherapy and rituximab as treatment strategy for indolent non‐hodgkin lymphomas: the ut southwestern experience

Introduction: For indolent non-Hodgkin lymphomas (iNHL), ultra-low-dose radiation therapy (ULDRT) with 4 Gy (2 Gy × 2 or “boom-boom”) has demonstrated durable local control (70%), though distal relapses may occur. Concurrent systemic chemotherapy with RT extends PFS but is often avoided due to toxicity. We hypothesize that the combination of adaptive ULDRT and single-agent rituximab results in excellent local and systemic control with minimal toxicity. Methods: We conducted an IRB approved retrospective review of patients with iNHL who were treated with both ULDRT and rituximab (4 weekly doses of 375 mg/m2) as frontline therapy, either concurrently, or within a short interval (median 13 days), at our institution from 2017-2023. Treatment response and disease control (local and distant) were measured. Overall and progression-free survival (OS and PFS) were analyzed using the Kaplan-Meier method. Results: Baseline patient characteristics and treatment sites are shown in Table 1. The overall response rate at first follow up was 21/22 (95%), of which 17 sites (77%) achieved complete response (CR), 4 (18%) partial response (PR), and 1 (5%) stable disease (SD). Of those with PR, 1 had residual disease in-field, 1 out-of-field, and 2 both in- and out-of-field of RT. Repeat ULDRT was given to sites of PR with all achieving CR except for 1 patient with both in and out-of-field PR who declined salvage RT and was managed with active surveillance with SD on last follow up. Two patients experienced mild acute RT-related toxicities (diarrhea and dysgeusia), and 1 patient with Sjogren’s syndrome experienced long-term mild dry mouth. There were no major toxicities associated with rituximab. Of 14/22 initially symptomatic treatment sites, 12/14 (86%) noted resolution after treatment. In our cohort, the 2-year PFS and OS were 86% and 100%, respectively. The median time to relapse was 23 months. Of the patients who relapsed, 1 relapsed in-field, and 2 relapsed both in- and out-of-field of ULDRT. Two of these patients were retreated with ULDRT, while one is undergoing systemic treatment with bendamustine/rituximab. Conclusion: The combination of rituximab and ULDRT demonstrates sustained local and distant disease control with minimal side effects in iNHL. In situations where there is prohibitive toxicity risk for chemotherapy and/or higher radiation doses, this strategy presents a reasonable alternative. Further studies are needed to elucidate potential mechanisms of synergy and define the optimal use of this treatment paradigm. Keywords: combination therapies, indolent non-Hodgkin lymphoma, radiation therapy Conflicts of interests pertinent to the abstract G. Kaur Employment or leadership position: SANOFI, BMS, Janssen, Cellectar, Arcellx Consultant or advisory role Advisory