Indolent lymphomas

At the 18th ICML held in Lugano, several notable updates were presented regarding the management of indolent lymphomas. Dr Fulvio Massaro, a hematologist from the Jules Bordet Institute in Brussels, highlighted two key areas of progress: the renewed interest in low-dose radiotherapy and the increasing adoption of chemo-free regimens in frontline treatment. Both developments reflect a broader trend toward treatment strategies that aim to reduce toxicity while preserving efficacy in indolent lymphomas.

The first abstract, presented by colleagues from MSKCC focused on the role of low-dose radiotherapy in patients with indolent lymphomas. This retrospective analysis included over 280 patients diagnosed with either follicular lymphoma or marginal zone lymphoma, roughly evenly distributed between the two subtypes. All patients were treated with curative intent using low-dose radiotherapy, delivered either in a single session or across two consecutive days. The study reported a 5-year PFS of 64%, with a particularly low incidence of radiation site failure (15% at five years). Notably, only 6% of patients required additional radiotherapy at the early response assessment conducted six months post-treatment. These encouraging results have prompted the design of a forthcoming phase 3 trial that will compare very low-dose radiotherapy against conventional dose schedules to formally assess non-inferiority in terms of disease control and toxicity.

The second abstract, presented by Paolo Strati and colleagues from MD Anderson Cancer Center described a phase 2 trial investigating a fully chemo-free regimen in the frontline setting for indolent lymphomas. The study enrolled 60 patients, comprising 50 with follicular lymphoma and 10 with marginal zone lymphoma. The treatment protocol combined acalabrutinib with rituximab and lenalidomide. Initially, patients received 12 cycles of rituximab and lenalidomide alongside 13 cycles of acalabrutinib. In a subsequent study amendment, the regimen was shortened to six cycles of rituximab and lenalidomide while maintaining acalabrutinib. With a median follow-up of approximately two years, the outcomes were highly promising: the overall response rate reached 100%, with a complete response rate of 90%. The two-year PFS and OS were reported at 82% and 96%, respectively. While longer-term data are necessary to confirm the durability of these responses, the trial adds to a growing body of evidence supporting chemo-free approaches in indolent lymphomas.