Diffuse large B-cell lymphoma

At ICML, several important updates were presented regarding the treatment of diffuse large B-cell lymphoma (DLBCL), with a particular focus on novel therapeutic strategies for frail and elderly patients, as well as advances in the relapsed/refractory setting. Dr Gilles Crochet from CHU UCL Namur outlined key developments reflecting an evolving treatment landscape increasingly oriented toward chemo-free regimens and targeted antibody-based combinations.

In elderly and frail patients, where anthracycline-based chemotherapy is often contraindicated, three studies presented encouraging data on alternative treatment options. The first explored epcoritamab monotherapy in anthracycline-ineligible patients with newly diagnosed large B-cell lymphoma, reporting notably high complete response rates. A second study investigated the combination of glofitamab, polatuzumab vedotin and rituximab in a similar frail population, demonstrating highly promising response rates in the first-line setting. The third, the VERLen phase 2 trial, evaluated the combination of rituximab, tafasitamab and lenalidomide in frail patients considered eligible for R-CHOP. This regimen achieved a complete response rate of approximately 50%, with an overall response rate nearing 70%. Collectively, these findings suggest that chemo-free regimens may represent a feasible and effective approach in this vulnerable population, though longer-term outcomes and confirmatory studies are still required.

In the relapsed/refractory setting, updated results from several antibody-based combinations were presented. The STARGLO study provided a two-year follow-up, confirming sustained complete responses in a subset of patients, though it remains premature to determine whether these outcomes represent a plateau in disease control. Additionally, early data from the LOTIS-7 trial, a phase 1b study combining loncastuximab tesirine with glofitamab, revealed a complete response rate approaching 90%, indicating strong potential for this dual-antibody strategy despite the limited follow-up duration.

Another significant study, the phase 3 R-Pola-Glo trial, compared polatuzumab vedotin combined with GemOx versus GemOx alone in relapsed/refractory DLBCL. The combination arm demonstrated superior outcomes in both OS and PFS. However, its applicability in certain regions such as Belgium remains uncertain due to the routine use of polatuzumab vedotin in first-line regimens, leaving limited data on the efficacy of this agent in relapse following prior exposure.

Finally, in the frontline setting, preliminary results from a phase 2 trial evaluating R-CHP plus polatuzumab vedotin combined with glofitamab were presented. Despite the study’s small size (around 40 patients), the regimen achieved impressive response rates with sustained remissions. Larger phase 3 trials, such as the ongoing SKYGLO study, are expected to clarify the clinical value of incorporating bispecific antibodies into standard first-line regimens.