Advancements in Treatment Strategies for Relapsed/Refractory Diffuse Large B-Cell Lymphoma

At the 2025 Lymphoma, Leukemia & Myeloma (LL&M) Winter Symposium in Miami, Florida, Nilanjan Ghosh, MD, PhD, FACP, Atrium Health Levine Cancer Institute, Charlotte, North Carolina, shares recent advances in bispecific antibodies and CAR T-cell therapy for the treatment of patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL).

Transcript:

Hello, I'm Nilanjan Ghosh from Atrium Health Levine Cancer Institute in Charlotte, North Carolina, and Wake Forest School of Medicine in North Carolina. It’s a true honor and pleasure to be here at the LL&M Symposium in Miami, Florida. I have talked about relapsed/refractory diffuse large B-cell lymphoma. I'll share some highlights of the presentation with you today.

I focused my presentation on 3 components; 1, is on bispecific antibodies, another 1 is CAR T-cell therapy, and the third is on the ECHELON-3 study, looking at comparison of brentuximab and lenalidomide rituximab to rituximab and lenalidomide in relapsed/refractory DLBCL. It's been a really exciting year for lymphoma with lots of new developments.

One of the most important studies presented in 2024 was the STARGLO study, comparing patients with relapsed/refractory large B-Cell lymphoma, including those who had failed only 1 prior line of therapy, to glofitamab, gemcitabine oxaliplatin compared to rituximab, gemcitabine, oxaliplatin (R-GemOx).

In this study, there was a significant improvement in overall survival, which was the primary endpoint of the study, and improvement in progression-free survival and complete response rates with glofitamab, gemcitabine oxaliplatin over R-GemOx. This is an important study because it's being reviewed by the FDA and a decision is expected sometime in summer of 2025, so it could be very much practice changing.

Another study, which was updated at ASH 2024, was the use of glofitamab in relapsed/refractory DLBCL, which included patients with more than 2 prior lines of therapy. It showed that patients who had achieved a complete response (CR) with this time-limited therapy continued to be in long-term remission. Over 50% of the patients who had achieved a complete response, continued to be CR at more than 2 years. That's very important. More follow up will be needed to see if a proportion of these patients are potentially cured with this finite duration therapy.

Other studies which were also focusing on bispecific antibodies included, mosunetuzumab plus polatuzumab compared to rituximab and polatuzumab. Again, showing improvement in progression-free survival, as well as the response rates including CR with mosunetuzumab- polatuzumab. This is an important combination, it’s also being tested in another study called the SUNMO study, where we don't have results yet, but it's highly anticipated, comparing mosunetuzumab-polatuzumab with rituximab-GemOx in patients with relapse refractory D-L-B-C-L. So another study to look out for this year or in the the near future. 

I also presented results on a new bispecific antibody called AZD0486, which targets actually CD19, so a CD19-CD3 bispecific antibody. Again, this study includes patients who had failed traditional CD19 CAR T-Cell therapy, and it showed high responses as well as low toxicity. So, another promising molecule in this space.

Moving on to other treatments beyond bispecific antibodies, such as CAR T-Cell therapy. We saw really good, real-world studies from The Center for International Blood and Marrow Transplant Research (CIBMTR) looking at lisocabtagene maraleucel as well as axicabtagene ciloleucel, both as second line therapy in relapsed/refractory D-L-B-C-L. We saw really fantastic activity as well as a toxicity profile, which very much matched what was seen in clinical trials. Often in real world, we see actually worse outcomes, but in CAR T studies, we are seeing similar outcomes despite a large proportion of patients who are treated in the real world who would've not been candidates in the clinical trials. It's really reassuring to see this translation from clinical trial to the real world and yet maintaining the efficacy profile. 

Other groups which were very interesting and were presented at ASH was a very elderly group, even patients who are above age of 80, who got CAR T-Cell therapy. They compared that with patients who were 65 to 79 and showed really fantastic efficacy even in the octogenarian patients, which is very important because in the past, we would've not done transplant for these patients, but we know very well that CAR T eligibility is much broader than eligibility for autologous transplant. Looking at this elderly population and seeing the efficacy and toxicity in this profile is very helpful in our decision-making process.

Other things which I really focused on and try to summarize at the, at the symposium were “fast” CARs and “new” CARs. Looking at CAR T-cell therapies which take much shorter manufacturing time so you can deliver them quicker to these patients with aggressive lymphoma where time is of the essence. Also new targets, targets like CD22, bispecific CARs, and also metabolic CARs. There is a CAR T product, which is IL10 producing, that helps and has really great activity, and low toxicity. Long-term follow up will be needed, but several of these were presented at ASH. So a lot of good stuff to expect through the year.

Finally, I wanted to highlight the ECHELON-3 study, which is of brentuximab, lenalidomide, and rituximab compared to rituximab and lenalidomide plus placebo. This is a phase 3 randomized study, which showed improved overall survival and progression-free survival for patients who received brentuximab-rituximab, lenalidomide over rituximab-lenalidomide. This also included patients who were CD30^-.

It's a very good option, especially knowing that bispecific antibodies and CAR T-cell therapies are not yet available in many practices. Repurposing old drugs, which have been approved for over a decade and are now available, in clinical trials showed significant superiority. Hopefully people will be able to use this. In places where bispecifics and CAR Ts are available, I would suggest using this after failure of these agents because the efficacy is not as good in my mind as it is with bispecifics and CAR Ts, but certainly a very important addition to the armamentarium in this disease.

That’s a summary of my presentation, there are several clinical trials to look out for as well in the next year or so. Thank you so much for having me.

Source:

Ghosh N. Updates in Relapsed Diffuse Large B-Cell Lymphoma. Presented at Lymphoma, Leukemia & Winter Symposium; February 7-9, 2025. Miami, FL.