How Are Key Lymphoma Data From ASCO and EHA 2026 Shaping Treatment?

Treatment of aggressive and indolent B-cell lymphomas continues to evolve rapidly, with novel bispecific antibodies, engineered cellular therapy platforms, and new frontline combination regimens generating significant data across both the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting and the 2026 European Hematology Association (EHA) Congress.

CancerNetwork® spoke with Matthew Matasar, MD, chief in the division of Blood Disorders, Rutgers Cancer Institute/Jack & Sheryl Morris Cancer Center, and professor of medicine at Rutgers Robert Wood Johnson Medical School, about standout lymphoma data from both meetings, how those findings may influence clinical decision-making, and where the field is headed next.

Matasar began by identifying the highlights in aggressive B-cell lymphoma from the ASCO annual meeting, anchored by primary results from the phase 3 frontMIND trial (NCT04824092) of tafasitamab (Monjuvi) plus lenalidomide (Revlimid) and rituximab (Rituxan) with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in newly diagnosed high-risk diffuse large B-cell lymphoma (DLBCL), which were concurrently published in The Lancet.¹ He then highlighted his key EHA takeaway: the initial safety run-in data from the phase 3 SOUNDTRACK-F1 trial (NCT06549595) of surovatamig (AZD0486) in previously untreated follicular lymphoma.² Matasar then walked through how he is interpreting the frontMIND data relative to the phase 3 POLARIX trial (NCT03274492) and the considerations that will shape frontline patient selection.³

He turned next to early ASCO data from the phase 2 study (NCT06045247) of epcoritamab-bysp (Epkinly) plus rituximab, cyclophosphamide, vincristine, and prednisone (R-miniCVP) in elderly and frail patients with newly diagnosed DLBCL, before discussing the engineering significance of the CONQUER trial (NCT06874946) and its approach to overcoming T-cell fratricide in CAR-T therapy for T-cell malignancies.⁴,⁵ Matasar closed by sharing his outlook on the parallel bispecific antibody strategies underway to move chemotherapy-free treatment into the frontline follicular lymphoma setting.

CancerNetwork: What were the highlights in lymphoma from the 2026 ASCO Annual Meeting?

Matasar: There was a lot of progress reported at ASCO this year. Some of the highlights really center on the management of aggressive B-cell lymphoma. We have data from the frontMIND trial, which are very interesting and were concurrently published in The Lancet. We are all trying to wrap our heads around what this might mean for our field. There were also some encouraging data about novel strategies in treating elderly or less-fit patients with large cell lymphoma, and some emerging data around new targets and new mechanisms of action as we continue to try to expand our therapeutic armamentarium.

What unique findings emerged from EHA 2026, and what were the key takeaways from that meeting?

Sometimes EHA exists in the shadows of ASCO. There were some new data presented at EHA this year that were new to us. One I was particularly impressed by was the presentation of the initial safety run-in from the SOUNDTRACK-F1 trial, presented by Chan Cheah, MBBS, FRACP, FRCPA, DMSc, and colleagues, looking at first-line therapy with surovatamig, the novel CD19-directed bispecific antibody, in the treatment of newly diagnosed, previously untreated follicular lymphoma.

The frontMIND trial established a progression-free survival [PFS] advantage for the tafasitamab-lenalidomide-R-CHOP triplet in high-risk DLBCL. How should community and academic oncologists select which high-risk patients should receive this regimen vs standard R-CHOP?

A lot of us are digesting these data right now. There are important methodological elements that need to be understood. This was, as you indicated, a study looking at patients with high-intermediate risk or high-risk disease with an IPI [International Prognostic Index] score of 3 or more—a narrower, risk-enriched population compared with the POLARIX trial. It was compared to an R-CHOP program, as opposed to a pola-R-CHP [polatuzumab vedotin-piiq (Polivy) plus R-CHP]-based program, and it added tafasitamab, the CD19 monoclonal antibody, and lenalidomide on top of R-CHOP vs R-CHOP alone. This is different from the POLARIX trial, where we had substitution yielding 2 programs with very similar toxicity profiles. Here we are adding tafasitamab-lenalidomide with additional toxicities from those drugs, as well as logistical challenges regarding the treatment schedule, particularly with respect to lenalidomide.

The study was positive for its primary end point of PFS, with a 25% lower risk of progression or death. When a study is positive for its primary end point, it is going to get everyone’s attention. It achieved this, however, without yet demonstrating a statistically significant overall survival [OS] benefit. So here we have a situation where there is a PFS benefit without an OS benefit, with incremental toxicity and scheduling challenges that we are going to have to weigh. There may be a role for tafasitamab-lenalidomide-R-CHOP in the treatment of some subset of patients with high-risk large B-cell lymphoma who wish to pursue a more intensive treatment program, and for whom the treating oncologist may prefer R-CHOP over a pola-R-CHP–based approach. Who exactly those patients are remains to be seen.

Given the promising data surrounding epcoritamab plus R-miniCVP for patients deemed unfit or frail with DLBCL, do you see this non-anthracycline, bispecific-driven approach completely replacing standard attenuated chemotherapy in the frontline?

In the short term, the answer is absolutely not. But I am very much encouraged by these strategies. Broadly speaking, I love that our field is taking an ambitious swing at how best to take care of patients who are older and less fit with large cell lymphoma. This is a disease that is more common as we age, and older, frail, or unfit patients have been tremendously underserved historically by our therapeutic research programs. This is a very nice step forward. We are getting rid of the anthracycline, and a CD20 bispecific antibody combined with CVP chemotherapy instead of CHOP is yielding very impressive early results. It is a small, exploratory study with short follow-up, but very encouraging.

It paints a way forward in which we will be using bispecific antibodies more as a way to leverage their efficacy and to try to limit the short- and long-term toxicities of chemotherapy in this frail patient population. Whether this is the right combination or whether it is going to be glofitamab [Columvi] plus polatuzumab vedotin-piiq or whether it is going to be mosunetuzumab [Lunsumio] monotherapy in an untreated population as in the phase 2 MorningSun trial [NCT05207670], there are a lot of strategies that we are deploying, and I am very encouraged by our progress.⁶

The CONQUER trial was highlighted for its sophisticated engineering to prevent CAR-T fratricide. For cell therapy coordinators, pathologists, and transplant physicians, what does this engineering milestone mean for the future of CAR-T in T-cell malignancies, and how did the manageable cytokine release syndrome profile look in practice?

It is very exciting. CAR T-cell therapy has altered the therapeutic landscape in the treatment of many types of B-cell lymphoma, most notably DLBCL, where it has become the standard of care in the second-line setting for most patients. We have had a lot of difficulty achieving those types of results with other forms of lymphoma, including T-cell lymphoma and classical Hodgkin lymphoma. This is a meaningful step forward—an early-phase study that was able to yield meaningful results and an acceptable and manageable safety profile.

It has been challenging because when you are trying to kill malignant T cells, you do not want the therapeutic CAR T-cells killing each other. This fratricide phenomenon has been a difficult hurdle for the field to overcome. There are a number of different ways to address it in terms of engineering the cells. This is a very attractive approach, and it demonstrates feasibility, not just for this one cellular product, but it gives us increased optimism that the field will continue to evolve and offer novel approaches to treating relapsed T-cell lymphoma, which continues to carry a very grave prognosis, even in this modern era.

How close are we to potentially retiring bendamustine-rituximab [BR] or R-CHOP for high-tumor-burden follicular lymphoma given the emergence of bispecifics? And what are the primary safety and sequencing challenges the multidisciplinary team must anticipate if T-cell engagers move to the frontline?

The first part of your question is how close we are to getting rid of chemotherapy. I would say that we are trying—we are obviously not there yet, but we are trying. There are a number of pivotal studies exploring bispecific antibodies in the first-line setting that hold great promise. It makes sense on paper: giving these drugs to treatment-naive immune systems, to T cells that have not been altered by prior treatments, including bendamustine, which is notably T-cell toxic, is inherently attractive. We have some limited exposure and experience already demonstrating safety and efficacy in this context, with good activity and low rates of toxicity. All very encouraging.

We are pursuing this in a number of different ways. We have mosunetuzumab monotherapy for low-tumor-burden follicular lymphoma in the phase 3 SWOG S2308 study [NCT06337318], epcoritamab plus R2 [rituximab plus lenalidomide] being evaluated vs chemoimmunotherapy and maintenance, and surovatamig, which we referenced earlier, being compared to chemotherapy as monotherapy in the SOUNDTRACK-F1 trial. There’s a lot of different parallel strategies as we are trying to figure out which are our best drugs, which are the right patients, and how we can most effectively expand this approach.⁷

I am encouraged by the pace of community adoption of bispecific antibodies—not just in lymphoma, where we have seen a very nice uptake over the last year—but certainly being driven as well by the adoption of bispecifics in other disease states, including solid malignancies. This is one of those rising-waters-lift-all-ships scenarios, in my opinion. As the broader need to deploy these agents grows, the lymphoma community is going to benefit from wider adoption, and my expectation is that by the time these studies read out positively in the years to come, we will have an oncology community that is ready to meet that data where it is and deploy it in the best service of our patients.

References

1. Lenz G, Trněný M, Burke JM, et al. Tafasitamab plus lenalidomide and R-CHOP vs R-CHOP for first-line treatment of patients with high-risk diffuse large B-cell lymphoma (frontMIND): a global, phase 3, randomised, double-blind, placebo-controlled trial. Lancet. 2026;407(10547):2528-2541. doi:10.1016/S0140-6736(26)00866-4

2. Cheah CY, Wojtowicz MM, Yoon DH, et al. Surovatamig (AZD0486) plus rituximab in previously untreated follicular lymphoma (FL): initial safety data from the phase 3 SOUNDTRACK-F1 trial. Presented at: European Hematology Association 2026 Congress; June 11-14, 2026; Stockholm, Sweden. Abstract S228

3. Tilly H, Morschhauser F, Sehn LH, et al. Polatuzumab vedotin in previously untreated diffuse large B-cell lymphoma. N Engl J Med. 2022;386(4):351-363. doi:10.1056/NEJMoa2115304

4. Chihara D, Chauhan A, Lin R, et al. Phase 2 trial of epcoritamab in combination with rituximab-mini CVP for older unfit/frail or anthracycline-ineligible adult patients with newly diagnosed diffuse large B-cell lymphoma: interim futility analysis. J Clin Oncol. 2026;44(suppl 16):7002. doi:10.1200/JCO.2026.44.16_suppl.7002

5. Lv M, Wang L, Mingkun W, et al. First-in-human dual-epitope nanobody anti-CD5 CAR-T for relapsed/refractory T-ALL/PTCL: phase I dose-escalation and expansion results from the CONQUER trial. J Clin Oncol. 2026;44(suppl 16):6508. doi:10.1200/JCO.2026.44.16_suppl.6508

6. Flinn IW, Burke JM, Sharman JP, et al. Fixed duration subcutaneous (SC) mosunetuzumab (Mosun) in patients with previously untreated high-tumor burden follicular lymphoma (FL): interim results from the phase II MorningSun study. J Clin Oncol. 2025;43(suppl 16):7014. doi:10.1200/JCO.2025.43.16_suppl.7014

7. Comparing rituximab and mosunetuzumab drug treatments for people with low tumor burden follicular lymphoma. ClinicalTrials.gov. Updated June 17, 2026. Accessed June 22, 2026. https://tinyurl.com/y8pktbu9