Changing Frontline Options for DLBCL

  • Frontline B‑cell lymphoma treatment is shifting beyond chemotherapy, with studies such as FrontMIND showing that adding immune‑based agents, such as tafasitamab, to R‑CHOP may boost efficacy and potentially increase cure rates.
  • Bispecific antibodies (e.g., epcoritamab) are rapidly moving earlier in treatment, offering a more practical, scalable alternative to CAR T-cell therapy. They’re being tested in combination regimens across both aggressive and indolent lymphomas.
  • The FrontMIND trial evaluated the addition of tafasitamab and lenalidomide, commonly referred to as tafa-len, to R-CHOP in previously untreated DLBCL. At two years, the progression-free survival (PFS) rate was 71.1% in the tafasitamab group compared to 62.9% in the group that received R-CHOP alone.
  • “The initial data that we’re hearing about and seeing is that this combination appears to improve the efficacy of the R-CHOP regimen. The hope is that it will cure more patients and prevent patients from relapsing,” Dr. John Leonard, Chief Clinical Officer at NYU Langone Health’s Perlmutter Cancer Center, tells SurvivorNet Connect.

Results from the FrontMIND study, presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, suggest that tafasitamab (Monjuvi) may play a key role in frontline treatment for patients with diffuse large B-cell lymphoma (DLBCL) — though longer follow-up will be needed before the regimen’s effect on survival is fully understood.

For decades, treatment in B-cell lymphomas has centered on chemotherapy-based regimens, with novel agents reserved for relapsed/refractory (R/R) disease. Increasingly, investigators are exploring whether targeted therapies and immunotherapies can improve outcomes when incorporated earlier. One of the clearest examples is the FrontMIND study, while ongoing research with bispecific antibodies such as epcoritamab highlights how the field is moving beyond chemotherapy alone across multiple lymphoma subtypes.

Dr. John Leonard, Chief Clinical Officer at NYU Langone Health’s Perlmutter Cancer Center, tells SurvivorNet Connect that therapies proven in relapsed disease are now being evaluated earlier, with the goal of improving long-term outcomes and increasing cure rates.

What Does the Data Say?

FrontMIND evaluated tafasitamab and lenalidomide (tafa-len) added to R-CHOP versus R-CHOP alone in previously untreated DLBCL.

“What this study is doing is combining tafasitamab-lenalidomide with the R-CHOP regimen and comparing that combination to R-CHOP alone,” Dr. Leonard explains.

The PFS results are encouraging:

  • Two-year PFS: 71.1% (tafa-len-R-CHOP) vs. 62.9% (R-CHOP)
  • Three-year PFS: 67.3% vs. 60.7%
  • A 25% reduction in the risk of disease progression or death

“The initial data is that this combination appears to improve the efficacy of the R-CHOP regimen. The hope is that it will cure more patients and prevent patients from relapsing,” Dr. Leonard says.

However, overall survival (OS) data remain immature. The OS hazard ratio was 0.85, which did not reach statistical significance (p=0.2703). Clinicians should note that the current evidence supports a PFS benefit — not a demonstrated survival advantage.

The Possibility of More Efficacy Comes With a Catch

The toxicity profile warrants careful consideration. Fatal treatment-emergent adverse events occurred in 6% of patients on tafa-len-R-CHOP versus 4% on R-CHOP alone. Grade ≥3 TEAEs were reported in 87% versus 76%, and serious TEAEs in 50% versus 39%.

Dr. Leonard frames the tradeoff plainly: “The goal is to improve the cure rates, and we know it’s going to add some side effects — but is the balance of the improved cure rate going to counteract those extra side effects? At this point, it does appear that that is the case, but we have to see the details of the data. If you’re curing more patients, you’re generally willing to accept a bit more toxicity. That’s the key balance in DLBCL.”

For clinicians, that calculus depends heavily on the OS question that remains open. A regimen with higher rates of treatment-related deaths and serious adverse events carries a different risk profile when survival benefit has not yet been confirmed.

The Evolving Role of Bispecific Antibodies

FrontMIND is part of a broader shift toward personalized frontline therapy. “DLBCL is moving from almost everybody getting R-CHOP to now subsets of patients getting variations,” Dr. Leonard notes.

Bispecific antibodies like epcoritamab, active in R/R disease, are now moving into earlier lines. “There are studies in aggressive lymphoma combining epcoritamab with chemotherapy and other regimens as part of initial therapy, both for DLBCL and for follicular lymphoma,” Dr. Leonard says. “The bispecific antibodies are easier to give than CAR T-cell therapy, and I think they’re more practical for a broader number of patients to receive.”

He expects immunotherapy-based combinations to keep advancing. “I do think we’ll be seeing more and more immunotherapies, more use of bispecifics, and probably less use of chemotherapy.”

FrontMIND represents a meaningful step in that direction — one that clinicians will be watching closely as OS data mature.

Natalie Rafaeli, MD is a specialist in malignant hematology, specifically with expertise in treating blood cancer. Dr. Rafaeli serves as an Assistant Professor in the McGovern Medical School Department of Internal Medicine. Her research focuses on developing novel treatment strategies. Dr. Rafaeli is board certified in Internal Medicine, Hematology, and Medical Oncology.

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