Insight, which is aiming to gain share in the first-line diffuse large B-cell lymphoma (DLBCL) market, believes Monjuvi’s positive Phase 3 results across patient subgroups give it an advantage over the standard R-CHOP regimen and Roche’s Polivy, at least until newer drugs such as T-cell engagers catch up.
The addition of Monjuvi and lenalidomide (Revlimid) to R-CHOP reduced the risk of disease progression or death by 25% in previously untreated patients with high-intermediate or high-risk DLBCL and high-grade B-cell lymphoma, the phase 3 frontMIND study showed.
Although median progression-free survival (PFS) was not reached after a median follow-up of 35.2 months, 67.3% of patients in the Monjuvi group and 60.7% of patients in the R-CHOP group were estimated to be alive and progression-free by 3 years, according to the results to be presented at the 2026 Annual Meeting of the American Society of Clinical Oncology.
Among patients with centrally confirmed diagnosis, the PFS improvement rate for Monjuvi Combo versus R-CHOP was 32%.
In first-line DLBCL, improved PFS is “likely to translate into improved long-term outcomes,” Krish Patel, MD, of the Sarah Cannon Institute and an ASCO expert in lymphoma, said in a statement.
The positive front MIND result puts Insight on a collision course with Roche in the front-line DLBCL. Polivy, used in combination with R-CHP, was approved by the FDA in this setting in 2023 after the Phase 3 Polarix trial linked the Roche regimen to a 27% improvement in PFS over R-CHOP. Polivy is a CD79b-directed antibody-drug conjugate, while Monjuvi is a regular CD19 monoclonal antibody.
Roche’s regimen has clear advantages. It only includes five drugs, compared to seven in the Insight proposal.
However, Pablo Cagnoni, MD, Incyte’s president and global head of research and development, argued that some additional injection burden may be worth it in exchange for a better chance of treatment, especially considering that R-CHOP has historically been difficult to beat.
“Typically, in a therapeutic setting, you choose the best option first if you think the patient can tolerate it,” Cagnoni told Fiers in an interview.
Monjuvi has a mechanism to deplete B cells, which increases the risk of infection to some extent. Still, Cagnoni described it as a “relatively well-tolerated drug.”
In FrontMIND, treatment-emergent adverse events (TEAEs) of grade 3 or higher occurred more frequently in the Monjuvi group (86.7%) than in the control cohort (76.1%). Nevertheless, TEAEs led to treatment discontinuation in only 5.2% of the Monjuvi group compared with 5.4% of the R-CHOP group. Moreover, the addition of Monjuvi and lenalidomide did not affect patients’ ability to administer R-CHOP, study lead author Georg Lenz, MD, of the University Hospital Münster in Germany, told reporters at a press conference.
But even more important to Monjuvi’s profile is what Lenz and Cagnoni called consistent benefits across patient subgroups.
In the Polarix trial, Polivy-R-CHP had no effect on germinal center B cell-like (GCB), one of the two major molecular subtypes of DLBCL. If approved, Cagnoni argued, Monjuvi could fill that gap.
The FDA also initially had some concerns because Polivy-R-CHP did not show an overall survival (OS) benefit. Lenz hopes Monjuvi-lenalidomide-R-CHOP can differentiate here as well.
In the current interim analysis, the Monjuvi combo showed a preliminary 15% OS improvement, but this was not statistically significant. The 3-year OS rate was 81.1% with Incyte therapy versus 77.8% with R-CHOP. The final OS analysis is expected to be completed within about two years, Lenz said.
Monjuvi and lenalidomide received accelerated approval in second-line DLBCL in 2020 based on tumor regression data in single-arm trials. Now, in the randomized frontMIND trial, questions remain about whether both drugs are needed in the first-line combination.
Of the two agents, existing clinical evidence already suggests that lenalidomide alone may be less effective in addition to R-CHOP in first-line DLBCL. As for whether Monjuvi needs additional support, Cagnoni noted that Incyte has mechanistic preclinical data suggesting that lenalidomide significantly enhances CD19 antibodies.
As the CD20 T-cell engager group continues to emerge, Incyte is establishing Monjuvi as the new standard of care in first-line DLBCL. These include AbbVie and Genmab’s Epkinly, whose Epcore DLBCL-2 trial is expected to have results this year. Additionally, Roche’s Skyglo trials for Columvi and Polivy-R-CHP are likely to report data next year.
Regarding Insight’s potential countermeasures, Cagnoni emphasized that hematology is the “soul of the company” and will always be a key priority, but the Jakafi manufacturer currently does not have a follow-up DLBCL program in mid-to-late stage development.
