Seeking a share of the first-line diffuse large B-cell lymphoma (DLBCL) market, Incyte believes Monjuvi’s positive phase 3 results across patient subgroups will give it an edge over the standard R-CHOP regimen and Roche’s Polivy—at least until newer agents 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 has shown.
While the median progression-free survival (PFS) time was not reached after a median follow-up of 35.2 months, 67.3% of patients in the Monjuvi arm and 60.7% in the R-CHOP group were estimated to be alive and free of progression by three years, according to results to be presented at the American Society of Clinical Oncology 2026 annual meeting.
Among patients with centrally confirmed diagnoses, the Monjuvi combo’s PFS improvement over R-CHOP was 32%.
In first-line DLBCL, a PFS improvement is “likely to lead to an improvement in long-term curative outcomes,” Krish Patel, M.D., executive director of hematologic cancer research at the Sarah Cannon Research Institute and an ASCO expert in lymphoma, said in a statement.
The positive frontMIND readout puts Incyte on a collision course with Roche in first-line DLBCL. Polivy, used alongside 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% PFS improvement over R-CHOP. Polivy is a CD79b-directed antibody-drug conjugate, whereas Monjuvi is a regular CD19 monoclonal antibody.
Roche’s regimen holds an obvious advantage—it only contains five drugs, compared with seven for Incyte’s offer.
But Incyte’s president and global head of R&D, Pablo Cagnoni, M.D., argued that some additional infusion burden may be worthwhile in exchange for a better potential for a cure, especially given that R-CHOP has historically been hard to beat.
“In general, in the curative setting, if you think the patient can tolerate it, you go for the best option first,” Cagnoni told Fierce in an interview.
With its B-cell-depleting mechanism, Monjuvi comes with some increased risk of infection. Still, Cagnoni described it as “a relatively well-tolerated drug.”
In frontMIND, grade 3 or above treatment-emergent adverse events (TEAEs) occurred more frequently in the Monjuvi arm (86.7%) than in the control cohort (76.1%). Nevertheless, TEAEs only led to treatment discontinuations in 5.2% of those in the Monjuvi group, versus 5.4% for R-CHOP. Besides, the addition of Monjuvi and lenalidomide did not affect patients’ ability to receive R-CHOP, lead study author Georg Lenz, M.D., from University Hospital Münster in Germany, told reporters during a press briefing.
But even more important for Monjuvi’s profile is what Lenz and Cagnoni called a consistent benefit across patient subgroups.
In the Polarix trial, Polivy-R-CHP showed no benefit in germinal center b-cell-like (GCB), one of the two primary molecular subtypes of DLBCL. If approved, Monjuvi could fill that gap, Cagnoni argued.
The FDA also initially had some reservations about Polivy-R-CHP because it didn’t show any overall survival (OS) benefit. Lenz is hopeful that Monjuvi-lenalidomide-R-CHOP could differentiate here, too.
At the current interim analysis, the Monjuvi combo showed a preliminary 15% OS improvement, which was not statistically significant. Three-year OS rate was 81.1% with the Incyte therapy, versus 77.8% with R-CHOP. The final OS analysis is expected in about two years, according to Lenz.
Monjuvi and lenalidomide initially got an accelerated approval in second-line DLBCL in 2020 based on tumor shrinkage data from a single-arm study. Now, with the randomized frontMIND trial, questions remain as to whether both drugs are needed in the first-line combo.
Between the two agents, existing clinical evidence already suggests that lenalidomide alone may not achieve much on top of R-CHOP in first-line DLBCL. In terms of whether Monjuvi needs extra help, Cagnoni noted that Incyte has mechanistic preclinical data that suggests lenalidomide enhances the CD19 antibody greatly.
Incyte is trying to establish Monjuvi as a new standard of care in first-line DLBCL as a group of CD20 T-cell engagers are on its tail. These include AbbVie and Genmab’s Epkinly, whose Epcore DLBCL-2 trial is expected to read out this year; and Roche’s Skyglo trial for Columvi and Polivy-R-CHP could report data next year.
As for Incyte’s potential countermeasure, while Cagnoni stressed that hematology is “the soul of the company” and will always be a key priority, the Jakafi maker currently does not have a follow-up DLBCL program in mid- to late-stage development.