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Adding tafasitamab and lenalidomide to rituximab, cyclophosphamide, hydroxydaunomycin, oncovin, and prednisone (R-CHOP) improves outcomes in newly diagnosed diffuse large B-cell lymphoma and high-grade B-cell lymphoma, according to the phase 3 frontMIND trial.

Across almost 900 patients, the add-on improved progression-free survival (PFS) by a median of about 8 months at 2 years with a trend towards better overall survival (OS) vs R-CHOP alone. 

“We believe that the combination of tafasitamab, lenalidomide, and R-CHOP is a potential new standard frontline therapy. This study tells us that multiple antigen targeting in the frontline can lead to an improvement in meaningful clinical efficacy outcomes,” said lead investigator of the frontMIND trial,

Georg Lenz, MD, at the American Society of Clinical Oncology annual meeting.

Tafasitamab and lenalidomide are already on the US market for relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Lenz anticipates a frontline approval with R-CHOP given the trial results. 

R-CHOP — rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone/prednisolone — has been the standard frontline therapy for DLBCL and high-grade B-cell lymphoma for more than 20 years. Although curative for many patients, about 40% relapse or progress, highlighting the need for additional options, said Lenz, a lymphoma researcher at Münster University Hospital, Münster, Germany, while presenting the frontMIND results at the meeting.

There is already another frontline option, the Pola-R-CHP regimen, which adds the antibody-drug conjugate polatuzumab vedotin while removing vincristine. It was approved by the FDA in 2023 based on the POLARIX trial. 

Study discussant Krish Patel, MD, a lymphoma specialist at the Sarah Cannon Research Institute, Nashville, Tennessee, said the frontMIND results are important because the benefit of tafasitamab and lenalidomide plus R-CHOP (Tafa-Len-R-CHOP) seems to hold across molecular subgroups, which was not the case in POLARIX. 

“We’ll be interested to see the subgroups in more detail to see if this study leads to a more consistent effect,” he said. 

There’s also been no OS benefit for Pola-R-CHP after 5 years of follow-up. In contrast, Tafa-Len-R-CHOP has an edge over R-CHOP of about 4% at 3 years, but the OS difference hasn’t reached statistical significance. Lenz said he’s “hopeful” it will by the final OS readout at year 5. 

One concern with the new regimen is its potential impact on CD19 directed chimeric antigen receptor (CAR) T-cell therapy, a standard option in later lines. Tafasitamab is a CD19 antibody, but so far it doesn’t appear to impair subsequent CAR T responses. 

Patients “still express CD19 and still respond in the ballpark of what you would expect, but obviously we need much more data,” Lenz said. 

With two bispecific antibodies in development for the frontline setting — glofitamab in the SKYGLO trial and epcoritamab in the EPCORE DLBCL-2 trial — the future role of Tafa-Len-R-CHOP is also unclear.

“I think it will get approved, and I think it will be used. For how long, I don’t know because this really depends on the results of both trials. If they’re significantly superior, then I think tafasitamab will only play a temporary role. However, you never know. We will see,” Lenz said. 

FrontMIND randomized 448 patients to Tafa-Len-R-CHOP and 451 to R-CHOP for six treatment cycles. 

Two-year PFS was 71.1% with Tafa-Len-R-CHOP vs 62.9% with R-CHOP, an 8.2% difference; 3-year PFS was 67.3% vs 60.7%, a 6.6% difference. The PFS benefit held in both DLBCL molecular subtypes, ABC and GCB. 

Two-year OS was 84.1% with Tafa-Len-R-CHOP vs 80.5% with R-CHOP; 3-year OS was 81.1% vs 77.8%, respectively. The differences were not statistically significant. 

Infections, neutropenia, and anemia were more common with Tafa-Len-R-CHOP. Overall, 86.7% of patients developed grade 3 or worse treatment emergent adverse events vs 76.1% with R-CHOP. Adverse events were fatal in 5.9% of Tafa-Len-R-CHOP patients vs 3.8% of patients in the R-CHOP group. 

The trial was funded by Incyte, maker of tafasitamab. Among other industry ties, Lenz is an advisor and reported honoraria and travel expenses from the company. Patel is a researcher and advisor for Roche, AbbVie, Merck, Pfizer, and other companies. 

M. Alexander Otto is a physician assistant and award-wining journalist. He is also an MIT science journalism fellow. Email: aotto@medscape.net