Tafa-Len + R-CHOP induces deeper remissions than R-CHOP alone in patients with B-cell lymphomas.In the global phase III frontMIND study, adding tafasitamab and lenalidomide (Tafa-Len) to an R-CHOP* chemotherapy regimen significantly improves progression-free survival in patients with previously untreated high-risk diffuse large B-cell lymphoma (DLBCL) and high-grade BCL (HGBCL).
The primary endpoint was met—Tafa-Len + chemo resulted in a significant 25-percent reduction in the risk of disease progression or death compared with chemo only (hazard ratio [HR], 0.75; p=0.019), with an 8.2-percent difference in the 2-year PFS rate in the overall population (71.1 percent vs 62.9 percent) and a 10.5-percent difference in patients with centrally confirmed lymphoma subtypes (72.7 percent vs 62.2 percent; HR, 0.68; nominal p=0.003) after a median follow-up of 35.2 months, noted Dr Georg Lenz from the University Hospital Münster, Germany.
A trend towards PFS benefit was consistently observed in prespecified subgroups, including activated B-cell–like (HR, 0.59) and germinal centre B-cell–like (HR, 0.69) molecular cell-of-origin (COO) subtypes per central gene expression profiling.
Investigator-assessed event-free survival (EFS) was also significantly better in the experimental vs the control group (HR, 0.79; p=0.026), with 2-year EFS rates of 65 percent and 56.7 percent, respectively. [EHA 2026, abstract S101]
The interim analysis also showed a positive overall survival (OS) trend with Tafa-Len + chemo vs chemo alone after a median follow-up of 35.9 months (2-year OS rates, 84.1 percent vs 80.5 percent; HR, 0.85; p=0.270).
Objective response rates (ORRs) were similar between the investigational and control groups at end of treatment (80.4 percent vs 76.1 percent; odds ratio [OR], 1.29; nominal p=0.120), as were PET-negative complete response rates (65.2 percent for both; OR, 1.00; p=0.987)
MRD-negativity rate was higher with the experimental regimen than with the control regimen (81.3 percent vs 66.7 percent), implying that Tafa-Len + R-CHOP induces deeper remissions than R-CHOP alone, Lenz said.
Safety, R-CHOP delivery
Grade ≥3 treatment-emergent adverse event (TEAE) rate was higher with Tafa-Len + chemo than with chemo alone (86.7 percent vs 76.1 percent), but both groups had similar proportions of TEAEs leading to discontinuation of all treatment components (5.2 percent vs 5.4 percent).
Fatal TEAEs were mostly balanced between the experimental and control groups (5.9 percent vs 3.8 percent), but there were fewer deaths overall in the former vs the latter group (18.5 percent vs 21.7 percent).
In the investigational group, the most frequent TEAE was neutropenia (70.7 percent), followed by anaemia (46.3 percent). Of note, 13.3 percent of participants had serious febrile neutropenia.
Median relative dose intensities were high and similar in both groups across six treatment cycles for each R-CHOP component: ≥92 percent for vincristine and 100 percent for each of the other components in both groups.
“The incremental safety events observed with Tafa-Len + chemo were well-managed and did not compromise the delivery of the R-CHOP backbone which, I think, is really important,” noted Lenz.
A new standard 1L Tx option?
Approximately 40 percent of individuals with high-risk DLBCL are not cured with first-line (1L) R-CHOP, underscoring the need for novel therapeutic 1L strategies to improve outcomes. [Blood 2010;116:2040-2045; N Engl J Med 2002;346:235-242; J Clin Oncol 2025;43:3698-3705]
Evidence shows that Tafa-Len doubled the historical ORR of lenalidomide monotherapy in relapsed/refractory DLBCL, leading to its US FDA approval in this setting. [Lancet Oncol 2020;21:978-988; Front Oncol 2021;11:756728]
“The combination of Tafa-Len and R-CHOP was evaluated in the phase 1B First-MIND study … Although small, the study still showed encouraging efficacy and safety data to embark on the frontMIND study,” Lenz said. [Blood 2023;142:1348-1358]
In frontMIND, Lenz and colleagues evaluated Tafa-Len + R-CHOP in individuals with untreated high-intermediate or high-risk aggressive BCLs. A total of 899 participants (median age 65 years, 52.6 percent men) were randomized 1:1 to six cycles of R-CHOP with or without Tafa-Len. Tafasitamab was administered intravenously at 12 mg/kg on days 1, 8, and 15, while lenalidomide was given orally at 25 mg daily on days 1–10.
Approximately 44 percent of participants had high-risk disease (IPI 4–5/aaIPI** 3), 38.7 percent had extranodal involvement at ≥2 sites, 53.9 percent had bulky disease, and 82.9 percent had elevated lactate dehydrogenase levels.
“[Taken together,] Tafa-Len plus R-CHOP represents a potential new standard 1L treatment for patients with high-risk DLBCL or HGBCL regardless of COO molecular subtype,” Lenz concluded.