Frontline Targeted Therapies Plus R-CHOP Boosts PFS in High-Risk B-Cell Lymphomas

CHICAGO — Combining two targeted therapies with standard-of-care chemotherapy extended progression-free survival (PFS) in patients with newly diagnosed B-cell lymphomas, according to data from the frontMIND trial.

In the phase III study, tafasitamab (Monjuvi) and lenalidomide (Revlimid) were added to R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) for frontline therapy in patients with untreated high-risk diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma (HGBL).

At a median follow-up of 35.2 months, treatment with the combination regimen reduced the risk of progression by 25%, compared with R-CHOP alone, for a median PFS that was not reached (HR 0.75, 95% CI 0.59-0.96, P=0.0194), according to Georg Lenz, MD, PhD, of the University Hospital Münster in Münster, Germany.

The 2-year PFS was 71.1% with the combination versus 62.9% with R-CHOP, while the 3-year PFS rates were 67.3% and 60.7%, respectively, he reported at a press briefing at the American Society of Clinical Oncology (ASCO) annual meeting.

PFS benefit (primary endpoint) was seen in both activated B-cell-like-type and germinal center B cell-like-type DLBCL, according to Lenz, who noted that “we believe the combination of tafasitamab and lenalidomide and CHOP is a potential new standard or frontline therapy” in high-risk DLBCL or high-grade HGBL.

“Most importantly, the addition of tafasitamab and lenalidomide did not affect the delivery of the important backbone, R-CHOP,” he observed. Median relative dose intensities remaining high and “the same for both treatment groups across 6 cycles for each R-CHOP component,” Lenz and colleagues stated.

ASCO discussant Krish Patel, MD, of the Sarah Cannon Research Institute in Nashville, Tennessee, pointed out that “for more than 2 decades, R-CHOP has been the global standard of care for newly diagnosed patients with DLBCL, leading to cure in about 60% of patients. Unfortunately it has been difficult to advance on that paradigm, and frontMIND represents only the second phase III study to meet its primary endpoint in the last 2 decades.”

The other trial, POLARIX, showed that substituting polatuzumab vedotin (Polivy) for vincristine in the R-CHOP regimen significantly improved PFS versus R-CHOP. Those data led to FDA approval of the combination for adult patients who have previously untreated DLBCL, not otherwise specified, or HGBL.

Patel also stressed that the improved PFS with the combination regimen “is expected to lead to an improvement in curative outcomes for these patients, and it’s encouraging to see that the delivery of the curative therapy R-CHOP was not compromised by the addition of two new agents.”

Lenz pointed out that about 40% of patients — particularly those with high-risk disease — are not cured with first-line R-CHOP, so “we need better treatments, especially for these high-risk patients.”

Tafasitamab is a monoclonal antibody that targets CD-19 protein, a surface marker that is expressed on both normal and malignant B cells.

“Tafasitamab has been shown preclinically, and also clinically, to kill malignant B cells,” Lenz stated, adding that the combination of tafasitamab and lenalidomide has also been effective in patients with relapsed/refractory DLBCL. It is FDA approved for that indication. The tafasitamab-lenalidomide-R-CHOP regimen also was tested in the phase Ib First-MIND trial.

The frontMIND study included 899 adults with previously untreated high-risk DLBCL or HGBL who received either of the two regimens for six 21-day cycles.

Other trial endpoints were a complete response in 65.2% of patients in both groups, along with an overall response rate of 80.4% in the combination group versus 76.1% in the R-CHOP group. Also, event-free survival significantly improved with the former versus the latter treatment (HR 0.79, 95% CI 0.64-0.97, P=0.0260). An interim overall survival showed a trend in favor of the combination (HR 0.85, 95% CI 0.63-1.14, P=0.2703).

As for safety, the most common adverse events (AEs) were cytopenias and infections in both groups. Any-grade treatment-emergent AEs (TEAE) were similar in the two groups, although grade ≥3 TEAEs were higher in the combination group versus the R-CHOP group (86.7% vs 76.1%, respectively).

AEs led 25.7% in the combination group to discontinue part of treatment versus 17.9% in the R-CHOP group, while about 5% in both groups stopped treatment altogether.