Professor Georg Lenz: Exploring the revolution in DLBCL first-line treatment

Despite repeated obstacles, the researchers' exploration has never stopped
.
How to build on the R-CHOP program, researchers try to individualize the treatment of patients according to their different characteristics and different treatment goals
.

The standard of care for the R-CHOP regimen is 6 cycles of CHOP regimen chemotherapy plus rituximab
.
Previous MInT trials have established a subgroup of patients with good prognosis, that is, patients aged 18~60, stage I/II, aaIPI=0, and no large
masses.
FLYER STUDY ⁷ ATTEMPTS TO REDUCE TOXICITY BY REDUCING THE CYCLE OF CHOP REGIMEN CHEMOTHERAPY IN PATIENTS WITH A GOOD PROGNOSIS AND MAINTAINING EFFICACY COMPARABLE TO STANDARD THERAPY (FIGURE 2).

Figure 2 FLYER study design

The FLYER study ultimately analysed 588 young patients with a good prognosis, with a median follow-up of 66 months, and showed that the standard 6-cycle R-CHOP regimen was comparable to the 4-cycle R-CHOP + 2-cycle R regimen (3-year PFS rate 94% vs.
96%; The three-year OS rate was 98% vs.
99%), and there was no significant difference in recurrence between the two groups (5% vs.
4%)
.

Figure 3 FLYER RESEARCH RESULTS: PFS AND OS

Thus, in young patients with DLBCL with a good prognosis, first-line therapy without compromising prognosis may reduce the duration
of chemotherapy.

POLARIX ^STUDY8 IS A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED GLOBAL PHASE III CLINICAL STUDY
.
A total of 879 patients with treatment-naïve DLBCL between 18~80 years old and IPI score 2-5 were included, with a median age of 65 years and about 70% of patients > 60 years old.
62% of patients had an IPI score of 3 to 5
.
Randomized 1:1 to receive 6 cycles of Pola-R-CHP or R-CHOP, followed by 2 cycles of rituximab monotherapy (Figure 4).

FIGURE 4 POLARIX STUDY DESIGN

At a median follow-up of 28.
2 months, PFS was significantly improved in the Pola-R-CHP group compared with the R-CHOP group, reducing the relative risk of disease progression, recurrence, or death by 27% (HR 0.
73; 95% CI: 0.
57-0.
95; P<0.
02).

The 2-year PFS rate in the Pola-R-CHP group increased by 6.
5% (76.
7% vs 70.
2%) compared with the R-CHOP group (Figure 5).

FIGURE 5 POLARIX STUDY: PFS RATE AT 2 YEARS

Subgroup analysis showed that Pola-R-CHP benefited more significantly in patients with clinical high-risk factors or molecular characteristics, such as IPI score of 3-5, age > 60 years, and ABC subtype (Figure 6).

FIG.
6 POLARIX STUDY: 2-YEAR PFS RATE SUBGROUP ANALYSIS

The event-free survival (EFS) results showed that the POLA-R-CHCP group had a higher EFS rate (75.
6% vs.
69.
4%, HR 0.
75; 95% CI: 0.
58-0.
96; P=0.
02) (Figure 7), suggesting that the Pola-R-CHP group had a lower relative risk of events than the R-CHOP group
.

FIGURE 7 POLARIX STUDY: EFS

Disease-free survival (DFS) results showed (Figure 8) that the Pola-R-CHP group had a longer duration of response than the R-CHOP group (HR 0.
70; 95% CI: 0.
50-0.
98).

FIGURE 8 POLARIX STUDY: DFS

Because the Pola-R-CHP regimen is more effective, fewer patients in the Pola-R-CHP group receive subsequent anti-lymphoma therapy than the R-CHOP group, including at least one subsequent anti-lymphoma therapy, radiotherapy, stem cell transplantation, and CAR-T cell therapy
.

Fig.
9 Pola-R-CHP vs R-CHOP: receiving subsequent anti-lymphoma therapy

Professor Georg Lenz emphasized that although both regimens can cure some patients, the Pola-R-CHP regimen is more effective, and there are no additional safety events, and patients can be cured
without the need for more subsequent treatments.
The Pola-R-CHP regimen is clinically important for the first-line treatment of DLBCL and is currently approved in Europe and included in the latest guideline recommendations in Germany in ²⁰²²⁹ (Figure 10).

Figure 10 German DLBCL treatment guidelines