Chinese Medical Team Research: 64.6% Complete Remission Rate, Over Half of Patients Progression-Free for More Than Two Years! Targeted Therapy Combined with Chemotherapy is Safe and Effective as First-Line Treatment for Lymphoma

**Chinese Medical Team Research: 64.6% Complete Remission Rate, Over Half of Patients Progression-Free for More Than Two Years! Targeted Therapy Combined with Chemotherapy is Safe and Effective as First-Line Treatment for Lymphoma**

Lymphoma

Peripheral T-cell lymphoma (PTCL) is a group of highly aggressive and heterogeneous diseases with poor prognosis. The standard CHOP regimen (cyclophosphamide, doxorubicin, vincristine, and prednisone) is widely used as first-line treatment for PTCL. Previous studies have confirmed the safety and efficacy of combining various targeted drugs with CHOP (CHOPX) for PTCL treatment. However, there are multiple PTCL subtypes with different mutations, such as TP53, TET2, KMT2D, and CREBBP/EP300, and evidence is still lacking regarding the effectiveness of these combined treatment regimens in patients with specific genetic mutations.

Recently, a Chinese study published in *The Lancet Regional Health–Western Pacific* showed that selecting targeted therapies based on specific genetic mutations, combined with CHOP as a first-line treatment for PTCL, demonstrated good efficacy and safety. Compared to standard CHOP, CHOPX treatment achieved a higher complete remission rate and longer progression-free survival. This study was conducted by a Chinese medical team.

This was an open-label, multi-center, non-randomized, external-controlled phase 2 clinical trial (code-named GUIDANCE-03) conducted across seven medical centers in China. The trial compared the efficacy and safety of targeted drug combinations based on specific genetic mutations with CHOP (CHOPX) versus CHOP alone in newly diagnosed PTCL patients.

A total of 96 newly diagnosed PTCL patients (aged ≥18 years, median age 63 years) were enrolled in the study, with 48 patients in each group (CHOPX and CHOP). Genetic sequencing results showed that 93 patients (96.9%) carried genetic mutations. Patients in the CHOPX group received standard CHOP treatment during the first treatment cycle. Starting from the second cycle, targeted drugs were added based on the patient’s specific genetic mutations: decitabine (for TP53 mutations), azacitidine (for TET2/KMT2D mutations), chidamide (for CREBBP/EP300 mutations), and lenalidomide (for patients without these mutations), with a total of six treatment cycles. Patients in the CHOP group received six cycles of CHOP treatment.

The primary endpoint of the study was the complete remission rate (CRR) at the end of treatment. Secondary endpoints included overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. The analysis results showed:

– At the end of treatment, the CRR of the CHOPX group was superior to that of the CHOP group. Compared to the CHOP group, the CHOPX group saw an approximate 30% improvement in CRR (64.6% vs. 33.3%, OR 0.27, 95% CI 0.12-0.64; P=0.004), achieving the primary endpoint of the study.

– For secondary endpoints, the ORR of the CHOPX group was better than that of the CHOP group (66.7% vs. 52.1%).

– During a median follow-up period of 24.3 months, the median PFS of the CHOPX group was significantly longer than that of the CHOP group (25.5 months vs. 9.0 months; HR 0.57, 95% CI 0.34-0.98; P=0.041), with a 43% reduction in the risk of disease progression or death. The 2-year PFS rates for the two groups were 53.2% (95% CI 38.7-67.7) and 28.0% (95% CI 13.6-42.3), respectively.

In terms of OS, the median OS for the CHOPX group has not yet been reached, while the median OS for the CHOP group was 30.9 months. The CHOPX group showed a trend toward improved OS, but the current statistical results are not significant (HR 0.55, 95% CI 0.28-1.10; P=0.088). The 2-year OS rates for the two groups were 68.0% and 60.8%, respectively.

Regarding safety, neutropenia was the most common adverse event in both the CHOPX and CHOP groups (82% in the CHOPX group and 73% in the CHOP group). The most common grade 3-4 hematologic adverse event in both groups was neutropenia, and the most common grade 3-4 non-hematologic adverse event was infection. In the CHOPX group, 65% (31 patients) reported neutropenia, but no patients experienced prolonged neutropenia (>14 days) or required dose adjustments of the targeted drugs, and 10% (5 patients) experienced infections. In the CHOP group, these proportions were 52% (25 patients) and 4% (2 patients), respectively.

In conclusion, the study results indicate that different targeted drugs combined with CHOP demonstrate good efficacy and safety. These findings provide preliminary evidence supporting the use of CHOPX as a first-line treatment for PTCL patients with different genetic mutations, and suggest that biomarker-driven treatment strategies are feasible and worth further exploration in the future.