Ten-year Outcomes of Standard CHOP Chemotherapy Regimen to CHOP Plus Rituximab in Patients with Diffuse large B-cell Lymphoma

27 Jan, 22

Introduction

LNH-98.5 trial was the first randomized study comparing the standard CHOP chemotherapy regimen to CHOP plus rituximab (R-CHOP) performed by Groupe d’Etudes des Lymphomes de l’Adulte (GELA). The 2-year results demonstrated that the addition of rituximab to the CHOP regimen resulted in favorable outcomes in elderly patients with diffuse large B-cell lymphoma (DLBCL), with a greater proportion of complete responders and longer event-free and overall survival compared with CHOP alone.

Aim

To compare long term outcomes of the standard CHOP chemotherapy regimen to CHOP plus rituximab (R-CHOP) in elderly patients with DLBCL

Patient Profile

Patients with DLBCL aged 60 to 80 years
Previously untreated DLBCL according to the World Health Organization classification, stage II, III, or IV disease, and performance status (PS) 0 to 2 according to the Eastern Clinical Oncology Group (ECOG) scale

Methods

Patients were randomized to treatment with either standard CHOP therapy or CHOP plus rituximab

Study Drugs

CHOP: Patients treated with CHOP received 750 mg/m² cyclophosphamide, 50 mg/m² doxorubicin, 1.4 mg/m² vincristine up to a maximum dose of 2 mg on day 1, and 40 mg/m²/day prednisone on days 1 to 5, for each treatment cycle
R-CHOP: Patients treated with R-CHOP received rituximab at a dose of 375 mg/m² on day 1 of each of the 8 cycles along with CHOP regimen

Median Follow-up Duration: 10 years

Study Endpoints

The primary efficacy parameter was event-free survival (EFS). Events were defined as the following: disease progression or relapse, initiation of a new (unplanned) anticancer treatment (e.g., radiation therapy), or death from any cause without progression
Secondary efficacy end points included overall survival (OS), progression-free survival (PFS), disease-free survival (DFS), response rates, and toxicity

Results

The addition of rituximab improved PFS and OS rates in this patient population, with an overall increase of 16% versus CHOP alone.

Figure 1: Survival Endpoints

Table1: Number of events observed in the CHOP and R-CHOP arms after a 10-year median follow-up period

Type of event	CHOP	R-CHOP
PD during treatment	44 (22.3%)	19 (9.4%)
New unplanned treatment	9 (4.6%)	11 (5.4%)
Progression after stable disease	1 (0.5%)	1 (0.5%)
PD after partial response	5(2.5%)	6 (3.0%)
Relapse for CR patients	71 (36.0%)	49 (24.3%)
Death without PD during treatment	12 (6.1%)	12 (5.9%)
Death without PD after treatment	16 (8.1%)	33 (16.3%)
No event	39 (19.8%)	71 (35.1%)

CHOP: cyclophosphamide, doxorubicin, vincristine, and prednisone; R-CHOP: rituximab-CHOP; PD: progressive disease; and CR: complete response

The median OS after progression was 0.6 and 0.7 months for the CHOP and R-CHOP arms, respectively
Median DFS was 3.4 years in the CHOP arm and was not yet reached in the R-CHOP arm (P <.0001)
Some patients responded well to salvage therapy and had a relatively long survival period after progression
- The 5- and 10-year survival after progression were 14.6% and 10.5% in the CHOP arm, compared with 25.0% and 8.6% in the R-CHOP arm, respectively

Overall, the number of patients exhibiting late disease progression was low, but there was a trend toward a better outcome for those patients treated with R-CHOP compared with those treated with CHOP alone

Table 2. Outcome of patients with PD according to time of progression and initial treatment arm

PD	Median survival (y)	2-year survival (%)	3-year survival (%)	5-year survival (%)
PD within the first 3 years
CHOP	0.6	25.9	19.6	14.3
R-CHOP	0.6	18.2	18.2	16.7
PD between years 4 and 5
CHOP	3.0	83.3	50.0	16.7
R-CHOP	not reached	83.3	66.7	66.7
PD after 5 years
CHOP	0.9	22.2	22.2	22.2
R-CHOP	not reached	87.5	87.5	58.3

PD: progressive disease; CHOP: cyclophosphamide, doxorubicin, vincristine, and prednisone; and R-CHOP: rituximab-CHOP.

The same risk of death due to other diseases, secondary cancers, and late relapses was observed in both study arms
Relapses occurring after 5 years represented 7% of all disease progressions

Conclusion

The addition of rituximab improved PFS and OS rates in this patient population, with an overall increase of 16% versus CHOP alone
The patient cohort chosen for this trial was elderly DLBCL patients (60-80 years of age), a particularly challenging group to manage and treat
With the improvements in PFS and OS rates from the addition of rituximab to standard treatment regimens, a significant proportion of elderly patients experience long-term survival
The 10-year analysis confirmed the benefits and tolerability of the addition of rituximab to CHOP
Late relapses can be expected in DLBCL patients if the follow-up period is sufficiently long
The risk of death due to other diseases or secondary cancers was not higher in the R-CHOP group
These findings confirm that the use of R-CHOP can improve patient outcomes in elderly DLBCL patients, and that the beneficial effects are sustained over a long follow-up period

Reference

Blood. 2010; 116(12):2040-2045