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2712 Consolidation Radiotherapy Improved Survival in Limited Stage Diffuse Large B-Cell Lymphoma (DLBCL): A Nationwide Multi-Institutional Registry of 816 Cases in Thailand

Lymphoma: Chemotherapy, excluding Pre-Clinical Models
Program: Oral and Poster Abstracts
Session: 623. Lymphoma: Chemotherapy, excluding Pre-Clinical Models: Poster II
Sunday, December 6, 2015, 6:00 PM-8:00 PM
Hall A, Level 2 (Orange County Convention Center)

Lalita Norasetthada, MD1, Weerasak Nawarawong, MD2, Arnuparp Lekhakula, MD, MS3*, Jakrawadee Julamanee, MD3*, Chittima Sirijerachai, MD4*, Kanchana Chansung, MD4*, Kitsada Wudhikarn, MD5*, Udomsak Bunworasate, MD6*, Noppadol Siritanaratanakul, MD7, Archrob Khuhapinant, MD, PhD7, Tontanai Numbenjapon, MD8*, Kannadit Prayongratana, MD8*, Tawatchai Suwanban, MD9*, Suporn Chuncharunee, MD10, Pimjai Niparuck, MD10*, Somchai Wongkhantee, MD11*, Peerapon Wong, MD12*, Nisa Makruasi, MD13*, Nonglak Kanitsap, MD14* and Tanin Intragumtornchai, MD, MSc5

1Maharaj Nakorn Chiang Mai Hospital, Chiang Mai, Thailand
2Department of Medicine, Chiang Mai University, Chiang Mai, Thailand
3Department of Internal Medicine, Prince of Songkla University, Songkla, Thailand
4Department of Medicine, Khon Kaen University, Khon Kaen, Thailand
5Department of Internal Medicine, Chulalongkorn University, Bangkok, Thailand
6Department of Medicine, Chulalongkorn University, Bangkok, Thailand
7Department of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
8Department of Medicine, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand
9Department of Medicine, Rajavithi Hospital, Bangkok, Thailand
10Department of Internal Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
11Department of Medicine, Khonkaen Regional Hospital, Khon Kaen, Thailand
12Department of Medicine, Naresuan University, Phitsanulok, Thailand
13Department of Medicine, Srinakharinwirot University, Nakhon Nayok, Thailand
14Department of Medicine, Thammasat University, Bangkok, Thailand

Introduction

The additional benefit of consolidation radiotherapy (RT) following chemotherapy in limited stage DLBCL remains controversial. Previous 5 randomized trials, 4 trials before rituximab era (SWOG 8736, ECOG 1484, GELA 93-1 and 93-4 studies) and 1 trial with R-CHOP combination (Lysa/Goelams 02-03), could not demonstrate a remarkable benefit of RT. The purpose of this study is to explore the benefit of combined modality treatment including the combination of RT and rituximab (R)-based chemotherapy in limited stage DLBCL. 

Methods

From the 4,371 patients in a multi-institutional registry of newly diagnosed lymphoma in Thailand between 2007-2014, there were a total of 2,399 patients with DLBCL. We included patients with limited stage DLBCL receiving CHOP/CHOP-liked chemotherapy +/- R and +/- RT. The baseline patient characteristics and clinical outcomes were analyzed according to treatment modalities.

Results

A total of 816 patients with a median age of 56 years (range, 15-91) were included in the study. Male:female was 1:1.1. Majority of patients had primary extranodal diseases (58%), stage II (68%), good performance status (89%), normal LDH (55%) and no B-symptoms (59%). The IPI scores were 0 (30.6%), 1(45%), 2 (20%) and 3 (3.9%), respectively. The modalities of treatment were CHOP alone (48.5%), R-CHOP (26.5%), CHOP+RT (17.9%) and R-CHOP+RT (7.1%). Patients in R-CHOP group were older than in other groups (P=0.001) (Table 1). There was a higher proportion of patients in stage II disease in R-CHOP (74.1%) and R-CHOP+RT (74.1%) groups than in CHOP (66.9%) and CHOP+RT (57.5%) groups (P =0.007), whereas the patients were relatively equally distributed between the IPI scores. Complete response (CR) rate was higher in R-CHOP+RT group (82.8%) than in R-CHOP (75%), CHOP+RT (70%) and CHOP groups (58%) (P <0.001). CR was independently associated with consolidation RT (OR 0.65, 95%CI: 0.45-0.97), rituximab-based therapy (OR 0.66; 95%CI: 0.55-0.79) and IPI score (OR 1.90; 95%CI: 1.41-2.57). With a median follow up of 52 months, 4-year progression free survival (PFS) were 76.4%, 69.4%, 61.4% and 49.9% in R-CHOP+RT, R-CHOP, CHOP+RT and CHOP alone, respectively, (P <0.001) (Figure. 1). The corresponding figures of 4-year OS for each group were 78.6%, 76.3%, 64.3% and 59.6%, respectively (P<0.001) (Figure. 2). Multivariate analysis showed that factors associated with survivals were consolidation RT (HR for PFS 0.63, 95%CI: 0.48-0.82; HR for OS 0.70, 95%CI: 0.53-0.94), rituximab-based therapy (HR for PFS 0.72, 95%CI: 0.64-0.83; HR for OS 0.69, 95%CI: 0.60-0.81) and IPI scores (HR for PFS 1.87, 95%CI: 1.54-2.26; HR for OS 1.96, 95%CI: 1.60-2.41)

Conclusion

In limited stage DLBCL, consolidation RT plus R-CHOP yielded a superior outcome compared to R-CHOP, CHOP + RT and CHOP alone. Thus, RT continues to have an important role and should not be omitted in management of limited stage DLBCL in rituximab era.

 

Clinical characteristics

CHOP alone

(n= 396)

CHOP + RT

(n = 146)

R-CHOP alone

(n = 216)

R-CHOP + RT

(n = 58)

p-value

Male

 

211 (53%)

75(51.4%)

125 (57.9%)

24 (41.4%)

0.14

Median age (years)

56 (15-90)

52 (15-86)

60 (17-91)

55 (15-81)

0.001

Age ≥ 60

155 (39.1%)

51 (34.9%)

109 (50.5%)

20 (34.5%)

0.008

Primary extranodal disease

226 (57.1%

79 (54.1%)

136 (63.0%

34 (58.6%)

0.35

Stage

  Stage I

  Stage II

131 (33.1%)

269 (66.9%)

62 (42.5%)

84 (57.5%)

56 (25.9%)

160 (74.1)

15 (25.9%)

43 (74.1%)

0.007

B-symptom

116 (32.6%)

47 (36.2%)

58 (31.4%)

13 (28.9%)

0.76

HIV seropositivity

15 (4.6%)

9 (7.0%)

-

-

0.004

High serum LDH

173 (43.7%)

74 (50.7%)

95 (44.0%)

26 (44.8%)

0.51

ECOG ≥ 2

31 (7.8%)

22 (15.1%)

25 (11.6%)

7 (12.1%)

0.08

IPI

  Low (IPI =0-1)

  Low-intermediate (IPI =2)

  High-intermediate (IPI = 3)

312 (78.8%)

75 (18.9%)

9 (2.3%)

107(73.3%)

32 (29.1%)

7 (4.8%)

157 (72.7%)

48 (22.2%)

11 (5.1%)

46 (79.3%)

9 (15.5%)

3 (5.2%)

 

0.35

Response

  Overall response

  Complete response

258 (65.2%)

230 (58.1%)

116(79.4%)

103(70.5%)

179 (82.9%)

162 (75%)

51 (88%)

48 (82.8%)

 

<.0001

Table 1. Comparison of characteristics of patients according to treatment modalities

Screen%20Shot%202558-07-29%20at%209.30.16%20PM.png

Figure 1. The Kaplan-Meier plots of PFS according to treatment groups

Screen%20Shot%202558-07-29%20at%209.31.17%20PM.png

Figure 2. The Kaplan-Meier plots of OS according to treatment groups

 

Disclosures: Khuhapinant: Roche: Honoraria .

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