Therapeutic results of diffuse large B-Cell lymphoma

N.Ait Amer; F.Tensaout; H.Moussaoui; F.Belhadri; N.Abdennebi; F.Boukhamia; D.Benali; L.Metidji;

S.Zeghouati; S.Zerkout; N.Boudjerra;R.M.Hamladji;

Service d’Hématologie- Greffe de moelle osseuse Centre Pierre et Marie Curie

Introduction Diffuse large B-Cell lymphoma (LDGCB) represents approximately 40% of all lymphomas and 80% of aggressive lymphomas

According to the Ann Arbor classification, the localized stage (clinical stages I/II) represent 35% to 45% of cases and advanced stage (clinical stages III/IV) 55% to 65% of cases(Hématologie

2007;13(5):320-3).

The possibility of treating patients is based on a very precise stading of the disease and a deep investigation of the individual pronostic factors.

Materials and Methods (1)

Between the 228 patients (pts) diagnosed as LDGCB from January 2001 to december 2010; we report the out come of 196 pts treated by CHOP with the advent of Rituximab (R) or not; followed or not by radiotherapy as first line treatment.

Are excluded from the study all the cerebral lymphomas, the primary mediastinal lymphomas and the bones lymphomas.

For the 196 pts of this study: -The median age is 57 years (16-83)-The sex ratio= 1,3 (111M/85F)-The median time to diagnosis : 5 months (0-48)

Materials and Methods (2)Clinical Staging:

Stages Number %

I 26 1396 (49%)

II 70 36

III 55 28100 (51%)

IV 45 23

Bulky disease

(large tumour size ≥ 7 cm)

Localized stages(96) 37 39

Advanced stages (100) 48 48

Materials and Methods (3)

International pronostic index: has been determined in only 149/196 pts

IPI Number %

Low risk56 38 Good

pronostic (67%)Low-intermediate

risk 44 29

High intermediate risk 38 26

Poor pronostic (33%)High risk

11 7

Materials and Methods (4)

• The CHOP regimen is the combination of 750 mg/m² of Cyclophosphamide on day 1; 50 mg/m² of doxorubicin on day 1; 1,4 mg/m² of vincristine, up to a maximal dose of 2 mg on day 1; and 40 mg/m² of prednisone per day for five days.

• Advent or not Rituximab at a dose of 375 mg/m² on the day one of each CHOP cycle; with an average of 4 cycles of CHOP (1-8); every 3 weeks.

• The radiotherapy was given on the lymph-node regions involved at a dose of 40 Gy.

• At december 2011, the median follow up is 60 months (12 at 132)

Therapy (1)

• Advanced stage: 100 pts - 59 pts received CHOP olone- 41 pts received R-CHOP- 28 pts among them; who are in first response after the

first line therapy (CHOP ± R) underwent intensive regimens (27 pts have a high dose therapy followed by autologous stem cell transplantation [ASCT]; and 1 pt has an allogenic stem cell transplantation with a previous reduce conditionning regimen).

• Localized stage : 96 pts- 58 pts received CHOP ± R+RT - 38 pts received CHOP ± R (6pts underwent ASCT)

Materials and Methods (5)Therapy (2)

Results (1)Advanced Stage: 100 pts First results :

CHOP (59pts) R-CHOP (41pts) P

CR 35 (59%) 17 (42%) P=1,63 NS

RP 05 (09%) 12 (29%) /

Overall remission 40 (68%) 29 (71%) P=0,76 NS

Failures 10 (17%) 10 (24%) /

Dead related to treatment Toxicity (TRM)

09 (15%) 02 (05%) /

Results(2)Advanced stage 72/100 pts (28pts have been intensified ) Out come of their response

CHOP (29pts) R-CHOP (12pts)

Persistant response 08 (28%) 03 (25%)

Relapse 13 (45%) 05 (42%)

Death (CR) 02 (07%) 04 (33%)

Losing sight pts (CR) 06 (20%) /

Results (3)Out come of the advanced stage: 72 Pts

Alives CHOP : 12 (25%) R-CHOP: 08 (33%)

Death CHOP: 30(63%) R-CHOP: 16(66%) Losing

sight pts

CHOP 48pts

1st CR 2nd CRRelapse Failure

1st CR

Relapse failure Toxicity

0608 02 02 02 11 08 09

R-CHOP 24pts 03 04 01 04 01 09 02

EFS

Advanced stage

[0-12[ [12-24[ [24-36[ [36-48[ [48-60[ [60-72[ [72-84[ [84-96[ [96-108[ [108-120[

[120-132[

0%

5%

10%

15%

20%

25%

30%

35%

40%

R-CHOP 0,5< P <0,3

CHOP

CHOP+R-CHOP

%

26%

14%

22%

OSAdvanced stage

[0-12[ [12-24[ [24-36[ [36-48[ [48-60[ [60-72[ [72-84[ [84-96[ [96-108[ [108-120[

[120-132[

0%

10%

20%

30%

40%

50%

60%

R-CHOP 0,5< P <0,3 NS

CHOP

CHOP+R-CHOP

%

31%

30%

18%

Results (4) Localized stage : 96 pts

First results CHOP± R+RT (58pts)

After CT After RTCHOP± R

(38pts) P

CR 40 (69%) 56 (97%) 20 (53%) P ˂ 10-5 S

PR 18 (31%) 02 (03%) 03 (07%) /

Overall response 58 (100%) 23 (60%) P ˂ 10-5 S

Failure / 09 (24%) /

TRM / 06 (16%) /

Results (5)Localized stage: 90/96 pts (6pts have been intensified) The out come of response:

Réponse Alives in CR Relapse Death Lost in sight pts

CHOP ± R+ RT (58 pts) 36 (62%) 14 (24%) 03 CR (05%) 05 CR (09%)

CHOP ± R(17/32 pts) 11 (65%) 04 (24%) 02 CR (11%)

Results (6)Out come of the localized stage : 90 pts

Alives CHOP ± R +RT : 39 (67%) CHOP ± R : 13 (41%)

Death CHOP ± R +RT: 14(24%) CHOP ± R: 17 (53%) Losing

sight pts

CHOP ± R +RT (58pts)

1st CR

2nd CR Relapse Failure

1st CR

Relapse failure Toxicity

36 (62%) 03 / 03 11 / / 05

CHOP ± R (32pts)

11 (65%) 01 01 / 03 08 06 02

EFS Localized stage

[0-12[ [12-24[ [24-36[ [36-48[ [48-60[ [60-72[ [72-84[ [84-96[ [96-108[ [108-120[

[120-132[

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

CHOP±R+RT 0,01< P <0,02 S

CHOP±R

CHOP±R / CHOP±R+RT

50%45%

36%

OSLocalized stage

[0-12[ [12-24[ [24-36[ [36-48[ [48-60[ [60-72[ [72-84[ [84-96[ [96-108[ [108-120[

[120-132[

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

CHOP±R+RT 0,001< P <0,01 S

CHOP±R

CHOP±R / CHOP±R+RT

36%

66%

55%

Results (7)Out come of • ASCT: 33pts• Allogeneic SCT: 01 pt alives in CR at 9 months follow up.

ASCT Number %

Status before the transplant(33pts)

CR 22 66

PR 11 34

status after transplant(33pts)

CR 29 88

TRM 04 12

Out come of CR (29 pts)

Alives in CR 21 72

Relapse 06 (5 Death- 1 alive in CR 2) 21

Death in CR 02 07

EFSCT/ASCT

OSCT/ASCT

Conclusion

The characteristics of the series :• Median age 57 years(young/literature)• Advanced stages= localized stages• Bulky forms represent 48%of the advanced stages• Good pronostic groupe represent67%/poor pronostic groupe 33%

In the localized forms:• The radiotherapy increased survival regardless of previous treatment CHOP with or

without R (OS at 10 years 66% vs 36%)

In advanced forms:• ASCT increased survival significantly(OS at 10 years 56% vs 31%)• Our results do not reach the literature because of the bulky forms with the

percentage is important in this population:may be should we practice a more intensive therapy(ACVBP regimen)?