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INTRATHECAL METHOTREXATE PROPHYLAXIS AND CENTRAL NERVOUS SYSTEM RELAPSE IN PATIENTS WITH DIFFUSE LARGE B-CELL LYMPHOMA TREATED WITH INTENSIFIED R-ACVBP STRATEGY
Author(s): ,
Loïc Renaud
Affiliations:
Hemato-oncologie, DMU DHI ; Université de Paris,AP-HP, Hôpital Saint-Louis, F-75010 Paris,France;Hemato-oncologie, DMU DHI ; Université de Paris,AP-HP, Hôpital Saint-Louis, F-75010 Paris,Frankreich;Hemato-oncologie, DMU DHI ; Université de Paris,AP-HP, Hôpital Saint-Louis, F-75010 Paris,Francia;Hemato-oncologie, DMU DHI ; Université de Paris,AP-HP, Hôpital Saint-Louis, F-75010 Paris,France;Hemato-
,
Pierre Stéphan
Affiliations:
Department of Hematology,University Hospital F. Mitterrand and Inserm UMR 1231,Dijon,France;Department of Hematology,University Hospital F. Mitterrand and Inserm UMR 1231,Dijon,Frankreich;Department of Hematology,University Hospital F. Mitterrand and Inserm UMR 1231,Dijon,Francia;Department of Hematology,University Hospital F. Mitterrand and Inserm UMR 1231,Dijon,France;Department of Hematology,Un
,
sixte durand
Affiliations:
Department of Hematology,Centre Henri Becquerel, University of Rouen,Rouen,France;Department of Hematology,Centre Henri Becquerel, University of Rouen,Rouen,Frankreich;Department of Hematology,Centre Henri Becquerel, University of Rouen,Rouen,Francia;Department of Hematology,Centre Henri Becquerel, University of Rouen,Rouen,France;Department of Hematology,Centre Henri Becquerel, University of Roue
,
Guillaume Escure
Affiliations:
Department of Hematology,CHU Lille, Université de Lille 2, ,Lille,France;Department of Hematology,CHU Lille, Université de Lille 2, ,Lille,Frankreich;Department of Hematology,CHU Lille, Université de Lille 2, ,Lille,Francia;Department of Hematology,CHU Lille, Université de Lille 2, ,Lille,France;Department of Hematology,CHU Lille, Université de Lille 2, ,Lille,Francia;Department of Hematology,CHU
,
morschhauser Franck
Affiliations:
Department of Hematology,CHU Lille, Unité GRITA, Université de Lille 2,Lille,France;Department of Hematology,CHU Lille, Unité GRITA, Université de Lille 2,Lille,Frankreich;Department of Hematology,CHU Lille, Unité GRITA, Université de Lille 2,Lille,Francia;Department of Hematology,CHU Lille, Unité GRITA, Université de Lille 2,Lille,France;Department of Hematology,CHU Lille, Unité GRITA, Université
,
vincent camus
Affiliations:
Department of Hematology,Centre Henri Becquerel, University of Rouen,Rouen,France;Department of Hematology,Centre Henri Becquerel, University of Rouen,Rouen,Frankreich;Department of Hematology,Centre Henri Becquerel, University of Rouen,Rouen,Francia;Department of Hematology,Centre Henri Becquerel, University of Rouen,Rouen,France;Department of Hematology,Centre Henri Becquerel, University of Roue
,
Hervé tilly
Affiliations:
Department of Hematology,Centre Henri Becquerel, University of Rouen,Rouen,France;Department of Hematology,Centre Henri Becquerel, University of Rouen,Rouen,Frankreich;Department of Hematology,Centre Henri Becquerel, University of Rouen,Rouen,Francia;Department of Hematology,Centre Henri Becquerel, University of Rouen,Rouen,France;Department of Hematology,Centre Henri Becquerel, University of Roue
,
Olivier casasnovas
Affiliations:
Department of Hematology,University Hospital F. Mitterrand and Inserm UMR 1231,Dijon,France;Department of Hematology,University Hospital F. Mitterrand and Inserm UMR 1231,Dijon,Frankreich;Department of Hematology,University Hospital F. Mitterrand and Inserm UMR 1231,Dijon,Francia;Department of Hematology,University Hospital F. Mitterrand and Inserm UMR 1231,Dijon,France;Department of Hematology,Un
,
Sylvie Chevret
Affiliations:
Biostatistiques,AP-HP, Hôpital Saint-Louis,Université de Paris – Paris Diderot ,paris,France;Biostatistiques,AP-HP, Hôpital Saint-Louis,Université de Paris – Paris Diderot ,paris,Frankreich;Biostatistiques,AP-HP, Hôpital Saint-Louis,Université de Paris – Paris Diderot ,paris,Francia;Biostatistiques,AP-HP, Hôpital Saint-Louis,Université de Paris – Paris Diderot ,paris,France;Biostatistiques,AP-HP,
Catherine Thieblemont
Affiliations:
Hemato-oncologie, DMU DHI ; Université de Paris,AP-HP, Hôpital Saint-Louis,F-75010 Paris,France;Hemato-oncologie, DMU DHI ; Université de Paris,AP-HP, Hôpital Saint-Louis,F-75010 Paris,Frankreich;Hemato-oncologie, DMU DHI ; Université de Paris,AP-HP, Hôpital Saint-Louis,F-75010 Paris,Francia;Hemato-oncologie, DMU DHI ; Université de Paris,AP-HP, Hôpital Saint-Louis,F-75010 Paris,France;Hemato-onco
(Abstract release date: 05/12/22) EHA Library. Renaud L. 06/10/22; 358076; P1217
Loïc Renaud
Loïc Renaud
Contributions
Abstract
Presentation during EHA2022: All (e)Poster presentations will be made available as of Friday, June 10, 2022 (09:00 CEST) and will be accessible for on-demand viewing until Monday, August 15, 2022 on the Congress platform.

Abstract: P1217

Type: Poster presentation

Session title: Aggressive Non-Hodgkin lymphoma - Clinical

Background

Central nervous system (CNS) relapse of diffuse large B-cell lymphoma is relatively uncommon (2-5%) and remains catastrophic with a median survival of 2 to 5 months. Intrathecal (IT) or intravenous high-dose methotrexate (HD MTX) have limited if any prophylactic impact on CNS relapse. We recently demonstrated in a cohort of 2203 patients included in multicenter clinical trials conducted by LYSA and GLA/ DSHNHL, that only 4 (1.6%) CNS relapses were seen with the R-ACVBP strategy in pts with aaIPI 2, 3 (and intermediate/high CNS-IPI), while 15 (3.9%) relapses did occur after R-(Mega)CHO(E)P. 

Aims
To address the role of IT in this intensified strategy R-ACVBP, we took the advantage of real world data of patients treated in four centers, and compared CNS relapses occurring in patients treated with R-ACVBP strategy with or without IT.

Methods
The LYSA R-ACVBP strategy include four cycles of R-ACVBP (75 mg/m² doxorubicin, and 1200 mg/m² cyclophosphamide; 2 mg/m² vindesine and 10 mg bleomycin on days 1 and 5) with four IT, two cycles of high dose methotrexate (3g/m²), four cycles of R-etoposide (300 mg/m²) and ifosfamide (1500 mg/m²) and 2 cycles of cytarabine(100 mg/m²) given sub cutaneously for 4 days. 233 patients with previously untreated diffuse large B-cell lymphoma (DLBCL) aged 18 to 59 years old received this intensified strategy between 2010 and 2020.  We excluded 30 patients who received ASCT in first line and 10 others who received less than four cycles of R-ACVBP. We assessed the risk for of relapse and CNS-relapse. We also assesed the impact of the 2 courses of subcutaneous aracytine on overall survival (OS) and progression free survival (PFS).

Results

A total of 193 pts were included. Median age was 44.4 years (IQR, 30.8-53, range: 17-62). Distribution of CNS IPI was not significantly different comparing IT (n=132) vs non-IT (n=61) groups within aaIPI categories (Table 1). 92 patients did not receive the two courses of subcutaneous Aracytine (no AraC group) for consolidation and 101 patients received the two courses (AraC group).

With a median follow-up at 57.2 months, the 3 year OS and 3 year PFS of the whole cohort was 93.6% and 86.2%, respectively, without significant difference between IT and non IT groups in terms of OS (3yr-OS,  = 92.3% versus 95.1%, HR= 1.29 (95%CI, 0.41 to 4.04, p=0.67) and PFS (3yr-PFS,  84.4% versus 90.1%, HR= 1.26 (95%CI, 0.59 to 2.72, p=0.55).

The 3y-cumulative incidence of CNS relapse for pts treated IT group was 3.2% (95%CI, 1.0 to 7.4), and 3.3% (95%CI, 0.6 to 10.2) in the non-IT group (p= 0.93). In pts with aaIPI 1, two patients experienced a CNS relapse, one in the IT group and one in the non-IT group. In pts with aaIPI 2,3 and intermediate/high CNS IPI, 4 patients experienced a CNS relapse, three out of four in the IT group.

92 patients did not receive the two courses of subcutaneous Aracytine (no AraC group) for consolidation and 101 patients received the two courses (AraC group). Receiving or not AraC did not have any impact on the CNS relapse with a risk of CNS relapse at 4.1% (95%CI, 1.3 to 9.5) for patients receiving AraC and 2.2% (95%CI, 0.4 to 6.9) for patients not receiving AraC (p= 0.48).

Conclusion

CNS relapse was rare in younger DLBCL treated with this intensified strategy. Only 6 CNS relapses were observed without difference between IT and non-IT groups. The results presented at the EHA will included the total cohort of more than 600 patients.

Keyword(s): DLBCL, Methotrexate, Prophylaxis

Presentation during EHA2022: All (e)Poster presentations will be made available as of Friday, June 10, 2022 (09:00 CEST) and will be accessible for on-demand viewing until Monday, August 15, 2022 on the Congress platform.

Abstract: P1217

Type: Poster presentation

Session title: Aggressive Non-Hodgkin lymphoma - Clinical

Background

Central nervous system (CNS) relapse of diffuse large B-cell lymphoma is relatively uncommon (2-5%) and remains catastrophic with a median survival of 2 to 5 months. Intrathecal (IT) or intravenous high-dose methotrexate (HD MTX) have limited if any prophylactic impact on CNS relapse. We recently demonstrated in a cohort of 2203 patients included in multicenter clinical trials conducted by LYSA and GLA/ DSHNHL, that only 4 (1.6%) CNS relapses were seen with the R-ACVBP strategy in pts with aaIPI 2, 3 (and intermediate/high CNS-IPI), while 15 (3.9%) relapses did occur after R-(Mega)CHO(E)P. 

Aims
To address the role of IT in this intensified strategy R-ACVBP, we took the advantage of real world data of patients treated in four centers, and compared CNS relapses occurring in patients treated with R-ACVBP strategy with or without IT.

Methods
The LYSA R-ACVBP strategy include four cycles of R-ACVBP (75 mg/m² doxorubicin, and 1200 mg/m² cyclophosphamide; 2 mg/m² vindesine and 10 mg bleomycin on days 1 and 5) with four IT, two cycles of high dose methotrexate (3g/m²), four cycles of R-etoposide (300 mg/m²) and ifosfamide (1500 mg/m²) and 2 cycles of cytarabine(100 mg/m²) given sub cutaneously for 4 days. 233 patients with previously untreated diffuse large B-cell lymphoma (DLBCL) aged 18 to 59 years old received this intensified strategy between 2010 and 2020.  We excluded 30 patients who received ASCT in first line and 10 others who received less than four cycles of R-ACVBP. We assessed the risk for of relapse and CNS-relapse. We also assesed the impact of the 2 courses of subcutaneous aracytine on overall survival (OS) and progression free survival (PFS).

Results

A total of 193 pts were included. Median age was 44.4 years (IQR, 30.8-53, range: 17-62). Distribution of CNS IPI was not significantly different comparing IT (n=132) vs non-IT (n=61) groups within aaIPI categories (Table 1). 92 patients did not receive the two courses of subcutaneous Aracytine (no AraC group) for consolidation and 101 patients received the two courses (AraC group).

With a median follow-up at 57.2 months, the 3 year OS and 3 year PFS of the whole cohort was 93.6% and 86.2%, respectively, without significant difference between IT and non IT groups in terms of OS (3yr-OS,  = 92.3% versus 95.1%, HR= 1.29 (95%CI, 0.41 to 4.04, p=0.67) and PFS (3yr-PFS,  84.4% versus 90.1%, HR= 1.26 (95%CI, 0.59 to 2.72, p=0.55).

The 3y-cumulative incidence of CNS relapse for pts treated IT group was 3.2% (95%CI, 1.0 to 7.4), and 3.3% (95%CI, 0.6 to 10.2) in the non-IT group (p= 0.93). In pts with aaIPI 1, two patients experienced a CNS relapse, one in the IT group and one in the non-IT group. In pts with aaIPI 2,3 and intermediate/high CNS IPI, 4 patients experienced a CNS relapse, three out of four in the IT group.

92 patients did not receive the two courses of subcutaneous Aracytine (no AraC group) for consolidation and 101 patients received the two courses (AraC group). Receiving or not AraC did not have any impact on the CNS relapse with a risk of CNS relapse at 4.1% (95%CI, 1.3 to 9.5) for patients receiving AraC and 2.2% (95%CI, 0.4 to 6.9) for patients not receiving AraC (p= 0.48).

Conclusion

CNS relapse was rare in younger DLBCL treated with this intensified strategy. Only 6 CNS relapses were observed without difference between IT and non-IT groups. The results presented at the EHA will included the total cohort of more than 600 patients.

Keyword(s): DLBCL, Methotrexate, Prophylaxis

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