A PREDICTIVE SCORE FOR CNS DISSEMINATION AND ITS EFFECT ON CNS PROPHYLAXIS IN A MONO-INSTITUTIONAL SERIES OF 242 PATIENTS WITH DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL) TREATED IN THE RITUXIMAB ERA
(Abstract release date: 05/19/16)
EHA Library. Ferreri A. 06/09/16; 132512; E963
Dr. Andres Jose Maria Ferreri
Contributions
Contributions
Abstract
Abstract: E963
Type: Eposter Presentation
Background
CNS dissemination is a lethal event in DLBCL. Early detection and effective CNS prophylaxis may reduce related mortality. However, risk predictors reported in the rituximab era exhibits a low diagnostic sensitivity and the most effective prophylaxis remains to be defined.
Aims
We analysed these two unmet clinical needs in a retrospective series of 242 pts with DLBCL treated in the rituximab era.
Methods
Consecutive HIV-neg adults with DLBCL without CNS involvement treated with R-CHOP or similar were considered. CNS, mediastinal and leg-type DLBCL, high-grade transformed lymphomas and pts registered in prospective trials were excluded. Following institutional guidelines, no DLBCL pt diagnosed before 2007 received CNS prophylaxis; after 2007, CNS prophylaxis, consisting of 3-4 cycles of methotrexate 3 g/m2 ± intrathecal liposomal cytarabine (IT) was indicated in pts with high CNS recurrence risk. IT was delivered one dose per R-CHOP course, and methotrexate was delivered after R-CHOP treatment. CNS dissemination risk was defined by involvement of the testis, kidney/adrenal, spine, skull, paranasal sinuses, orbit, and/or breast or by the simultaneous presence of advanced stage and high serum LDH. In the present study, CNS dissemination risk was defined as low in pts without involvement of high-risk extranodal organs and with an International Prognostic Index (IPI) of 0-3; intermediate in pts without involvement of high-risk extranodal organs and with an IPI of 4-5; and high in pts with involvement of above-mentioned high-risk extranodal organs and with any IPI.
Results
242 pts were analysed (median age 66, range 18-89). According to the proposed model, CNS dissemination risk was low in 148 (61%) pts, intermediate in 29 (12%) and high in 65 (27%). Pts with low and intermediate risk were managed without prophylaxis, whereas this strategy was indicated in 45 high-risk pts: 35 pts received intravenous ± IT chemotherapy, 10 pts receive only IT chemotherapy due to MTHFR polymorphisms, comorbidity or old age. CNS prophylaxis was well tolerated; unexpected toxicity and interruptions due to toxicity were not recorded.At a median follow-up of 51 months (12-171), 11 (4.5%) pts experienced CNS relapse: in the brain parenchyma in 6 cases, in the meninges in the others. CNS relapse rate was <1% (1/148) in low-risk pts, 10% (3/29) in intermediate-risk, and 11% (7/65) in high-risk pts. Eight of these pts died of CNS progressive lymphoma after 7-37 months (median 12).In the high-risk subgroup, CNS relapse rate was 25% (5/20) in pts who did not receive CNS prophylaxis, 20% (2/10) in pts treated IT chemotherapy alone and 0% (0/35) in pts who received intravenous ± IT chemotherapy (p=0.004). Overall, 18 high-risk pts experienced relapse, and CNS was the most commonly involved site (7/18). Moreover, the addition of intravenous CNS prophylaxis was associated with a significantly improved PFS (3-yr: 80% vs. 42%; p=0.001) and OS (3-yr: 86% vs. 43%; p=0.00007).
Conclusion
With all the limitations of a retrospective series, this study suggest that pts with DLBCL and involvement of certain extranodal organs and/or high IPI should receive CNS prophylaxis with intravenous high-dose methotrexate and IT liposomal cytarabine. This strategy shows a relevant effect on survival of high-risk pts as CNS is a common relapse site, associated with a high mortality.
Session topic: E-poster
Keyword(s): CNS lymphoma, Diffuse large B cell lymphoma, Prophylaxis
Type: Eposter Presentation
Background
CNS dissemination is a lethal event in DLBCL. Early detection and effective CNS prophylaxis may reduce related mortality. However, risk predictors reported in the rituximab era exhibits a low diagnostic sensitivity and the most effective prophylaxis remains to be defined.
Aims
We analysed these two unmet clinical needs in a retrospective series of 242 pts with DLBCL treated in the rituximab era.
Methods
Consecutive HIV-neg adults with DLBCL without CNS involvement treated with R-CHOP or similar were considered. CNS, mediastinal and leg-type DLBCL, high-grade transformed lymphomas and pts registered in prospective trials were excluded. Following institutional guidelines, no DLBCL pt diagnosed before 2007 received CNS prophylaxis; after 2007, CNS prophylaxis, consisting of 3-4 cycles of methotrexate 3 g/m2 ± intrathecal liposomal cytarabine (IT) was indicated in pts with high CNS recurrence risk. IT was delivered one dose per R-CHOP course, and methotrexate was delivered after R-CHOP treatment. CNS dissemination risk was defined by involvement of the testis, kidney/adrenal, spine, skull, paranasal sinuses, orbit, and/or breast or by the simultaneous presence of advanced stage and high serum LDH. In the present study, CNS dissemination risk was defined as low in pts without involvement of high-risk extranodal organs and with an International Prognostic Index (IPI) of 0-3; intermediate in pts without involvement of high-risk extranodal organs and with an IPI of 4-5; and high in pts with involvement of above-mentioned high-risk extranodal organs and with any IPI.
Results
242 pts were analysed (median age 66, range 18-89). According to the proposed model, CNS dissemination risk was low in 148 (61%) pts, intermediate in 29 (12%) and high in 65 (27%). Pts with low and intermediate risk were managed without prophylaxis, whereas this strategy was indicated in 45 high-risk pts: 35 pts received intravenous ± IT chemotherapy, 10 pts receive only IT chemotherapy due to MTHFR polymorphisms, comorbidity or old age. CNS prophylaxis was well tolerated; unexpected toxicity and interruptions due to toxicity were not recorded.At a median follow-up of 51 months (12-171), 11 (4.5%) pts experienced CNS relapse: in the brain parenchyma in 6 cases, in the meninges in the others. CNS relapse rate was <1% (1/148) in low-risk pts, 10% (3/29) in intermediate-risk, and 11% (7/65) in high-risk pts. Eight of these pts died of CNS progressive lymphoma after 7-37 months (median 12).In the high-risk subgroup, CNS relapse rate was 25% (5/20) in pts who did not receive CNS prophylaxis, 20% (2/10) in pts treated IT chemotherapy alone and 0% (0/35) in pts who received intravenous ± IT chemotherapy (p=0.004). Overall, 18 high-risk pts experienced relapse, and CNS was the most commonly involved site (7/18). Moreover, the addition of intravenous CNS prophylaxis was associated with a significantly improved PFS (3-yr: 80% vs. 42%; p=0.001) and OS (3-yr: 86% vs. 43%; p=0.00007).
Conclusion
With all the limitations of a retrospective series, this study suggest that pts with DLBCL and involvement of certain extranodal organs and/or high IPI should receive CNS prophylaxis with intravenous high-dose methotrexate and IT liposomal cytarabine. This strategy shows a relevant effect on survival of high-risk pts as CNS is a common relapse site, associated with a high mortality.
Session topic: E-poster
Keyword(s): CNS lymphoma, Diffuse large B cell lymphoma, Prophylaxis
Abstract: E963
Type: Eposter Presentation
Background
CNS dissemination is a lethal event in DLBCL. Early detection and effective CNS prophylaxis may reduce related mortality. However, risk predictors reported in the rituximab era exhibits a low diagnostic sensitivity and the most effective prophylaxis remains to be defined.
Aims
We analysed these two unmet clinical needs in a retrospective series of 242 pts with DLBCL treated in the rituximab era.
Methods
Consecutive HIV-neg adults with DLBCL without CNS involvement treated with R-CHOP or similar were considered. CNS, mediastinal and leg-type DLBCL, high-grade transformed lymphomas and pts registered in prospective trials were excluded. Following institutional guidelines, no DLBCL pt diagnosed before 2007 received CNS prophylaxis; after 2007, CNS prophylaxis, consisting of 3-4 cycles of methotrexate 3 g/m2 ± intrathecal liposomal cytarabine (IT) was indicated in pts with high CNS recurrence risk. IT was delivered one dose per R-CHOP course, and methotrexate was delivered after R-CHOP treatment. CNS dissemination risk was defined by involvement of the testis, kidney/adrenal, spine, skull, paranasal sinuses, orbit, and/or breast or by the simultaneous presence of advanced stage and high serum LDH. In the present study, CNS dissemination risk was defined as low in pts without involvement of high-risk extranodal organs and with an International Prognostic Index (IPI) of 0-3; intermediate in pts without involvement of high-risk extranodal organs and with an IPI of 4-5; and high in pts with involvement of above-mentioned high-risk extranodal organs and with any IPI.
Results
242 pts were analysed (median age 66, range 18-89). According to the proposed model, CNS dissemination risk was low in 148 (61%) pts, intermediate in 29 (12%) and high in 65 (27%). Pts with low and intermediate risk were managed without prophylaxis, whereas this strategy was indicated in 45 high-risk pts: 35 pts received intravenous ± IT chemotherapy, 10 pts receive only IT chemotherapy due to MTHFR polymorphisms, comorbidity or old age. CNS prophylaxis was well tolerated; unexpected toxicity and interruptions due to toxicity were not recorded.At a median follow-up of 51 months (12-171), 11 (4.5%) pts experienced CNS relapse: in the brain parenchyma in 6 cases, in the meninges in the others. CNS relapse rate was <1% (1/148) in low-risk pts, 10% (3/29) in intermediate-risk, and 11% (7/65) in high-risk pts. Eight of these pts died of CNS progressive lymphoma after 7-37 months (median 12).In the high-risk subgroup, CNS relapse rate was 25% (5/20) in pts who did not receive CNS prophylaxis, 20% (2/10) in pts treated IT chemotherapy alone and 0% (0/35) in pts who received intravenous ± IT chemotherapy (p=0.004). Overall, 18 high-risk pts experienced relapse, and CNS was the most commonly involved site (7/18). Moreover, the addition of intravenous CNS prophylaxis was associated with a significantly improved PFS (3-yr: 80% vs. 42%; p=0.001) and OS (3-yr: 86% vs. 43%; p=0.00007).
Conclusion
With all the limitations of a retrospective series, this study suggest that pts with DLBCL and involvement of certain extranodal organs and/or high IPI should receive CNS prophylaxis with intravenous high-dose methotrexate and IT liposomal cytarabine. This strategy shows a relevant effect on survival of high-risk pts as CNS is a common relapse site, associated with a high mortality.
Session topic: E-poster
Keyword(s): CNS lymphoma, Diffuse large B cell lymphoma, Prophylaxis
Type: Eposter Presentation
Background
CNS dissemination is a lethal event in DLBCL. Early detection and effective CNS prophylaxis may reduce related mortality. However, risk predictors reported in the rituximab era exhibits a low diagnostic sensitivity and the most effective prophylaxis remains to be defined.
Aims
We analysed these two unmet clinical needs in a retrospective series of 242 pts with DLBCL treated in the rituximab era.
Methods
Consecutive HIV-neg adults with DLBCL without CNS involvement treated with R-CHOP or similar were considered. CNS, mediastinal and leg-type DLBCL, high-grade transformed lymphomas and pts registered in prospective trials were excluded. Following institutional guidelines, no DLBCL pt diagnosed before 2007 received CNS prophylaxis; after 2007, CNS prophylaxis, consisting of 3-4 cycles of methotrexate 3 g/m2 ± intrathecal liposomal cytarabine (IT) was indicated in pts with high CNS recurrence risk. IT was delivered one dose per R-CHOP course, and methotrexate was delivered after R-CHOP treatment. CNS dissemination risk was defined by involvement of the testis, kidney/adrenal, spine, skull, paranasal sinuses, orbit, and/or breast or by the simultaneous presence of advanced stage and high serum LDH. In the present study, CNS dissemination risk was defined as low in pts without involvement of high-risk extranodal organs and with an International Prognostic Index (IPI) of 0-3; intermediate in pts without involvement of high-risk extranodal organs and with an IPI of 4-5; and high in pts with involvement of above-mentioned high-risk extranodal organs and with any IPI.
Results
242 pts were analysed (median age 66, range 18-89). According to the proposed model, CNS dissemination risk was low in 148 (61%) pts, intermediate in 29 (12%) and high in 65 (27%). Pts with low and intermediate risk were managed without prophylaxis, whereas this strategy was indicated in 45 high-risk pts: 35 pts received intravenous ± IT chemotherapy, 10 pts receive only IT chemotherapy due to MTHFR polymorphisms, comorbidity or old age. CNS prophylaxis was well tolerated; unexpected toxicity and interruptions due to toxicity were not recorded.At a median follow-up of 51 months (12-171), 11 (4.5%) pts experienced CNS relapse: in the brain parenchyma in 6 cases, in the meninges in the others. CNS relapse rate was <1% (1/148) in low-risk pts, 10% (3/29) in intermediate-risk, and 11% (7/65) in high-risk pts. Eight of these pts died of CNS progressive lymphoma after 7-37 months (median 12).In the high-risk subgroup, CNS relapse rate was 25% (5/20) in pts who did not receive CNS prophylaxis, 20% (2/10) in pts treated IT chemotherapy alone and 0% (0/35) in pts who received intravenous ± IT chemotherapy (p=0.004). Overall, 18 high-risk pts experienced relapse, and CNS was the most commonly involved site (7/18). Moreover, the addition of intravenous CNS prophylaxis was associated with a significantly improved PFS (3-yr: 80% vs. 42%; p=0.001) and OS (3-yr: 86% vs. 43%; p=0.00007).
Conclusion
With all the limitations of a retrospective series, this study suggest that pts with DLBCL and involvement of certain extranodal organs and/or high IPI should receive CNS prophylaxis with intravenous high-dose methotrexate and IT liposomal cytarabine. This strategy shows a relevant effect on survival of high-risk pts as CNS is a common relapse site, associated with a high mortality.
Session topic: E-poster
Keyword(s): CNS lymphoma, Diffuse large B cell lymphoma, Prophylaxis
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