TREATMENT TOXICITIES AND OUTCOME OF AN INTENSIVE IMMUNOCHEMOTHERAPY REGIMEN (FAB LMB96) FOR ADULT AGGRESSIVE B CELL NON-HODGKIN LYMPHOMAS (BNHL) AT RISK FOR OR WITH CENTRAL NERVOUS SYSTEM INFILTRATION
(Abstract release date: 05/19/16)
EHA Library. Desterro J. 06/09/16; 134628; PB1728
Dr. Joana Desterro
Contributions
Contributions
Abstract
Abstract: PB1728
Type: Publication Only
Background
The treatment of diffuse large B cell lymphomas (DLBCL) at risk for CNS infiltration is not well established but may benefit of regimens including systemic drugs crossing the blood-brain barrier. Furthermore, different studies have showed that patients with lymphomas with features intermediate between DLBCL and Burkitt (Int-BNHL) and MYC-rearranged lymphomas have inferior outcomes when treated with R-CHOP compared to more intensive regimens. Treatment toxicity is a major concern in this setting where a superior efficacy has yet to be prospectively established.
Aims
We retrospectively reviewed the clinical and genetic characteristics, treatment toxicities and outcomes of DLBCL patients at risk for CNS infiltration and Int-BNHL selected for aggressive treatment at our institution between 2009 and 2013.
Methods
Selection was based on age, performance status, ≥2 extranodal sites (ENS) plus elevated LDH, CNS infiltration at diagnosis or MYC-rearrangement. Fab LMB96 regimen includes alkylator/anthracycline/high-dose methotrexate-based induction and high-dose cytarabine/etoposide or cytarabine/methotrexate-based consolidation, followed by maintenance; intrathecal chemotherapy is administered at induction and consolidation. Toxicities were graded according to CTCAE. Response was defined by conventional criteria and overall survival (OS) determined from diagnosis until death or last follow up. Treatment toxicities and outcomes of stage IV, intermediate-high and high-risk IPI DLBCL patients receiving R-CHOP during the same period were reviewed for reference.
Results
15 patients with DLBCL (9) or Int-BNHL (6), median age 48 (23-65) yo, 6 men, with stage IV disease were treated with the LMB96 protocol to which Rituximab was added at the beginning of the induction and consolidation cycles. 10/11 evaluable patients had MYC rearrangements detected by FISH (MYC+). CNS involvement at presentation occurred in 3 patients and bone marrow infiltration in 6. 93% of the patients had ECOG performance status 0-1 and 12 had IPI 3-5; the other 3 patients had either CNS infiltration or MYC+.74% and 43% of 94 treatment cycles were complicated by grade 3-4 hematological and infectious toxicities, respectively. These toxicities occurred mostly during induction and consolidation. All patients were admitted for induction/consolidation cycles and required transfusion support, myeloid growth factors and IV antibiotics. Serious neurological (1%) and gastrointestinal (13%) toxicities were also observed. Dose reductions/premature interruptions occurred in 6 patients Complete response occurred in 13/14 (93%) evaluable patients. With a median follow-up of 37.8 months, 3 patients (20%) died, 2 of toxicity (13%) and 1 with progressive lymphoma; median OS was 36 months.In 40 patients with stage IV DLBCL patients aged ≤65 yo diagnosed in the same period and treated with R-CHOP (75% IPI 3-5, 90% high LDH, 65% ≥2 ENS), CR rate was 67.5%. 18/40 (45%) patients died, 14 of NHL and 2 (5%) of toxicity; median OS was 27 months.
Conclusion
In this retrospectively analyzed, single-center study we show that an intensive immunochemotherapy regimen is feasible and highly effective in selected patients with high-risk BNHL. R-CHOP, although widely applicable, demonstrated poor disease control in the reference sample. Large prospective studies are vital to assess the impact of intensive regimens in the outcome of unselected patients with aggressive lymphomas.
Session topic: E-poster
Keyword(s): Chemotherapy toxicity, Non-Hodgkin's lymphoma
Type: Publication Only
Background
The treatment of diffuse large B cell lymphomas (DLBCL) at risk for CNS infiltration is not well established but may benefit of regimens including systemic drugs crossing the blood-brain barrier. Furthermore, different studies have showed that patients with lymphomas with features intermediate between DLBCL and Burkitt (Int-BNHL) and MYC-rearranged lymphomas have inferior outcomes when treated with R-CHOP compared to more intensive regimens. Treatment toxicity is a major concern in this setting where a superior efficacy has yet to be prospectively established.
Aims
We retrospectively reviewed the clinical and genetic characteristics, treatment toxicities and outcomes of DLBCL patients at risk for CNS infiltration and Int-BNHL selected for aggressive treatment at our institution between 2009 and 2013.
Methods
Selection was based on age, performance status, ≥2 extranodal sites (ENS) plus elevated LDH, CNS infiltration at diagnosis or MYC-rearrangement. Fab LMB96 regimen includes alkylator/anthracycline/high-dose methotrexate-based induction and high-dose cytarabine/etoposide or cytarabine/methotrexate-based consolidation, followed by maintenance; intrathecal chemotherapy is administered at induction and consolidation. Toxicities were graded according to CTCAE. Response was defined by conventional criteria and overall survival (OS) determined from diagnosis until death or last follow up. Treatment toxicities and outcomes of stage IV, intermediate-high and high-risk IPI DLBCL patients receiving R-CHOP during the same period were reviewed for reference.
Results
15 patients with DLBCL (9) or Int-BNHL (6), median age 48 (23-65) yo, 6 men, with stage IV disease were treated with the LMB96 protocol to which Rituximab was added at the beginning of the induction and consolidation cycles. 10/11 evaluable patients had MYC rearrangements detected by FISH (MYC+). CNS involvement at presentation occurred in 3 patients and bone marrow infiltration in 6. 93% of the patients had ECOG performance status 0-1 and 12 had IPI 3-5; the other 3 patients had either CNS infiltration or MYC+.74% and 43% of 94 treatment cycles were complicated by grade 3-4 hematological and infectious toxicities, respectively. These toxicities occurred mostly during induction and consolidation. All patients were admitted for induction/consolidation cycles and required transfusion support, myeloid growth factors and IV antibiotics. Serious neurological (1%) and gastrointestinal (13%) toxicities were also observed. Dose reductions/premature interruptions occurred in 6 patients Complete response occurred in 13/14 (93%) evaluable patients. With a median follow-up of 37.8 months, 3 patients (20%) died, 2 of toxicity (13%) and 1 with progressive lymphoma; median OS was 36 months.In 40 patients with stage IV DLBCL patients aged ≤65 yo diagnosed in the same period and treated with R-CHOP (75% IPI 3-5, 90% high LDH, 65% ≥2 ENS), CR rate was 67.5%. 18/40 (45%) patients died, 14 of NHL and 2 (5%) of toxicity; median OS was 27 months.
Conclusion
In this retrospectively analyzed, single-center study we show that an intensive immunochemotherapy regimen is feasible and highly effective in selected patients with high-risk BNHL. R-CHOP, although widely applicable, demonstrated poor disease control in the reference sample. Large prospective studies are vital to assess the impact of intensive regimens in the outcome of unselected patients with aggressive lymphomas.
Session topic: E-poster
Keyword(s): Chemotherapy toxicity, Non-Hodgkin's lymphoma
Abstract: PB1728
Type: Publication Only
Background
The treatment of diffuse large B cell lymphomas (DLBCL) at risk for CNS infiltration is not well established but may benefit of regimens including systemic drugs crossing the blood-brain barrier. Furthermore, different studies have showed that patients with lymphomas with features intermediate between DLBCL and Burkitt (Int-BNHL) and MYC-rearranged lymphomas have inferior outcomes when treated with R-CHOP compared to more intensive regimens. Treatment toxicity is a major concern in this setting where a superior efficacy has yet to be prospectively established.
Aims
We retrospectively reviewed the clinical and genetic characteristics, treatment toxicities and outcomes of DLBCL patients at risk for CNS infiltration and Int-BNHL selected for aggressive treatment at our institution between 2009 and 2013.
Methods
Selection was based on age, performance status, ≥2 extranodal sites (ENS) plus elevated LDH, CNS infiltration at diagnosis or MYC-rearrangement. Fab LMB96 regimen includes alkylator/anthracycline/high-dose methotrexate-based induction and high-dose cytarabine/etoposide or cytarabine/methotrexate-based consolidation, followed by maintenance; intrathecal chemotherapy is administered at induction and consolidation. Toxicities were graded according to CTCAE. Response was defined by conventional criteria and overall survival (OS) determined from diagnosis until death or last follow up. Treatment toxicities and outcomes of stage IV, intermediate-high and high-risk IPI DLBCL patients receiving R-CHOP during the same period were reviewed for reference.
Results
15 patients with DLBCL (9) or Int-BNHL (6), median age 48 (23-65) yo, 6 men, with stage IV disease were treated with the LMB96 protocol to which Rituximab was added at the beginning of the induction and consolidation cycles. 10/11 evaluable patients had MYC rearrangements detected by FISH (MYC+). CNS involvement at presentation occurred in 3 patients and bone marrow infiltration in 6. 93% of the patients had ECOG performance status 0-1 and 12 had IPI 3-5; the other 3 patients had either CNS infiltration or MYC+.74% and 43% of 94 treatment cycles were complicated by grade 3-4 hematological and infectious toxicities, respectively. These toxicities occurred mostly during induction and consolidation. All patients were admitted for induction/consolidation cycles and required transfusion support, myeloid growth factors and IV antibiotics. Serious neurological (1%) and gastrointestinal (13%) toxicities were also observed. Dose reductions/premature interruptions occurred in 6 patients Complete response occurred in 13/14 (93%) evaluable patients. With a median follow-up of 37.8 months, 3 patients (20%) died, 2 of toxicity (13%) and 1 with progressive lymphoma; median OS was 36 months.In 40 patients with stage IV DLBCL patients aged ≤65 yo diagnosed in the same period and treated with R-CHOP (75% IPI 3-5, 90% high LDH, 65% ≥2 ENS), CR rate was 67.5%. 18/40 (45%) patients died, 14 of NHL and 2 (5%) of toxicity; median OS was 27 months.
Conclusion
In this retrospectively analyzed, single-center study we show that an intensive immunochemotherapy regimen is feasible and highly effective in selected patients with high-risk BNHL. R-CHOP, although widely applicable, demonstrated poor disease control in the reference sample. Large prospective studies are vital to assess the impact of intensive regimens in the outcome of unselected patients with aggressive lymphomas.
Session topic: E-poster
Keyword(s): Chemotherapy toxicity, Non-Hodgkin's lymphoma
Type: Publication Only
Background
The treatment of diffuse large B cell lymphomas (DLBCL) at risk for CNS infiltration is not well established but may benefit of regimens including systemic drugs crossing the blood-brain barrier. Furthermore, different studies have showed that patients with lymphomas with features intermediate between DLBCL and Burkitt (Int-BNHL) and MYC-rearranged lymphomas have inferior outcomes when treated with R-CHOP compared to more intensive regimens. Treatment toxicity is a major concern in this setting where a superior efficacy has yet to be prospectively established.
Aims
We retrospectively reviewed the clinical and genetic characteristics, treatment toxicities and outcomes of DLBCL patients at risk for CNS infiltration and Int-BNHL selected for aggressive treatment at our institution between 2009 and 2013.
Methods
Selection was based on age, performance status, ≥2 extranodal sites (ENS) plus elevated LDH, CNS infiltration at diagnosis or MYC-rearrangement. Fab LMB96 regimen includes alkylator/anthracycline/high-dose methotrexate-based induction and high-dose cytarabine/etoposide or cytarabine/methotrexate-based consolidation, followed by maintenance; intrathecal chemotherapy is administered at induction and consolidation. Toxicities were graded according to CTCAE. Response was defined by conventional criteria and overall survival (OS) determined from diagnosis until death or last follow up. Treatment toxicities and outcomes of stage IV, intermediate-high and high-risk IPI DLBCL patients receiving R-CHOP during the same period were reviewed for reference.
Results
15 patients with DLBCL (9) or Int-BNHL (6), median age 48 (23-65) yo, 6 men, with stage IV disease were treated with the LMB96 protocol to which Rituximab was added at the beginning of the induction and consolidation cycles. 10/11 evaluable patients had MYC rearrangements detected by FISH (MYC+). CNS involvement at presentation occurred in 3 patients and bone marrow infiltration in 6. 93% of the patients had ECOG performance status 0-1 and 12 had IPI 3-5; the other 3 patients had either CNS infiltration or MYC+.74% and 43% of 94 treatment cycles were complicated by grade 3-4 hematological and infectious toxicities, respectively. These toxicities occurred mostly during induction and consolidation. All patients were admitted for induction/consolidation cycles and required transfusion support, myeloid growth factors and IV antibiotics. Serious neurological (1%) and gastrointestinal (13%) toxicities were also observed. Dose reductions/premature interruptions occurred in 6 patients Complete response occurred in 13/14 (93%) evaluable patients. With a median follow-up of 37.8 months, 3 patients (20%) died, 2 of toxicity (13%) and 1 with progressive lymphoma; median OS was 36 months.In 40 patients with stage IV DLBCL patients aged ≤65 yo diagnosed in the same period and treated with R-CHOP (75% IPI 3-5, 90% high LDH, 65% ≥2 ENS), CR rate was 67.5%. 18/40 (45%) patients died, 14 of NHL and 2 (5%) of toxicity; median OS was 27 months.
Conclusion
In this retrospectively analyzed, single-center study we show that an intensive immunochemotherapy regimen is feasible and highly effective in selected patients with high-risk BNHL. R-CHOP, although widely applicable, demonstrated poor disease control in the reference sample. Large prospective studies are vital to assess the impact of intensive regimens in the outcome of unselected patients with aggressive lymphomas.
Session topic: E-poster
Keyword(s): Chemotherapy toxicity, Non-Hodgkin's lymphoma
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