RETROSPECTIVE EVALUATION ON EFFICACY AND FEASIBILITY OF R-CODOX-M/IVAC REGIMEN IN AGGRESSIVE DLBCL
(Abstract release date: 05/18/17)
EHA Library. Coviello E. 05/18/17; 182446; PB1732
Dr. Elisa Coviello
Contributions
Contributions
Abstract
Abstract: PB1732
Type: Publication Only
Background
Diffuse Large B Cell Lymphoma (DLBCL) is an heterogeneous group of diseases. The aggressive behavior can be predicted by clinical risk scores, immunohistochemistry and cytogenetic. Among DLBCL, double hit lymphomas (DHL) and double or triple-protein-expression lymphomas (DPLs, TPLs) display a worse outcome. R-CHOP, which is the frontline treatment for DLBCL, showed a poor outcome in high risk IPI patients and DHLs or DPLs. From January 2011 in our centre (IRCCS AOU San Martino Hospital–IST, Genoa, Italy) R-CODOX-M/IVAC regimen has been adopted as first line in patients with aggressive DLBCL, defined by at least one among these features: high tumour burden, DPLs, IPI score >3 or by the presence of at least 1 extranodal site.
Aims
Our aim was to define the efficacy and feasibility of this frontline strategy and eventually identify the subgroups of patients who may benefit from this approach.
Methods
We retrospectively analyzed 20 patients affected by aggressive DLBCL treated with R-CODOX-M/IVAC. R-CODOX-M consists of rituximab 375 mg/sqm day 1, cyclophosphamide 800 mg/sqm day 1, 200 mg day 2-5, doxorubicin 40 mg/sqm day 1, vincristine 1,4 mg/sqm, methotrexate 6700 mg/sqm. IVAC-R contains rituximab 375 mg/sqm, iphosphamide 1500 mg/sqm day 1-5, etoposide 60 mg/sqm day 1-5, cytarabine 2000 mg/sqm bid day 1-2. In both cycles CNS prophylaxis was administered. According to Ann Arbor classification, 11 patients were on stage IV, 1 on stage III, 3 in stage II and 5 in stage I. Twelve patients had B symptoms. Median IPI score was 3. Eleven patients had DPLs and 4 of them had TPLs. Overall survival (OS) was calculated from the time of diagnosis to the dime of death or last follow-up.
Results
After a median follow-up of 28 months, 5 patients died (25%), OS at six and twelve months was 89,4 and 70,4%, respectively, median not reached (NR). Complete remission was achieved in 11 patients (69%), partial remission in 2 patients (13%). The overall response rate was 82%. Three patients (18%) were primary refractory. Among DPLs, OS at six and twelve months was 88,9 and 64,8%, respectively, not significantly lower than non DPLs patients (p=n.s., median NR).
In patients with Ann Arbour stage III or IV, OS at six and twelve months was 90,9 and 60,6% (median NR). In patients with IPI score >3, OS at six and twelve months was 78,8 and 45% (median 12 months).
The main toxicity during CODOX-M was grade >2 mucositis, 63% of patients. Infections occurred in 71% of patients. Renal and liver toxicity was mainly of low grade and was observed respectively in 38% and 50% of patients. Median severe neutropenia was 4,5 days (range 0-16) and median severe thrombocytopenia was only 1 day (range 0-21). Most patients (56%) needed transfusion support. In IVAC regimen the main toxicity was the haematological one with 7 days of median duration of severe neutropenia (range 3-10), and 7 days (range 6-23) of thrombocytopenia. Seventy-five patients required transfusion support. Infections occurred in 42% of patients. We observed few case of grade >2 mucositis (17%), renal toxicity (8%) and liver toxicity (17%).
Conclusion
R-CODOX-M/IVAC is a generally well tolerated regimen, with acceptable toxicity profile in the setting of aggressive DLBCL. Results in our cohort suggest a potential benefit for DPLs, whereas higher IPI scores retains a negative prognostic impact. The next step of the study will be retrospective FISH evaluation of C-MYC, BCL2 and BCL6 translocations, for lacking patients in our cohort, in order to disclose a potential benefit for double or triple hit lymphomas.
Session topic: 20. Aggressive Non-Hodgkin lymphoma - Clinical
Keyword(s): DLBCL, BCL6, BCL2, MYC
Abstract: PB1732
Type: Publication Only
Background
Diffuse Large B Cell Lymphoma (DLBCL) is an heterogeneous group of diseases. The aggressive behavior can be predicted by clinical risk scores, immunohistochemistry and cytogenetic. Among DLBCL, double hit lymphomas (DHL) and double or triple-protein-expression lymphomas (DPLs, TPLs) display a worse outcome. R-CHOP, which is the frontline treatment for DLBCL, showed a poor outcome in high risk IPI patients and DHLs or DPLs. From January 2011 in our centre (IRCCS AOU San Martino Hospital–IST, Genoa, Italy) R-CODOX-M/IVAC regimen has been adopted as first line in patients with aggressive DLBCL, defined by at least one among these features: high tumour burden, DPLs, IPI score >3 or by the presence of at least 1 extranodal site.
Aims
Our aim was to define the efficacy and feasibility of this frontline strategy and eventually identify the subgroups of patients who may benefit from this approach.
Methods
We retrospectively analyzed 20 patients affected by aggressive DLBCL treated with R-CODOX-M/IVAC. R-CODOX-M consists of rituximab 375 mg/sqm day 1, cyclophosphamide 800 mg/sqm day 1, 200 mg day 2-5, doxorubicin 40 mg/sqm day 1, vincristine 1,4 mg/sqm, methotrexate 6700 mg/sqm. IVAC-R contains rituximab 375 mg/sqm, iphosphamide 1500 mg/sqm day 1-5, etoposide 60 mg/sqm day 1-5, cytarabine 2000 mg/sqm bid day 1-2. In both cycles CNS prophylaxis was administered. According to Ann Arbor classification, 11 patients were on stage IV, 1 on stage III, 3 in stage II and 5 in stage I. Twelve patients had B symptoms. Median IPI score was 3. Eleven patients had DPLs and 4 of them had TPLs. Overall survival (OS) was calculated from the time of diagnosis to the dime of death or last follow-up.
Results
After a median follow-up of 28 months, 5 patients died (25%), OS at six and twelve months was 89,4 and 70,4%, respectively, median not reached (NR). Complete remission was achieved in 11 patients (69%), partial remission in 2 patients (13%). The overall response rate was 82%. Three patients (18%) were primary refractory. Among DPLs, OS at six and twelve months was 88,9 and 64,8%, respectively, not significantly lower than non DPLs patients (p=n.s., median NR).
In patients with Ann Arbour stage III or IV, OS at six and twelve months was 90,9 and 60,6% (median NR). In patients with IPI score >3, OS at six and twelve months was 78,8 and 45% (median 12 months).
The main toxicity during CODOX-M was grade >2 mucositis, 63% of patients. Infections occurred in 71% of patients. Renal and liver toxicity was mainly of low grade and was observed respectively in 38% and 50% of patients. Median severe neutropenia was 4,5 days (range 0-16) and median severe thrombocytopenia was only 1 day (range 0-21). Most patients (56%) needed transfusion support. In IVAC regimen the main toxicity was the haematological one with 7 days of median duration of severe neutropenia (range 3-10), and 7 days (range 6-23) of thrombocytopenia. Seventy-five patients required transfusion support. Infections occurred in 42% of patients. We observed few case of grade >2 mucositis (17%), renal toxicity (8%) and liver toxicity (17%).
Conclusion
R-CODOX-M/IVAC is a generally well tolerated regimen, with acceptable toxicity profile in the setting of aggressive DLBCL. Results in our cohort suggest a potential benefit for DPLs, whereas higher IPI scores retains a negative prognostic impact. The next step of the study will be retrospective FISH evaluation of C-MYC, BCL2 and BCL6 translocations, for lacking patients in our cohort, in order to disclose a potential benefit for double or triple hit lymphomas.
Session topic: 20. Aggressive Non-Hodgkin lymphoma - Clinical
Keyword(s): DLBCL, BCL6, BCL2, MYC
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