SIDE EFFECTS AFTER RITUXIMAB INFUSION IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA
(Abstract release date: 05/21/15)
EHA Library. D'Arena G. 06/12/15; 102612; PB1724
Disclosure(s): IRCCS Centro di Riferimento Oncologico della BasilicataHematology and Stem Cell Transplantation Unit
Dr. Giovanni D'Arena
Contributions
Contributions
Abstract
Abstract: PB1724
Type: Publication Only
Background
The anti-CD20 monoclonal antibody rituximab is approved for the treatment of non-Hodgkin’s lymphomas (NHL) and chronic lymphocytic leukemia (CLL). Infusional side effects are commonly seen during rituximab administration, mostly in the first cycle and in patients with high tumor load. Severe adverse events (SAE) may also occur, following which the drug needs to be definitively stopped in some cases. Very recently, Norin et al, have reported data of a Swedish national observational study focusing on SAE occurring in patients with CLL who underwent rituximab treatment (Leuk Res, 2015). These Authors evaluated 96 patients and found that 58% of them experienced at least one adverse drug reaction (ADR) during the first cycle. Only 5 patients (5%), however, reported grade > 3 ADRs, with one grade 4 reactions. Only 2 patients had a leukocyte count > 50.000/mL and no correlation between leukocyte count and ADR grade was found.
Aims
Starting in October, 2014, we are conducting a retrospective Italian multicenter study aiming to evaluate the incidence of side effects in patients treated in the last 5 years at our Institutions with rituximab for their hematologic malignancies or autoimmune disorders. We choose to focus on ADRs occurred in CLL patients aiming to evaluate the incidence of infusional side effects and, possibly, its correlation with clinico-biological features evaluated immediately before to start therapy.
Methods
To date, 130 patients have been evaluated: 60 with CLL, 34 with non-Hodgkin’s diffuse large B-cell lymphomas, 33 with non-Hodgkin’s indolent lymphomas, 1 with Hodgkin’s lymphomas with lymphocyte predominance, and 2 with autoimmune disorders (1 immune thrombocytopenia and 1 acquired hemophilia A). Sixty patients with immunologically typical CLL were evaluated (40 were male and 20 female; mean age was 66,4 years, range 46-86; 1 patient with Rai stage 1; 29 patients stage 2; 17 stage 3; and 13 stage 4). Rituximab was given as first line treatment and variously combined with different drugs, the most used being fludarabine, cyclophosphamide, chlorambucil and bendamustine.
Results
Twenty-three patients (38%) experienced an adverse event during the first infusion of rituximab, while 37 patients (62%) did not. Overall, 13 patients (57%) had grade 1, 7 (30%) grade 2, 1 (4%) grade 3, and 2 (9%) grade 4 ADRs, according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE). No correlation was found with age, gender, concomitant presence of an autoimmune hemolytic anemia, spleen and lymph node involvement, platelet count, and type of associated-chemotherapy. Degree of bone marrow infiltration (p 0.03) and the concomitant infusion of rituximab plus chemotherapy with respect to a delayed administration (p 0.007) were significantly associated with the occurrence of ADRs. Quite surprisingly, patients with more elevated hemoglobin levels (p 0.02) and those with lower peripheral lymphocyte counts (p 0.03) displayed a greater risk to develop ADRs; these last patients also showed more severe ADRs. Most of side effects were easily managed. In the majority of cases rituximab was temporarily stopped, while steroids and anti-histaminic drugs were given. The monoclonal antibody was then safely re-started with a less rapid infusion. Only one patient definitively stopped rituximab treatment, due to grade 4 ADR (shock and dyspnea).
Summary
Overall, in our multicenter experience, side effects after rituximab were commonly seen in CLL patients during the first infusion. However, they were mostly limited to grade 1 and 2 (mild-moderate) and were easily managed. Rituximab was generally re-administered during the same course of the treatment. Only very few patients experienced severe infusion-related ADRs and rarely the monoclonal antibody had to be definitively stopped. Clinico-biological variables, including pharmacogenomic parameters, that could be useful in predicting the development of infusional side-effects are warranted in order to identify patients at higher risk for ADR and to develop appropriate preventing therapies.
Keyword(s): Chronic lymphocytic leukemia, Rituximab, Side effects
Session topic: Publication Only
Type: Publication Only
Background
The anti-CD20 monoclonal antibody rituximab is approved for the treatment of non-Hodgkin’s lymphomas (NHL) and chronic lymphocytic leukemia (CLL). Infusional side effects are commonly seen during rituximab administration, mostly in the first cycle and in patients with high tumor load. Severe adverse events (SAE) may also occur, following which the drug needs to be definitively stopped in some cases. Very recently, Norin et al, have reported data of a Swedish national observational study focusing on SAE occurring in patients with CLL who underwent rituximab treatment (Leuk Res, 2015). These Authors evaluated 96 patients and found that 58% of them experienced at least one adverse drug reaction (ADR) during the first cycle. Only 5 patients (5%), however, reported grade > 3 ADRs, with one grade 4 reactions. Only 2 patients had a leukocyte count > 50.000/mL and no correlation between leukocyte count and ADR grade was found.
Aims
Starting in October, 2014, we are conducting a retrospective Italian multicenter study aiming to evaluate the incidence of side effects in patients treated in the last 5 years at our Institutions with rituximab for their hematologic malignancies or autoimmune disorders. We choose to focus on ADRs occurred in CLL patients aiming to evaluate the incidence of infusional side effects and, possibly, its correlation with clinico-biological features evaluated immediately before to start therapy.
Methods
To date, 130 patients have been evaluated: 60 with CLL, 34 with non-Hodgkin’s diffuse large B-cell lymphomas, 33 with non-Hodgkin’s indolent lymphomas, 1 with Hodgkin’s lymphomas with lymphocyte predominance, and 2 with autoimmune disorders (1 immune thrombocytopenia and 1 acquired hemophilia A). Sixty patients with immunologically typical CLL were evaluated (40 were male and 20 female; mean age was 66,4 years, range 46-86; 1 patient with Rai stage 1; 29 patients stage 2; 17 stage 3; and 13 stage 4). Rituximab was given as first line treatment and variously combined with different drugs, the most used being fludarabine, cyclophosphamide, chlorambucil and bendamustine.
Results
Twenty-three patients (38%) experienced an adverse event during the first infusion of rituximab, while 37 patients (62%) did not. Overall, 13 patients (57%) had grade 1, 7 (30%) grade 2, 1 (4%) grade 3, and 2 (9%) grade 4 ADRs, according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE). No correlation was found with age, gender, concomitant presence of an autoimmune hemolytic anemia, spleen and lymph node involvement, platelet count, and type of associated-chemotherapy. Degree of bone marrow infiltration (p 0.03) and the concomitant infusion of rituximab plus chemotherapy with respect to a delayed administration (p 0.007) were significantly associated with the occurrence of ADRs. Quite surprisingly, patients with more elevated hemoglobin levels (p 0.02) and those with lower peripheral lymphocyte counts (p 0.03) displayed a greater risk to develop ADRs; these last patients also showed more severe ADRs. Most of side effects were easily managed. In the majority of cases rituximab was temporarily stopped, while steroids and anti-histaminic drugs were given. The monoclonal antibody was then safely re-started with a less rapid infusion. Only one patient definitively stopped rituximab treatment, due to grade 4 ADR (shock and dyspnea).
Summary
Overall, in our multicenter experience, side effects after rituximab were commonly seen in CLL patients during the first infusion. However, they were mostly limited to grade 1 and 2 (mild-moderate) and were easily managed. Rituximab was generally re-administered during the same course of the treatment. Only very few patients experienced severe infusion-related ADRs and rarely the monoclonal antibody had to be definitively stopped. Clinico-biological variables, including pharmacogenomic parameters, that could be useful in predicting the development of infusional side-effects are warranted in order to identify patients at higher risk for ADR and to develop appropriate preventing therapies.
Keyword(s): Chronic lymphocytic leukemia, Rituximab, Side effects
Session topic: Publication Only
Abstract: PB1724
Type: Publication Only
Background
The anti-CD20 monoclonal antibody rituximab is approved for the treatment of non-Hodgkin’s lymphomas (NHL) and chronic lymphocytic leukemia (CLL). Infusional side effects are commonly seen during rituximab administration, mostly in the first cycle and in patients with high tumor load. Severe adverse events (SAE) may also occur, following which the drug needs to be definitively stopped in some cases. Very recently, Norin et al, have reported data of a Swedish national observational study focusing on SAE occurring in patients with CLL who underwent rituximab treatment (Leuk Res, 2015). These Authors evaluated 96 patients and found that 58% of them experienced at least one adverse drug reaction (ADR) during the first cycle. Only 5 patients (5%), however, reported grade > 3 ADRs, with one grade 4 reactions. Only 2 patients had a leukocyte count > 50.000/mL and no correlation between leukocyte count and ADR grade was found.
Aims
Starting in October, 2014, we are conducting a retrospective Italian multicenter study aiming to evaluate the incidence of side effects in patients treated in the last 5 years at our Institutions with rituximab for their hematologic malignancies or autoimmune disorders. We choose to focus on ADRs occurred in CLL patients aiming to evaluate the incidence of infusional side effects and, possibly, its correlation with clinico-biological features evaluated immediately before to start therapy.
Methods
To date, 130 patients have been evaluated: 60 with CLL, 34 with non-Hodgkin’s diffuse large B-cell lymphomas, 33 with non-Hodgkin’s indolent lymphomas, 1 with Hodgkin’s lymphomas with lymphocyte predominance, and 2 with autoimmune disorders (1 immune thrombocytopenia and 1 acquired hemophilia A). Sixty patients with immunologically typical CLL were evaluated (40 were male and 20 female; mean age was 66,4 years, range 46-86; 1 patient with Rai stage 1; 29 patients stage 2; 17 stage 3; and 13 stage 4). Rituximab was given as first line treatment and variously combined with different drugs, the most used being fludarabine, cyclophosphamide, chlorambucil and bendamustine.
Results
Twenty-three patients (38%) experienced an adverse event during the first infusion of rituximab, while 37 patients (62%) did not. Overall, 13 patients (57%) had grade 1, 7 (30%) grade 2, 1 (4%) grade 3, and 2 (9%) grade 4 ADRs, according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE). No correlation was found with age, gender, concomitant presence of an autoimmune hemolytic anemia, spleen and lymph node involvement, platelet count, and type of associated-chemotherapy. Degree of bone marrow infiltration (p 0.03) and the concomitant infusion of rituximab plus chemotherapy with respect to a delayed administration (p 0.007) were significantly associated with the occurrence of ADRs. Quite surprisingly, patients with more elevated hemoglobin levels (p 0.02) and those with lower peripheral lymphocyte counts (p 0.03) displayed a greater risk to develop ADRs; these last patients also showed more severe ADRs. Most of side effects were easily managed. In the majority of cases rituximab was temporarily stopped, while steroids and anti-histaminic drugs were given. The monoclonal antibody was then safely re-started with a less rapid infusion. Only one patient definitively stopped rituximab treatment, due to grade 4 ADR (shock and dyspnea).
Summary
Overall, in our multicenter experience, side effects after rituximab were commonly seen in CLL patients during the first infusion. However, they were mostly limited to grade 1 and 2 (mild-moderate) and were easily managed. Rituximab was generally re-administered during the same course of the treatment. Only very few patients experienced severe infusion-related ADRs and rarely the monoclonal antibody had to be definitively stopped. Clinico-biological variables, including pharmacogenomic parameters, that could be useful in predicting the development of infusional side-effects are warranted in order to identify patients at higher risk for ADR and to develop appropriate preventing therapies.
Keyword(s): Chronic lymphocytic leukemia, Rituximab, Side effects
Session topic: Publication Only
Type: Publication Only
Background
The anti-CD20 monoclonal antibody rituximab is approved for the treatment of non-Hodgkin’s lymphomas (NHL) and chronic lymphocytic leukemia (CLL). Infusional side effects are commonly seen during rituximab administration, mostly in the first cycle and in patients with high tumor load. Severe adverse events (SAE) may also occur, following which the drug needs to be definitively stopped in some cases. Very recently, Norin et al, have reported data of a Swedish national observational study focusing on SAE occurring in patients with CLL who underwent rituximab treatment (Leuk Res, 2015). These Authors evaluated 96 patients and found that 58% of them experienced at least one adverse drug reaction (ADR) during the first cycle. Only 5 patients (5%), however, reported grade > 3 ADRs, with one grade 4 reactions. Only 2 patients had a leukocyte count > 50.000/mL and no correlation between leukocyte count and ADR grade was found.
Aims
Starting in October, 2014, we are conducting a retrospective Italian multicenter study aiming to evaluate the incidence of side effects in patients treated in the last 5 years at our Institutions with rituximab for their hematologic malignancies or autoimmune disorders. We choose to focus on ADRs occurred in CLL patients aiming to evaluate the incidence of infusional side effects and, possibly, its correlation with clinico-biological features evaluated immediately before to start therapy.
Methods
To date, 130 patients have been evaluated: 60 with CLL, 34 with non-Hodgkin’s diffuse large B-cell lymphomas, 33 with non-Hodgkin’s indolent lymphomas, 1 with Hodgkin’s lymphomas with lymphocyte predominance, and 2 with autoimmune disorders (1 immune thrombocytopenia and 1 acquired hemophilia A). Sixty patients with immunologically typical CLL were evaluated (40 were male and 20 female; mean age was 66,4 years, range 46-86; 1 patient with Rai stage 1; 29 patients stage 2; 17 stage 3; and 13 stage 4). Rituximab was given as first line treatment and variously combined with different drugs, the most used being fludarabine, cyclophosphamide, chlorambucil and bendamustine.
Results
Twenty-three patients (38%) experienced an adverse event during the first infusion of rituximab, while 37 patients (62%) did not. Overall, 13 patients (57%) had grade 1, 7 (30%) grade 2, 1 (4%) grade 3, and 2 (9%) grade 4 ADRs, according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE). No correlation was found with age, gender, concomitant presence of an autoimmune hemolytic anemia, spleen and lymph node involvement, platelet count, and type of associated-chemotherapy. Degree of bone marrow infiltration (p 0.03) and the concomitant infusion of rituximab plus chemotherapy with respect to a delayed administration (p 0.007) were significantly associated with the occurrence of ADRs. Quite surprisingly, patients with more elevated hemoglobin levels (p 0.02) and those with lower peripheral lymphocyte counts (p 0.03) displayed a greater risk to develop ADRs; these last patients also showed more severe ADRs. Most of side effects were easily managed. In the majority of cases rituximab was temporarily stopped, while steroids and anti-histaminic drugs were given. The monoclonal antibody was then safely re-started with a less rapid infusion. Only one patient definitively stopped rituximab treatment, due to grade 4 ADR (shock and dyspnea).
Summary
Overall, in our multicenter experience, side effects after rituximab were commonly seen in CLL patients during the first infusion. However, they were mostly limited to grade 1 and 2 (mild-moderate) and were easily managed. Rituximab was generally re-administered during the same course of the treatment. Only very few patients experienced severe infusion-related ADRs and rarely the monoclonal antibody had to be definitively stopped. Clinico-biological variables, including pharmacogenomic parameters, that could be useful in predicting the development of infusional side-effects are warranted in order to identify patients at higher risk for ADR and to develop appropriate preventing therapies.
Keyword(s): Chronic lymphocytic leukemia, Rituximab, Side effects
Session topic: Publication Only
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