Description
In the online pharmacy “Onko Apteka KZ” you can buy Acellbia Rituximab inexpensively with fast delivery! All drugs have quality certificates! We comply with transportation requirements during delivery! Various payment and delivery methods! Delivery from 1 hour! All parcels are insured. Find out all the conditions by phone: for Kazakhstan and Russia (Moscow number) 8 (926) 924-95-33 (Viber and WhatsApp available).
- Acellbia Rituximab 100 mg: 55399 KZT.
- Acellbia Rituximab 500 mg: 109427 KZT.
Acellbia is presented in the form of a practically colorless liquid. The active ingredient is rituximab. The composition also includes hydrochloric acid, polysorbate, sodium citrate.
Acellbia, 10 mg/ml, concentrate for solution for infusion, 10 ml, 2 pcs.
To assess the frequency of adverse reactions, the following criteria are used: very often (≥10%); often (≥1% - <10%); uncommon (≥0.1% - <1%).
Rituximab in the treatment of low-grade or follicular non-Hodgkin lymphoma - monotherapy/maintenance therapy.
Adverse reactions were reported up to 12 months after monotherapy and up to 1 month after rituximab maintenance therapy.
Infectious and parasitic diseases:
very often - bacterial and viral infections; often - respiratory tract infections*, pneumonia*, sepsis, herpes zoster*, infections accompanied by fever*, fungal infections, infections of unknown etiology.
From the blood and lymphatic system:
very often - leukopenia, neutropenia; often - thrombocytopenia, anemia; uncommon - lymphadenopathy, bleeding disorder, transient partial aplastic anemia, hemolytic anemia.
From the respiratory system, chest and mediastinal organs:
often - rhinitis, bronchospasm, cough, respiratory diseases, shortness of breath, chest pain; uncommon - hypoxia, impaired pulmonary function, bronchiolitis obliterans, bronchial asthma.
From the immune system:
very often - angioedema; often - hypersensitivity reactions.
Metabolism and nutrition:
often - hyperglycemia, weight loss, peripheral edema, facial edema, increased LDH activity, hypocalcemia.
General disorders and disorders at the injection site:
very often - headache, fever, chills, asthenia; often - pain in tumor foci, flu-like syndrome, hot flashes, weakness; Uncommon: pain at the injection site.
From the gastrointestinal tract:
very often - nausea; often - vomiting, diarrhea, dyspepsia, lack of appetite, dysphagia, stomatitis, constipation, abdominal pain, sore throat; infrequently - abdominal enlargement.
From the SSS side:
often - decreased blood pressure, increased blood pressure, orthostatic hypotension, tachycardia, arrhythmia, atrial fibrillation*, cardiac pathology*; uncommon - left ventricular heart failure*, ventricular and supraventricular tachycardia*, bradycardia, myocardial ischemia*, angina*.
From the nervous system:
often - dizziness, paresthesia, hypoesthesia, sleep disturbance, anxiety, agitation, vasodilation; infrequently - perversion of taste.
Mental disorders:
infrequently - nervousness, depression.
From the musculoskeletal system:
often - myalgia, arthralgia, muscle hypertonicity, back pain, neck pain, pain.
For the skin and subcutaneous tissues:
very often - itching, rash; often - urticaria, increased sweating at night, sweating, alopecia*.
From the side of the organ of vision:
often - lacrimation disorders, conjunctivitis.
Hearing and labyrinth disorders:
often - pain and noise in the ears.
Laboratory and instrumental data:
very often - a decrease in
IgG
.
*Frequencies are only for adverse reactions grade ≥3 according to National Cancer Institute Toxicity Criteria ( NCI-CTC)
).
Rituximab in combination with chemotherapy ( R-CHOP
,
R-CVP
,
R-FC
) for non-Hodgkin's lymphoma and chronic lymphocytic leukemia
The following are severe adverse reactions in addition to those observed with monotherapy/maintenance therapy and/or occurring at a higher frequency.
Infectious and parasitic diseases:
very often - bronchitis; often - acute bronchitis, sinusitis, hepatitis B* (exacerbation and primary infection).
From the blood and lymphatic system:
very often - neutropenia**, febrile neutropenia, thrombocytopenia; often - pancytopenia, granulocytopenia.
For the skin and subcutaneous tissues:
very often - alopecia; often - skin diseases.
General disorders and disorders at the injection site:
often - fatigue, chills.
* Frequency is indicated based on observations during the treatment of relapsed/chemoresistant chronic lymphocytic leukemia according to the R-FC
.
R-FC therapy
previously untreated patients or in patients with relapsed/chemoresistant chronic lymphocytic leukemia.
The following are adverse events that occurred during rituximab therapy with equal frequency (or less frequently) compared to the control group: hematotoxicity, neutropenic infections, urinary tract infections, septic shock, pulmonary superinfections, implant infections, staphylococcal septicemia, mucous nasal discharge, pulmonary edema , heart failure, sensitivity disorders, venous thrombosis, incl. deep vein thrombosis of the extremities, mucositis, edema of the lower extremities, decreased left ventricular ejection fraction, increased temperature, deterioration of general health, bacteremia, multiple organ failure, decompensation of diabetes mellitus.
Safety profile of rituximab in combination with chemotherapy according to MCP
CHVP-IFN
does not differ from that when the drug is combined with
CVP
,
CHOP
or
FC
in matched populations
Infusion reactions
Rituximab monotherapy (for 4 weeks)
More than 50% of patients experienced events resembling infusion reactions, most often during the first infusions. Infusion reactions include chills, trembling, weakness, shortness of breath, nausea, rash, hot flashes, decreased blood pressure, fever, itching, urticaria, irritation of the tongue or swelling of the larynx (angioedema), rhinitis, vomiting, pain in tumor areas, headache, bronchospasm . The development of signs of tumor lysis syndrome has been reported.
Rituximab in combination with chemotherapy according to the following regimens: R-CVP
- for non-Hodgkin's lymphoma;
R-CHOP
- for diffuse large B-cell non-Hodgkin lymphoma;
R-FC
- for chronic lymphocytic leukemia
Grade 3 and 4 infusion reactions during infusion or within 24 hours after rituximab infusion were observed during the first cycle of chemotherapy in 12% of patients. The incidence of infusion reactions decreased with each subsequent cycle and by the 8th cycle of chemotherapy, the incidence of infusion reactions decreased to less than 1%. Infusion reactions, in addition to those mentioned above (with rituximab monotherapy), included: dyspepsia, rash, increased blood pressure, tachycardia, signs of tumor lysis syndrome, in some cases - myocardial infarction, atrial fibrillation, pulmonary edema and acute reversible thrombocytopenia.
Infections
Rituximab monotherapy (for 4 weeks)
Rituximab causes B-cell depletion in 70–80% of patients and a decrease in serum immunoglobulin concentrations in a small number of patients. Bacterial, viral, fungal infections and infections of unspecified etiology (all, regardless of cause) develop in 30.3% of patients. Severe infections (grade 3 and 4), including sepsis, were noted in 3.9% of patients.
Maintenance therapy (non-Hodgkin's lymphoma) up to 2 years
During rituximab therapy, an increase in the overall incidence of infections was observed, incl. infections of 3 - 4 degrees of severity. There was no increase in the incidence of infectious complications with maintenance therapy lasting 2 years.
Cases of progressive multifocal leukoencephalopathy (PML)
with a fatal outcome in patients with non-Hodgkin's lymphoma after disease progression and re-treatment.
Rituximab in combination with chemotherapy according to the following regimens: R-CVP
- for non-Hodgkin's lymphoma;
R-CHOP
- for diffuse large B-cell non-Hodgkin lymphoma;
R-FC
- for chronic lymphocytic leukemia
During rituximab therapy according to the R-CVP
no increase in the incidence of infections or infestations was observed.
The most common infections were upper respiratory tract infections (12.3% in the R-CVP
).
Serious infections occurred in 4.3% of patients receiving R-CVP
;
No life-threatening infections were reported. The proportion of patients with grade 2–4 infections and/or febrile neutropenia in the R-CHOP
was 55.4%.
The overall rate of grade 2–4 infections in the R-CHOP
was 45.5%.
The frequency of fungal infections of 2–4 degrees of severity in the R-CHOP
was higher than in
the CHOP
due to a higher frequency of local candidiasis and amounted to 4.5%.
The incidence of grade 2–4 herpes infection was higher in the R-CHOP
than in
the CHOP
and amounted to 4.5%.
In patients with chronic lymphocytic leukemia, the incidence of hepatitis B (exacerbation and primary infection) of grade 3–4 in the R-FC
amounted to 2%.
From the blood system
Monotherapy with rituximab (for 4 weeks)
Severe thrombocytopenia (grade 3 and 4) was observed in 1.7% of patients, severe neutropenia - in 4.2% of patients, and severe anemia (grade 3 and 4) - in 1. 1% of patients.
Maintenance therapy (non-Hodgkin's lymphoma) up to 2 years
Leukopenia (grades 3 and 4) was observed in 5% of patients and neutropenia (grades 3 and 4) in 10% of patients receiving rituximab. The incidence of thrombocytopenia (grade 3–4) was low and was <1%.
Approximately 50% of patients for whom B-cell recovery data were available took 12 months or more to recover B-cell counts to normal levels after completion of rituximab induction therapy.
Rituximab in combination with chemotherapy according to the following regimens: R-CVP
- for non-Hodgkin's lymphoma;
R-CHOP
- for diffuse large B-cell non-Hodgkin lymphoma;
R-FC
- for chronic lymphocytic leukemia
Severe neutropenia and leukopenia:
In patients receiving rituximab in combination with chemotherapy, grade 3 and 4 leukopenia were observed more often than in patients receiving chemotherapy alone.
The incidence of severe leukopenia was 88% in patients receiving R-CHOP
and 23% in patients receiving
R-FC
.
The incidence of severe neutropenia was 24% in the R-CVP
, 97% in the
R-CHOP
, and 30% in the
R-FC
in previously untreated chronic lymphocytic leukemia.
The higher incidence of neutropenia in patients receiving rituximab and chemotherapy was not associated with an increased incidence of infections and infestations compared with patients receiving chemotherapy alone. In patients with recurrent or chemoresistant chronic lymphocytic leukemia after treatment according to the R-FC
, in some cases, neutropenia was characterized by a long course and later manifestations.
Severe anemia and thrombocytopenia (grade 3 and 4):
There was no significant difference in the frequency of anemia of the 3rd and 4th severity in the groups.
In the R-FC
, in the first line of treatment for chronic lymphocytic leukemia, anemia of the 3rd and 4th severity was found in 4% of patients, thrombocytopenia of the 3rd and 4th severity - in 7% of patients.
In the R-FC
with recurrent or chronic lymphocytic leukemia, anemia of the 3rd and 4th severity occurred in 12% of patients, thrombocytopenia of the 3rd and 4th severity - in 11% of patients.
From the SSS side
Rituximab monotherapy (for 4 weeks)
Side effects from the cardiovascular system were noted in 18.8%. The most common occurrences are increases and decreases in blood pressure. In isolated cases, cardiac arrhythmias of the 3rd and 4th degree of severity (including ventricular and supraventricular tachycardia) and angina pectoris were observed.
Maintenance therapy (non-Hodgkin's lymphoma) up to 2 years
The incidence of grade 3 and 4 cardiovascular events was similar in patients receiving rituximab and those not receiving it. Serious cardiovascular events occurred in less than 1% of patients not receiving rituximab and in 3% of patients receiving the drug (atrial fibrillation - 1%, myocardial infarction - 1%, left ventricular failure - <1%, myocardial ischemia - y <1%).
Rituximab in combination with chemotherapy according to the following regimens: R-CVP
- for non-Hodgkin's lymphoma;
R-CHOP
- for diffuse large B-cell non-Hodgkin lymphoma;
R-FC
- for chronic lymphocytic leukemia
Frequency of heart rhythm disturbances of the 3rd and 4th severity, mainly supraventricular arrhythmias (tachycardia, flutter and atrial fibrillation), in the R-CHOP
was higher and amounted to 6.9%.
All arrhythmias developed either in connection with rituximab infusion or were associated with predisposing conditions such as fever, infection, acute myocardial infarction, or concomitant diseases of the respiratory system and cardiovascular system. The R-CHOP
and
CHOP
groups did not differ in the incidence of other grade 3 and 4 cardiac adverse events, including heart failure, myocardial disease, and manifestations of coronary artery disease.
The overall incidence of grade 3 and 4 cardiovascular events was low as in first-line treatment for chronic lymphocytic leukemia (4% in the R-FC
), and in the treatment of recurrent/chemoresistant chronic lymphocytic leukemia (4% in the
R-FC
).
Nervous system
Rituximab in combination with chemotherapy according to the following regimens: R-CVP
for non-Hodgkin's lymphoma;
R-CHOP
for diffuse large B-cell non-Hodgkin lymphoma;
R-FC
for chronic lymphocytic leukemia
In patients (2%) from the R-CHOP
with cardiovascular risk factors developed cerebroembolic events during the first cycle of therapy, in contrast to patients in the
CHOP
who developed cerebroembolic events during the observation period without treatment. There was no difference between groups in the incidence of other thromboembolism.
The overall incidence of grade 3 and 4 neurological impairment was low as in first-line therapy for chronic lymphocytic leukemia (4% in the R-FC
), and in the treatment of recurrent/chemoresistant chronic lymphocytic leukemia (3% in the
R-FC
).
IgG concentration
Maintenance therapy (non-Hodgkin's lymphoma) up to 2 years
After induction therapy, IgG
was below the lower limit of normal (<7 g/l) in the group receiving rituximab and in the group not receiving the drug.
In the group not receiving rituximab, the median IgG
consistently increased and exceeded the lower limit of normal, while the median
IgG
did not change in the group receiving rituximab.
In 60% of patients receiving rituximab for 2 years, IgG
remained below the lower limit.
In the group without rituximab therapy, IgG
remained below the lower limit in 36% of patients after 2 years.
Special categories of patients
Rituximab monotherapy (for 4 weeks)
Old age (≥65 years):
the frequency and severity of all adverse reactions and grade 3 and 4 adverse reactions did not differ from those in younger patients.
Combination therapy
Old age (65 years and older):
in first-line therapy, as well as in the treatment of relapsed/chemoresistant chronic lymphocytic leukemia, the incidence of grade 3 and 4 side effects from the blood and lymphatic system was higher compared to younger patients.
High tumor load (diameter of single lesions more than 10 cm):
the frequency of adverse reactions of the 3rd and 4th severity is increased.
Repeat therapy:
the frequency and severity of adverse reactions does not differ from those during initial therapy.
Information on the post-registration use of rituximab for non-Hodgkin's lymphoma and chronic lymphocytic leukemia
From the SSS side:
severe cardiovascular events associated with infusion reactions, such as heart failure and myocardial infarction, mainly in patients with a history of cardiovascular disease and/or receiving cytotoxic chemotherapy; very rarely - vasculitis, mainly cutaneous (leukocytoclastic).
From the respiratory system:
respiratory failure and pulmonary infiltrates caused by infusion reactions; In addition to pulmonary adverse events due to infusion reactions, interstitial lung disease, in some cases fatal, has been observed.
From the circulatory and lymphatic system:
reversible acute thrombocytopenia associated with infusion reactions.
From the skin and its appendages:
rarely - severe bullous reactions, toxic epidermal necrolysis and Stevens-Johnson syndrome, in some cases with death.
From the nervous system:
rarely - neuropathy of the cranial nerves in combination with peripheral neuropathy or without it (marked decrease in visual acuity, hearing, damage to other sensory organs, paresis of the facial nerve) during various periods of therapy up to several months after completion of the course of treatment with rituximab.
Cases of posterior reversible encephalopathy ( PRES
)/posterior reversible leukoencephalopathy syndrome (
PRLS
) have been reported in patients treated with rituximab. Symptoms included blurred vision, headache, seizures and mental disturbances, with or without increased blood pressure.
Confirm diagnosis of PRES/PRLS
possible using brain imaging techniques.
In the cases described, patients had risk factors for developing PRES/PRLS
, such as underlying disease, hypertension, immunosuppressive therapy and/or chemotherapy.
From the body as a whole, reactions at the injection site:
rarely - serum sickness.
Infections:
reactivation of viral hepatitis B (in most cases with a combination of rituximab and cytotoxic chemotherapy);
as well as other severe viral infections (primary infection, viral reactivation or exacerbation), some of which were fatal, caused by cytomegalovirus, Varicella zoster
,
Herpes simplex
JC
polyomavirus (
PML
), hepatitis C virus.
From the gastrointestinal tract:
perforation of the stomach and/or intestines (possibly fatal) when rituximab is combined with chemotherapy for non-Hodgkin's lymphoma.
From the blood and lymphatic system:
rarely - neutropenia that occurred 4 weeks after the last administration of rituximab;
a transient increase in IgM
in patients with Waldenström's macroglobulinemia, followed by a return to its original value after 4 months.
Indications
- Non-Hodgkin's lymphoma. The drug is used if chemotherapy does not produce treatment results, or if a relapse occurs;
- Follicular lymphoma (at the third or fourth stage). In this case, a mandatory condition for treatment is a combination with chemotherapy;
- As a maintenance therapy in the treatment of follicular lymphoma (after the body responds to induction therapy);
- For chronic lymphocytic leukemia. Used for chemotherapy-resistant forms, for relapses, in combination with chemotherapy;
- Rheumatoid arthritis (severe and moderate). Used in combination with methotrexate;
- Granulomatosis.
Acellbia®
To assess the frequency of adverse reactions, the following criteria are used: very often > 10%, often > 1% - < 10%, infrequently > 0.1% - < 1%.
Rituximab in the treatment of low-grade or follicular non-Hodgkin lymphoma - monotherapy/maintenance therapy.
Adverse reactions were reported up to 12 months after monotherapy and up to 1 month after rituximab maintenance therapy.
Infectious and parasitic diseases: very common
- bacterial and viral infections;
often -
respiratory tract infections*, pneumonia*, sepsis, herpes zoster*, infections accompanied by fever*, fungal infections, infections of unknown etiology.
Blood and lymphatic system disorders: very common
- leukopenia, neutropenia;
often -
thrombocytopenia, anemia;
uncommon
- lymphadenopathy, bleeding disorder, transient partial aplastic anemia, hemolytic anemia.
Disorders of the respiratory system, chest and mediastinal organs: often -
rhinitis, bronchospasm, cough, respiratory diseases, shortness of breath, chest pain;
uncommon
- hypoxia, impaired pulmonary function, bronchiolitis obliterans, bronchial asthma.
Immune system disorders:
very often - angioedema; often - hypersensitivity reactions.
Metabolic and nutritional disorders:
often - hyperglycemia, weight loss, peripheral edema, facial edema, increased LDH activity, hypocalcemia.
General disorders and disorders at the injection site: very often -
headache, fever, chills, asthenia;
often -
pain in tumor foci, flu-like syndrome, hot flashes, weakness;
Uncommon:
pain at the injection site.
Gastrointestinal disorders: very common -
nausea;
often -
vomiting, diarrhea, dyspepsia, lack of appetite, dysphagia, stomatitis, constipation, abdominal pain, sore throat; infrequently - abdominal enlargement.
Cardiovascular system disorders: often -
decreased blood pressure, increased blood pressure, orthostatic hypotension, tachycardia, arrhythmia, atrial fibrillation*, cardiac pathology*;
uncommon -
left ventricular heart failure*, ventricular and supraventricular tachycardia*, bradycardia, myocardial ischemia*, angina*.
Nervous system disorders: often -
dizziness, paresthesia, hypoesthesia, sleep disturbance, anxiety, agitation, vasodilation;
infrequently -
perversion of taste.
Mental disorders: uncommon -
nervousness, depression.
Musculoskeletal and connective tissue disorders: common
- myalgia, arthralgia, muscle hypertonicity, back pain, neck pain, pain.
Disorders of the skin and subcutaneous tissues: very often -
itching, rash;
often -
urticaria, increased sweating at night, sweating, alopecia*.
Visual disturbances: often
- lacrimation disorders, conjunctivitis.
Hearing and labyrinthine disorders
: often - pain and tinnitus.
Laboratory and instrumental data: very often -
a decrease in the level of immunoglobulins G (IgG).
* - frequency is indicated only for adverse reactions > 3 severity in accordance with the toxicity criteria of the National Cancer Institute (NCI-CTC).
Rituximab in combination with chemotherapy
( R - CHOP , R - CVP , R - FC ) for non-Hodgkin's lymphoma and chronic lymphocytic leukemia
The following are severe adverse reactions in addition to those observed with monotherapy/maintenance therapy and/or occurring at a higher frequency.
Infectious and parasitic diseases: very often -
bronchitis;
often -
acute bronchitis, sinusitis, hepatitis B* (exacerbation and primary infection).
Blood and lymphatic system disorders: very common -
neutropenia**, febrile neutropenia, thrombocytopenia;
often -
pancytopenia, granulocytopenia.
Skin and subcutaneous tissue disorders: very common -
alopecia;
often -
skin diseases.
General disorders and disorders at the injection site: often -
fatigue, chills. * — frequency is indicated based on observations during the treatment of relapsed/chemoresistant chronic lymphocytic leukemia according to the R-FC regimen.
**prolonged and/or delayed neutropenia has been observed after completion of R-FC therapy in previously untreated patients or in patients with relapsed/chemoresistant chronic lymphocytic leukemia.
The following are adverse events that occurred with the same frequency (or less frequently) during rituximab therapy compared to the control group: hematotoxicity, neutropenic infections, urinary tract infections, septic shock, pulmonary superinfections, implant infections, staphylococcal septicemia, mucous nasal discharge, edema lungs, heart failure, sensitivity disorders, venous thrombosis, incl. deep vein thrombosis of the extremities, mucositis, edema of the lower extremities, decreased left ventricular ejection fraction, increased temperature, deterioration of general health, bacteremia, multiple organ failure, decompensation of diabetes mellitus.
The safety profile of rituximab in combination with chemotherapy regimens MCP, CHVP-IFN does not differ from that in combination with CVP, CHOP or FC in relevant populations.
Infusion reactions
Rituximab monotherapy (for 4 weeks)
More than 50% of patients experienced events resembling infusion reactions, most often during the first infusions. Infusion reactions include chills, trembling, weakness, shortness of breath, nausea, rash, hot flashes, low blood pressure, fever, itching, urticaria, irritation of the tongue or swelling of the larynx (angioedema), rhinitis, vomiting, pain in tumor areas, headache, bronchospasm. The development of signs of tumor lysis syndrome has been reported.
Rituximab in combination with chemotherapy according to the following regimens:
R - CVP for non-Hodgkin's lymphoma; R - CHOP for diffuse large B-cell non-Hodgkin's lymphoma; R - FC in chronic lymphocytic leukemia
Grade 3 and 4 infusion reactions during infusion or within 24 hours after rituximab infusion were observed during the first cycle of chemotherapy in 12% of patients.
The incidence of infusion reactions decreased with each subsequent cycle and by the 8th cycle of chemotherapy, the incidence of infusion reactions decreased to less than 1%. Infusion reactions in addition to those mentioned above (with rituximab monotherapy) included: dyspepsia, rash, increased blood pressure, tachycardia, signs of tumor lysis syndrome, in some cases - myocardial infarction, atrial fibrillation, pulmonary edema and acute reversible thrombocytopenia.
Infections
Rituximab monotherapy (for 4 weeks)
Rituximab causes depletion of the B cell pool in 70-80% of patients and a decrease in serum immunoglobulin concentrations in a small number of patients. Bacterial, viral, fungal infections and infections of unspecified etiology (all, regardless of cause) develop in 30.3% of patients. Severe infections (grades 3 and 4), including sepsis, were noted in 3.9% of patients.
Maintenance therapy (non-Hodgkin's lymphoma) up to 2 years
An increase in the overall incidence of infections, including grade 3-4 infections, was observed with rituximab therapy. There was no increase in the incidence of infectious complications with maintenance therapy lasting 2 years.
Fatal progressive multifocal leukoencephalopathy (PML) has been reported in patients with non-Hodgkin's lymphoma after disease progression and re-treatment.
Rituximab in combination with chemotherapy according to the following regimens:
R - CVP for non-Hodgkin's lymphoma; R - CHOP for diffuse B-cell non-Hodgkin's lymphoma; R - FC in chronic lymphocytic leukemia
There was no increase in the incidence of infections or invasions with rituximab therapy according to the R-CVP regimen. Upper respiratory tract infections were the most common (12.3% in the R-CVP group). Serious infections occurred in 4.3% of patients receiving R-CVP chemotherapy; No life-threatening infections were reported. The proportion of patients with grade 2-4 infections and/or febrile neutropenia in the R-CHOP group was 55.4%. The overall incidence of grade 2–4 infections in the R-CHOP group was 45.5%. The incidence of grade 2-4 fungal infections in the R-CHOP group was higher than in the CHOP group due to a higher incidence of local candidiasis and amounted to 4.5%. The incidence of grade 2-4 herpes infection was higher in the R-CHOP group than in the CHOP group and was 4.5%.
In patients with chronic lymphocytic leukemia, the incidence of hepatitis B (exacerbation and primary infection) of grade 3-4 in the R-FC group was 2%
From the blood system
Pituximab monotherapy (for 4 weeks)
Severe thrombocytopenia (grade 3 and 4) was observed in 1.7% of patients, severe neutropenia - in 4.2% of patients, and severe anemia (grade 3 and 4) - in 1.1% of patients.
Maintenance therapy (non-Hodgkin's lymphoma) up to 2 years
Leukopenia (grades 3 and 4) was observed in 5% of patients, and neutropenia (grades 3 and 4) in 10% of patients receiving rituximab. The incidence of thrombocytopenia (grade 3-4 severity) was low and amounted to <1%.
Approximately 50% of patients for whom B-cell recovery data were available took 12 months or more to recover B-cell counts to normal levels after completion of rituximab induction therapy.
Rituximab in combination with chemotherapy according to the following regimens:
R - CVP for Hodgkin's lymphoma; R — CHOP for diffuse large B-cell non-Hodgkin lymphoma; R - FC in chronic lymphocytic leukemia
Severe neutropenia and leukopenia:
in patients receiving rituximab in combination with chemotherapy, leukopenia of grades 3 and 4 was observed more often compared to patients receiving chemotherapy alone. The incidence of severe leukopenia was 88% in patients receiving R-CHOP and 23% in patients receiving R-FC. The incidence of severe neutropenia was 24% in the R-CVP group, 97% in the R-CHOP group, and 30% in the R-FC group in previously untreated chronic lymphocytic leukemia. The higher incidence of neutropenia in patients receiving rituximab and chemotherapy was not associated with an increased incidence of infections and infestations compared with patients receiving chemotherapy alone. In patients with recurrent or chemoresistant chronic lymphocytic leukemia after treatment according to the R-FC regimen, in some cases, neutropenia was characterized by a long course and later manifestations.
Severe anemia and thrombocytopenia (grades 3 and 4):
There was no significant difference in the incidence of anemia of grades 3 and 4 in the groups. In the R-FC group, in the first line of treatment for chronic lymphocytic leukemia, anemia of grades 3 and 4 occurred in 4% of patients, thrombocytopenia of grades 3 and 4 - in 7% of patients. In the R-FC group with recurrent or chronic lymphocytic leukemia, anemia of grades 3 and 4 occurred in 12% of patients, thrombocytopenia of grades 3 and 4 - in 11% of patients.
From the cardiovascular system
Rituximab monotherapy (for 4 weeks)
Side effects from the cardiovascular system were noted in 18.8%. The most common are increased and decreased blood pressure. In isolated cases, cardiac arrhythmias of grade 3 and 4 were observed (including ventricular and supraventricular tachycardia) and angina pectoris.
Maintenance therapy (non-Hodgkin's lymphoma) up to 2 years
The incidence of grade 3 and 4 cardiovascular events was similar in patients receiving rituximab and those not receiving it. Serious cardiovascular events occurred in less than 1% of patients not receiving rituximab and in 3% of patients receiving the drug (atrial fibrillation in 1%, myocardial infarction in 1%, left ventricular failure in <1%, myocardial ischemia in <1% ).
Rituximab in combination with chemotherapy according to the following regimens:
R - CVP for non-Hodgkin's lymphoma; R — CHOP for diffuse large B-cell Pehodgkin lymphoma; R - FC in chronic lymphocytic leukemia
The frequency of heart rhythm disturbances of grade 3 and 4, mainly supraventricular arrhythmias (tachycardia, atrial flutter and fibrillation), was higher in the R-CHOP group and amounted to 6.9%. All arrhythmias developed either in connection with rituximab infusion or were associated with predisposing conditions such as fever, infection, acute myocardial infarction, or concomitant diseases of the respiratory and cardiovascular systems. The R-CHOP and CHOP groups did not differ in the incidence of other grade 3 and 4 cardiac adverse events, including heart failure, myocardial disease, and manifestation of coronary artery disease.
The overall incidence of grade 3 and 4 cardiovascular events was low both in first-line treatment of chronic lymphocytic leukemia (4% in the R-FC group) and in the treatment of relapsed/chemoresistant chronic lymphocytic leukemia (4% in the R-FC group).
Nervous system
Rituximab in combination with chemotherapy according to the following regimens:
R - CVP for non-Hodgkin's lymphoma; R — CHOP for diffuse large B-cell non-Hodgkin lymphoma; R - FC in chronic lymphocytic leukemia
Patients (2%) in the R-CHOP group with cardiovascular risk factors developed thromboembolic cerebrovascular accidents during the first cycle of therapy, in contrast to patients in the CHOP group who developed cerebrovascular accidents during observation without treatment. There was no difference between groups in the incidence of other thromboembolism.
The overall incidence of grade 3 and 4 neurological impairment was low both in the first-line treatment of chronic lymphocytic leukemia (4% in the R-FC group) and in the treatment of relapsed/chemoresistant chronic lymphocytic leukemia (3% in the R-FC group).
IgG
concentration Maintenance therapy (non-Hodgkin's lymphoma) up to 2 years
After induction therapy, IgG concentrations were below the lower limit of normal (<7 g/L) in the rituximab-treated and non-rituximab groups. In the group not receiving rituximab, the median IgG level consistently increased and exceeded the lower limit of normal, while the median IgG level did not change in the group receiving rituximab. In 60% of patients receiving rituximab for 2 years, IgG levels remained below the lower limit. In the group without rituximab therapy, IgG levels remained below the lower limit in 36% of patients after 2 years.
Special categories of patients
Rituximab monotherapy (for 4 weeks)
Elderly age
(>65 years): frequency and severity of all adverse reactions and
grade 3 and 4 adverse reactions are no different from those in younger patients.
Combination therapy
Elderly age
(65 years and older): In first-line therapy and in treatment of relapsed/chemoresistant chronic lymphocytic leukemia, the incidence of grade 3 and 4 hematopoietic and lymphatic adverse events was higher compared to younger patients.
High tumor burden
(diameter of single lesions more than 10 cm): increased frequency of adverse reactions of grade 3 and 4.
Repeat therapy
: the frequency and severity of adverse reactions do not differ from those during initial therapy.
Information on the post-registration use of rituximab for non-Hodgkin's lymphoma and chronic lymphocytic leukemia
From the cardiovascular system:
severe cardiovascular events associated with infusion reactions, such as heart failure and myocardial infarction, mainly in patients with a history of cardiovascular disease and/or receiving cytotoxic chemotherapy;
very rarely
- vasculitis, mainly cutaneous (leukocytoclastic).
From the respiratory system:
respiratory failure and pulmonary infiltrates caused by infusion reactions; In addition to pulmonary adverse events due to infusion reactions, interstitial lung disease, in some cases fatal, has been observed.
From the circulatory and lymphatic system:
reversible acute thrombocytopenia associated with infusion reactions.
From the skin and its appendages: rarely
- severe bullous reactions, toxic epidermal necrolysis and Stevens-Johnson syndrome, in some cases fatal.
From the nervous system: rarely -
neuropathy of the cranial nerves in combination with peripheral neuropathy or without it (marked decrease in visual acuity, hearing, damage to other sensory organs, paresis of the facial nerve) during various periods of therapy up to several months after completion of treatment with rituximab. Cases of posterior reversible encephalopathy (P11E8)/posterior reversible leukoencephalopathy syndrome (PRLS) have been reported in patients treated with rituximab. Symptoms included blurred vision, headache, seizures and mental disturbances, with or without increased blood pressure. The diagnosis of PRES/PRLS can be confirmed using brain imaging techniques. In the cases described, patients had risk factors for developing PRES/PRLS, such as underlying disease, elevated blood pressure, immunosuppressive therapy and/or chemotherapy.
From the body as a whole, reactions at the injection site: rare
- serum sickness.
Infections:
reactivation of viral hepatitis B (in most cases with a combination of rituximab and cytotoxic chemotherapy); as well as other severe viral infections (primary infection, viral reactivation or exacerbation), some of which were fatal, caused by cytomegalovirus, Varicella zoster, Herpes simplex, JC polyomavirus (PML), hepatitis C virus.
When rituximab was prescribed for indications not covered by the instructions for medical use, sarcoma progression was observed in patients with previously diagnosed Kaposi's sarcoma (most patients were HIV-positive).
From the gastrointestinal tract:
perforation of the stomach and/or intestines (possibly fatal) when rituximab is combined with chemotherapy for non-Hodgkin's lymphoma.
From the blood and lymphatic system: rarely -
neutropenia occurring 4 weeks after the last administration of rituximab; a transient increase in IgM levels in patients with Waldenström's macroglobulinemia, followed by a return to its original value after 4 months.
Side effects
Viral and bacterial infections, respiratory tract damage, sepsis, herpes, and pneumonia often occur. Infections often occur with an increase in body temperature. Fungal infections may appear. Leukopenia and anemia occur very often. Less common are problems with blood clotting and hemolytic anemia. Rhinitis, cough, bronchospasms, respiratory diseases, and chest pain often occur. Less commonly – hypoxia, impaired lung function, bronchial asthma.
Angioedema appears, sensitivity increases, and allergic reactions may occur. Weight decreases, facial swelling and peripheral edema, hyperglycemia, increased or decreased blood pressure occur.
Acellbia
To assess the frequency of adverse reactions, the following criteria are used: very often >10%, often >1% - 0.1% -
Rituximab for the treatment of low-grade or follicular non-Hodgkin lymphoma - monotherapy/maintenance therapy
Adverse reactions were reported up to 12 months after monotherapy and up to 1 month after rituximab maintenance therapy.
Infectious and parasitic diseases: very often - bacterial and viral infections; often - respiratory tract infections*, pneumonia*, sepsis, herpes zoster*, infections accompanied by fever*, fungal infections, infections of unknown etiology.
Disorders of the blood and lymphatic system: very often - leukopenia, neutropenia; often - thrombocytopenia, anemia; uncommon - lymphadenopathy, bleeding disorder, transient partial aplastic anemia, hemolytic anemia.
Disorders of the respiratory system, chest and mediastinal organs: often - rhinitis, brochospasm, cough, respiratory diseases, shortness of breath, chest pain; uncommon - hypoxia, impaired pulmonary function, bronchiolitis obliterans, bronchial asthma.
Immune system disorders: very often - angioedema; often - hypersensitivity reactions.
Metabolic and nutritional disorders: often - hyperglycemia, weight loss, peripheral edema, facial edema, increased LDH activity, hypocalcemia.
General disorders and disorders at the injection site: very often - headache, fever, chills, asthenia; often - pain in tumor foci, flu-like syndrome, hot flashes, weakness; Uncommon: pain at the injection site.
Gastrointestinal disorders: very often - nausea; often - vomiting, diarrhea, dyspepsia, lack of appetite, dysphagia, stomatitis, constipation, abdominal pain, sore throat; infrequently - abdominal enlargement.
Disorders of the cardiovascular system: often - decreased blood pressure, increased blood pressure, orthostatic hypotension, tachycardia, arrhythmia, atrial fibrillation*, cardiac pathology*; uncommon - left ventricular heart failure*, ventricular and supraventricular tachycardia*, bradycardia, myocardial ischemia*, angina*.
Nervous system disorders: often - dizziness, paresthesia, hypoesthesia, sleep disturbance, anxiety, agitation, vasodilation; infrequently - perversion of taste.
Mental disorders: infrequently - nervousness, depression.
Musculoskeletal and connective tissue disorders: often - myalgia, arthralgia, muscle hypertonicity, back pain, neck pain, pain.
Disorders of the skin and subcutaneous tissues: very often - itching, rash; often - urticaria, increased sweating at night, sweating, alopecia*.
Visual disturbances: often - lacrimation disorders, conjunctivitis.
Hearing and labyrinthine disorders: often - pain and tinnitus.
Laboratory and instrumental data: very often - a decrease in the level of immunoglobulins G (IgG).
* - frequency is indicated only for adverse reactions of grade 3 in accordance with the toxicity criteria of the National Cancer Institute (NCI-CTC).
Rituximab in combination with chemotherapy (R-CHOP, R-CVP, R-FC) for non-Hodgkin's lymphoma and chronic lymphocytic leukemia
The following are severe adverse reactions in addition to those observed with monotherapy/maintenance therapy and/or occurring at a higher frequency.
Infectious and parasitic diseases: very often - bronchitis; often - acute bronchitis, sinusitis, hepatitis B* (exacerbation and primary infection).
Disorders of the blood and lymphatic system: very often - neutropenia**, febrile neutropenia, thrombocytopenia; often - pancytopenia, granulocytopenia.
Disorders of the skin and subcutaneous tissues: very often - alopecia; often - skin diseases.
General disorders and disorders at the injection site: often - fatigue, chills.
* — frequency is indicated based on observations during the treatment of recurrent/chemoresistant chronic lymphocytic leukemia according to the R-FC regimen.
** - prolonged and/or delayed neutropenia was observed after completion of R-FC therapy in previously untreated patients or in patients with relapsed/chemoresistant chronic lymphocytic leukemia.
The following are adverse events that occurred with the same frequency (or less frequently) during rituximab therapy compared to the control group: hematotoxicity, neutropenic infections, urinary tract infections, septic shock, pulmonary superinfections, implant infections, staphylococcal septicemia, mucous nasal discharge, edema lungs, heart failure, sensory disturbances, venous thrombosis, including deep vein thrombosis of the extremities, mucositis, edema of the lower extremities, decreased left ventricular ejection fraction, increased temperature, deterioration of general health, bacteremia, multiple organ failure, decompensation of diabetes mellitus.
The safety profile of rituximab in combination with chemotherapy regimens MCP, CHVP-IFN does not differ from that when the drug is combined with CVP, CHOP or FC in relevant populations.
Infusion reactions
Rituximab monotherapy (for 4 weeks)
More than 50% of patients experienced events resembling infusion reactions, most often during the first infusions. Infusion reactions include chills, trembling, weakness, shortness of breath, nausea, rash, hot flashes, low blood pressure, fever, itching, urticaria, irritation of the tongue or swelling of the larynx (angioedema), rhinitis, vomiting, pain in tumor areas, headache, bronchospasm. The development of signs of tumor lysis syndrome has been reported.
Rituximab in combination with chemotherapy according to the following regimens: K-CVP for non-Hodgkin's lymphoma; R-CHOP for diffuse large B-cell non-Hodgkin lymphoma: R-FC for chronic lymphocytic leukemia
Grade 3 and 4 infusion reactions during infusion or within 24 hours after rituximab infusion were observed during the first cycle of chemotherapy in 12% of patients.
The incidence of infusion reactions decreased with each subsequent cycle and by the 8th cycle of chemotherapy, the incidence of infusion reactions decreased to less than 1%. Infusion reactions in addition to those mentioned above (with rituximab monotherapy) included: dyspepsia, rash, increased blood pressure, tachycardia, signs of tumor lysis syndrome, in some cases - myocardial infarction, atrial fibrillation, pulmonary edema and acute reversible thrombocytopenia.
Infections
Rituximab monotherapy (for 4 weeks)
Rituximab causes depletion of the B cell pool in 70-80% of patients and a decrease in serum immunoglobulin concentrations in a small number of patients. Bacterial, viral, fungal infections and infections of unspecified etiology (weight, regardless of cause) develop in 30.3% of patients. Severe infections (grades 3 and 4), including sepsis, were noted in 3.9% of patients.
Maintenance therapy (non-Hodgkin's lymphoma) up to 2 years
An increase in the overall incidence of infections, including grade 3-4 infections, was observed with rituximab therapy. There was no increase in the incidence of infectious complications with maintenance therapy lasting 2 years.
Fatal progressive multifocal leukoencephalopathy (PML) has been reported in patients with non-Hodgkin's lymphoma after disease progression and re-treatment.
Rituximab in combination with chemotherapy according to the following regimens: R-CVP for non-Hodgkin's lymphoma; R-CHOP for diffuse large B-cell non-Hodgkin lymphoma; R-FC for chronic lymphocytic leukemia
There was no increase in the incidence of infections or infestations with rituximab R-CVP regimen. Upper respiratory tract infections were the most common (12.3% in the R-CVP group). Serious infections occurred in 4.3% of patients receiving R-CVP chemotherapy; No life-threatening infections were reported. The proportion of patients with grade 2-4 infections and/or febrile neutropenia in the R-CHOP group was 55.4%. The total incidence of grade 2-4 infections in the R-CHOP group was 45.5%. The frequency of fungal infections of grade 2-4 in the R-CHOP group was higher than in the CHOP group due to a higher frequency of local candidiasis and amounted to 4.5%. The incidence of grade 2-4 herpes infection was higher in the R-CHOP group than in the CHOP group and was 4.5%.
In patients with chronic lymphocytic leukemia, the incidence of hepatitis B (exacerbation and primary infection) of grade 3-4 severity in the R-FC group was 2%.
From the blood system
Rituximab monotherapy (for 4 weeks)
Severe thrombocytopenia (grades 3 and 4) was observed in 1.7% of patients, severe neutropenia - in 4.2% of patients, and severe anemia (grades 3 and 4) - in 1.1% of patients.
Maintenance therapy (non-Hodgkin's lymphoma) up to 2 years
Leukopenia (grades 3 and 4) was observed in 5% of patients, and neutropenia (grades 3 and 4) in 10% of patients receiving rituximab. The incidence of thrombocytopenia (grade 3-4) was low and amounted to
Approximately 50% of patients for whom B-cell recovery data were available took 12 months or more to recover B-cell counts to normal levels after completion of rituximab induction therapy.
Rituximab in combination with chemotherapy according to the following regimens: R-CVP for non-Hodgkin's lymphoma; R-CHOP for diffuse large B-cell non-Hodgkin lymphoma; R-FC for chronic lymphocytic leukemia
Severe neutropenia and leukopenia: In patients receiving rituximab in combination with chemotherapy, grades 3 and 4 leukopenia were observed more often than in patients receiving chemotherapy alone. The incidence of severe leukopenia was 88% in patients receiving R-CHOP and 23% in patients receiving R-FC. The incidence of severe neutropenia was 24% in the R-CVP group, 97% in the R-CHOP group, and 30% in the R-FC group in previously untreated chronic lymphocytic leukemia. The higher incidence of neutropenia in patients receiving rituximab and chemotherapy was not associated with an increased incidence of infections and infestations compared with patients receiving chemotherapy alone. In patients with recurrent or chemoresistant chronic lymphocytic leukemia after treatment according to the R-FC regimen, in some cases, neutropenia was characterized by a long course and later manifestations.
Severe anemia and thrombocytopenia (grades 3 and 4): there was no significant difference in the incidence of anemia of grades 3 and 4 between groups. In the R-FC group, in the first line of treatment for chronic lymphocytic leukemia, anemia of grades 3 and 4 occurred in 4% of patients, thrombocytopenia of grades 3 and 4 - in 7% of patients. In the R-FC group with recurrent or chronic lymphocytic leukemia, anemia of grades 3 and 4 occurred in 12% of patients, thrombocytopenia of grades 3 and 4 - in 11% of patients.
From the cardiovascular system
Rituximab monotherapy (for 4 weeks)
Side effects from the cardiovascular system were noted in 18.8%. The most common are increased and decreased blood pressure. In isolated cases, cardiac arrhythmias of grade 3 and 4 were observed (including ventricular and supraventricular tachycardia) and angina pectoris.
Maintenance therapy (non-Hodgkin's lymphoma) up to 2 years
The incidence of grade 3 and 4 cardiovascular events was similar in patients receiving rituximab and those not receiving it. Serious cardiovascular events occurred in less than 1% of patients not receiving rituximab and in 3% of patients receiving the drug (atrial fibrillation in 1%, myocardial infarction in 1%, left ventricular failure in
Rituximab and combinations with chemotherapy according to the following regimens: R-CVP for non-Hodgkin's lymphoma; R-CHOP for diffuse large B-cell non-Hodgkin lymphoma; R-FC for chronic lymphocytic leukemia
The incidence of grade 3 and 4 cardiac arrhythmias, mainly supraventricular arrhythmias (tachycardia, atrial flutter and atrial fibrillation), was higher in the R-CHOP group and amounted to 6.9%. All arrhythmias developed either in connection with rituximab infusion or were associated with predisposing conditions such as fever, infection, acute myocardial infarction, or concomitant diseases of the respiratory and cardiovascular systems. The R-CHOP and CHOP groups did not differ in the incidence of other grade 3 and 4 cardiac adverse events, including heart failure, myocardial disease, and manifestation of coronary artery disease.
The overall incidence of grade 3 and 4 cardiovascular events was low both in first-line treatment of chronic lymphocytic leukemia (4% in the R-FC group) and in the treatment of relapsed/chemoresistant chronic lymphocytic leukemia (4% in the R-FC group).
Nervous system
Rituximab in combination with chemotherapy according to the following regimens: R-CVP for non-Hodgkin's lymphoma; R-CHOP for diffuse large B-cell non-Hodgkin lymphoma; R-FC for chronic lymphocytic leukemia
Patients (2%) in the R-CHOP group with cardiovascular risk factors developed cerebroembolic events during the first cycle of therapy, in contrast to patients in the CHOP group who developed cerebroembolic events during the observation period without treatment. There was no difference between groups in the incidence of other thromboembolism.
The overall incidence of grade 3 and 4 neurological impairment was low both in the first-line treatment of chronic lymphocytic leukemia (4% in the R-FC group) and in the treatment of relapsed/chemoresistant chronic lymphocytic leukemia (3% in the R-FC group).
IgG concentration
Maintenance therapy (non-Hodgkin's lymphoma) up to 2 years
After induction therapy, the IgG concentration was below the lower limit of normal (
Special categories of patients
Rituximab monotherapy (for 4 weeks)
Elderly age (>65 years): the frequency and severity of all adverse reactions and grade 3 and 4 adverse reactions does not differ from that in younger patients.
Combination therapy
Older age (65 years and older): In first-line therapy and in treatment of relapsed/chemoresistant chronic lymphocytic leukemia, the incidence of grade 3 and 4 side effects from the blood and lymphatic system was higher compared to younger patients.
High tumor load (diameter of single lesions more than 10 cm): increased frequency of grade 3 and 4 adverse reactions.
Repeated therapy: the frequency and severity of adverse reactions do not differ from those during initial therapy.
Information on the post-registration use of rituximab for non-Hodgkin's lymphoma and chronic lymphocytic leukemia
From the cardiovascular system: severe cardiovascular events associated with infusion reactions, such as heart failure and myocardial infarction, mainly in patients with a history of cardiovascular disease and/or receiving cytotoxic chemotherapy; very rarely - vasculitis, mainly cutaneous (leukocytoclastic).
From the respiratory system: respiratory failure and pulmonary infiltrates caused by infusion reactions; In addition to pulmonary adverse events due to infusion reactions, interstitial lung disease, in some cases fatal, has been observed.
From the circulatory and lymphatic system: reversible acute thrombocytopenia associated with infusion reactions.
From the skin and its appendages: rarely - severe bullous reactions, toxic epidermal necrolysis and Stevens-Johnson syndrome, in some cases with death.
From the nervous system: rarely - neuropathy of the cranial nerves in combination with peripheral neuropathy or without it (marked decrease in visual acuity, hearing, damage to other sensory organs, paresis of the facial nerve) during various periods of therapy up to several months after completion of the course of treatment with rituximab . Cases of posterior reversible encephalopathy (PRES)/posterior reversible leukoencephalopathy syndrome (PRLS) have been reported in patients treated with rituximab. Symptoms included blurred vision, headache, seizures and mental disturbances, with or without increased blood pressure. The diagnosis of PRES/PRLS can be confirmed using brain imaging techniques. In the cases described, patients had risk factors for developing PRES/PRLS, such as underlying disease, elevated blood pressure, immunosuppressive therapy and/or chemotherapy.
From the body as a whole, reactions at the injection site: rarely - serum sickness.
Infections: reactivation of hepatitis B virus (in most cases with a combination of rituximab and cytotoxic chemotherapy); as well as other severe viral infections (primary infection, viral reactivation or exacerbation), some of which were fatal, caused by cytomegalovirus, Varicella zoster, Herpes simplex, JC polyomavirus (PML), hepatitis C virus.
When rituximab was prescribed for indications not covered by the instructions for medical use, sarcoma progression was observed in patients with previously diagnosed Kaposi's sarcoma (most patients were HIV-positive).
From the gastrointestinal tract: perforation of the stomach and/or intestines (possibly fatal) when rituximab is combined with chemotherapy for non-Hodgkin's lymphoma.
From the blood and lymphatic system: rarely - neutropenia that occurred 4 weeks after the last administration of rituximab; a transient increase in IgM levels in patients with Waldenström's macroglobulinemia, followed by a return to its original value after 4 months.
Cases of overdose in humans have not been observed. Single doses of rituximab above 1000 mg have not been studied. The maximum dose of 5000 mg was prescribed to patients with chronic lymphocytic leukemia, no additional safety data were obtained. Due to the increased risk of infectious complications when the pool of B-lymphocytes is depleted, infusions should be canceled or reduced, and the need for a comprehensive general blood test should be considered.
