Rituximab Therapy in Hematologic Malignancy Patients With Circulating Blood Tumor Cells: Association With Increased Infusion-Related Side Effects and Rapid Tumor Lysis

Publication
Article
OncologyONCOLOGY Vol 13 No 3
Volume 13
Issue 3

Rituximab (Rituxan) was recently approved for use in relapsed and previously treated low-grade non-Hodgkin’s lymphoma (NHL); however, little data exist regarding the safety of this agent in patients with hematologic malignancies who have a high number of tumor cells in the blood. We describe our preliminary experience with two such patients in whom we noted a rapid reduction of blood tumor cells, which was associated with severe pulmonary infusion-related toxicity and thrombocytopenia. Two additional patients were collected from physician-submitted reports of adverse events related to rituximab treatment.

Rituximab (Rituxan) was recently approved for use in relapsed and previously treated low-grade non-Hodgkin’s lymphoma (NHL); however, little data exist regarding the safety of this agent in patients with hematologic malignancies who have a high number of tumor cells in the blood. We describe our preliminary experience with two such patients in whom we noted a rapid reduction of blood tumor cells, which was associated with severe pulmonary infusion-related toxicity and thrombocytopenia. Two additional patients were collected from physician-submitted reports of adverse events related to rituximab treatment.

Pretreatment characterization of these patients included a median age of 60 years (range, 26-73 years) with the diagnosis of B-prolymphocytic leukemia (B-PLL; N = 2), chronic lymphocytic leukemia (CLL; N = 1), or transformed non-Hodgkin’s lymphoma (NHL; N = 1). All of these patients had elevated leukocyte counts as a consequence of blood tumor involvement, bulky adenopathy, and organomegaly.

All four patients developed a unique syndrome of severe infusion-related reactions characterized by fever (N = 4), rigors (N = 4), and bronchospasm with associated hypoxemia (N = 3), requiring temporary cessation of rituximab therapy. Concurrent with these symptoms was a rapid decrement in circulating tumor cell load (mean pretreatment tumor cell load, 98 × 109/L [range, 73-132 × 109/L] vs mean posttreatment tumor cell load, 11 × 109/L [range, 3.7-24.6 × 109/L]) with mild laboratory evidence of rapid tumor lysis. Thrombocytopenia, a finding not commonly associated with rituximab therapy, was noted in all four patients (mean pretreatment platelet count, 145 × 109/L; [range, 57-277 × 109/L] vs mean posttreatment platelet count, 56 × 109/L [range, 2-120 × 109/L]), requiring transfusion in one case.

Symptoms of this syndrome required hospitalization but resolved with supportive care. Subsequent rituximab treatments were well tolerated in all patients. Two subsequent patients with CLL and high blood tumor counts have been treated at our institution utilizing stepped-up dosing (100 mg on day 1 followed by completion of the remaining therapy on day 2) with demonstrated efficacy and thrombocytopenia but minimal infusion-related toxicity.

CONCLUSION: Rituximab administration in patients with hematologic malignancies who have blood tumor cell involvement may be associated with a higher frequency of severe initial infusion-related reactions and thrombocytopenia, mandating careful clinical monitoring. Given the preliminary activity of rituximab in these patients, future studies in CLL and PLL possibly utilizing a stepped-up dosing schedule appear warranted.

Click here for Dr. Bruce Cheson’s commentary on this abstract.

Articles in this issue

WHO Declares Lymphatic Mapping to Be the Standard of Care for Melanoma
Rituximab: Phase II Retreatment Study in Patients With Low-Grade or Follicular Non-Hodgkin’s Lymphoma
Response Criteria for NHL: Importance of “Normal” Lymph Node Size and Correlations With Response
Chemotherapy Plus Radiation Improves Survival in Patients With Cervical Cancer
A Randomized Trial of Fludarabine, Mitoxantrone (FM) Versus Doxorubicin, Cyclophosphamide, Vindesine, Prednisone (CHEP) as First Line Treatment in Patients With Advanced Low-Grade Non-Hodgkin's Lymphoma: A Multicenter Study by GOELAMS Group
Navelbine Increased Elderly Lung Cancer Patients’ Survival
Fludarabine Versus Conventional CVP Chemotherapy in Newly C Diagnosed Patients With Stages III and IV Low-Grade Malignant Non-Hodgkin’s Lymphoma: Preliminary Results From a Prospective, Randomized Phase III Clinical Trial in 381 Patients
Multicenter, Phase III Study of Iodine-131 Tositumomab (Anti-B1 Antibody) for Chemotherapy-Refractory Low-Grade or Transformed Low-Grade Non-Hodgkin’s Lymphoma
T-Cell–Depleted Allogeneic Bone Marrow Transplant From HLA-Matched Sibling Donors for Non-Hodgkin’s Lymphoma
Consensus Statement on Prevention and Early Diagnosis of Lung Cancer
In Vivo Purging and Adjuvant Immunotherapy With Rituximab During PBSC Transplant For NHL
Fludarabine and Cyclophosphamide: A Highly Active and Well-Tolerated Regimen for Patients With Previously Untreated Indolent Lymphomas
Campath-1H Monoclonal Antibody in Therapy for Advanced Low-Grade Non-Hodgkin’s Lymphomas: A Phase II Study
AIDS Drugs Effective Against Most Common HIV Strain
Rituximab Therapy in Previously Treated Waldenström’s Macroglobulinemia: Preliminary Evidence of Activity
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