Iodine-131 Tositumomab for Patients With Transformed, Low-Grade Non-Hodgkin’s Lymphoma: Overall Clinical Trial Experience

Publication
Article
OncologyONCOLOGY Vol 14 No 3
Volume 14
Issue 3

Transformation of low-grade non-Hodgkin’s lymphoma (NHL) to a more aggressive histology is associated with a very poor response to chemotherapy and shortened survival. Therefore, new therapeutic agents are needed. Tositumomab/iodine-

Transformation of low-grade non-Hodgkin’s lymphoma (NHL) to a more aggressive histology is associated with a very poor response to chemotherapy and shortened survival. Therefore, new therapeutic agents are needed. Tositumomab/iodine-131 tositumomab (Bexxar) is a new radioimmunotherapy in development for the treatment of relapsed or refractory, low-grade or transformed, low-grade NHL.

Data from 49 patients with transformed, low-grade NHL from four phase I-III studies were analyzed. The patients were initially diagnosed with low-grade (small cell lymphocytic; follicular small cleaved cell; or follicular mixed cell, with > 50% small cleaved cell). Transformation required biopsy demonstration of a more aggressive histology at any time prior to study entry, and included diffuse large cell (27 patients), follicular large cell (12 patients), diffuse mixed cell (10 patients), large cell immunoblastic (2 patients), and other higher-grade histologies (8 patients).

Patients had received a median of 4 (range, 1 to 11) prior chemotherapy regimens, and 29 (49%) of 59 patients had not responded to their last chemotherapy regimen. Median duration of response to the last chemotherapy regimen was 4.2 months (range, 2.0 to 16.0 months). Median age was 59 years; 33 patients were male; median time from diagnosis to study entry was 80 months; 32 (56%) patients had elevated lactate dehydrogenase (LDH); and 17 (29%) patients had a positive baseline bone marrow biopsy (< 25% lymphoma involvement).

Patients generally received a single dosimetric dose (450 mg of intravenous ([IV] of tositumomab, followed by 35 mg of tositumomab radiolabeled with 5 mCi of iodine-131. Patients then had three whole-body counts obtained over the next 7 days. The whole-body counts were used to calculate the required activity (mCi) to deliver the desired therapeutic dose (65 cGy for platelets 100,000 to 149,999 cells/mm³ and 75 cGy for platelets ³ 150,000 cells/mm³). A single therapeutic dose (450 mg of tositumomab IV, followed by 35 mg of tositumomab containing an appropriate activity [mCi] of iodine-131 to deliver the specified total -body dose [cGy]) was administered 7 to 14 days after the dosimetric dose.

An investigator-assessed response was observed in 26 (53%) of 49 patients following iodine-131 tositumomab, and 16 (33%) patients achieved a complete response (CR). Median duration of response was 12.7 months (95% confidence interval [CI], 6.9 to 36.5 months). Median duration of CR was 36.5 months (95% CI, 14.3 to 36.5 months).

The principal toxicity was hematologic; absolute neutrophil count (ANC) was < 500 cells/mm³ in 19% of patients, and platelets were < 10,000 cells/mm³ in 4%. The nadir typically occurred at week 5 to 6, with recovery by week 8 to 9.

Transient, mild to moderate nonhematologic toxicities occurred, with the most frequent events being fever, fatigue, and nausea. Five patients developed human antimurine antibodies.

Median survival from study entry was 21.9 months (95% CI, 14.1 months to not reached).

CONCLUSION: These results demonstrate that iodine-131 tositumomab is a safe and effective therapy for the treatment of patients with transformed, low-grade NHL.

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

Articles in this issue

Comparative Economic Analysis of the Treatment of Relapsed Low-Grade B-Cell Non-Hodgkin’s Lymphoma (NHL) in France Using CHOP, Fludarabine, or Rituximab
FHIT Gene, Smoking, and Cervical Cancer
Final Report on the Safety and Efficacy of Retreatment With Rituximab for Patients With Non-Hodgkins Lymphoma
Prospective, Randomized, Controlled Study of Zevalin Radioimmunotherapy Compared to Rituximab Immunotherapy for B-Cell, Non-Hodgkins Lymphoma: Interim Results
IOM Medical Error Estimates Questioned, But Legislation Considered
Less Toxic Therapies for Hodgkin’s Disease May Reduce Secondary Cancers
Preserving Fertility in Young Women With Ovarian Cancer Does Not Decrease Survival
Iodine-131 Tositumomab for Patients With Transformed, Low-Grade Non-Hodgkin’s Lymphoma: Overall Clinical Trial Experience
Survival Rates Significantly Worse For African-Americans With Endometrial Cancer
Rituximab Has Significant Activity in Patients With Chronic Lymphocytic Leukemia
Responders to Rituximab Show Continued Tumor Regression Over Time and a Progression-Free Survival That Correlates With Response Classification
PhRMA Criticizes FDA’s Proposed Rule on Antibiotic Approvals
Phase II Study of Rituximab in Combination With CHOP in Patients With Previously Untreated Intermediate- or High-Grade Non-Hodgkin’s Lymphoma
New Antibiotic Effective in Treating Gram-Positive Bacteremia
Reduced-Dose Zevalin Radioimmunotherapy for Relapsed or Refractory B-Cell Non-Hodgkin&#146;s Lymphoma Patients With Preexisting Thrombocytopenia: Report of Interim Results of a Phase II Trial
Related Videos
A panel of 4 experts on multiple myeloma
Data from the REVEAL study affirm elevated white blood cell counts and higher variant allele frequency as risk factors for progression in polycythemia vera.
Video 1 - 4 KOLs are featured in "Triaging and Prioritizing Patients with Multiple Myeloma"
Video 1 - 4 KOLs are featured in "CAR T-Cell Therapy: Leukapheresis Practices"
A panel of 4 experts on multiple myeloma
A panel of 4 experts on multiple myeloma
Additional analyses of patient-reported outcomes and MRD status in the QuANTUM-First trial are also ongoing, says Harry P. Erba, MD, PhD.
Overall survival data with blinatumomab in the phase 3 E1910 study may be an “important development” in CD19-positive B-ALL.
Intraoperative radiation therapy may allow surgical and radiation oncologists to collaboratively visualize at-risk areas in patients with cancer.
Positive margin rates have not appeared to improve for patients with cancer undergoing surgical care based on several prior studies.
Related Content