scholarly journals Radioimmunotherapy in Non-Hodgkin’s Lymphoma: Retrospective Adverse Event Profiling of Zevalin and Bexxar

2019 ◽  
Vol 12 (4) ◽  
pp. 141 ◽  
Author(s):  
Sachpekidis ◽  
Jackson ◽  
Soldatos
Keyword(s):  
Adverse Event ◽  
Monoclonal Antibodies ◽  
Hodgkin’S Lymphoma ◽  
Single Agent ◽  
Adverse Event Reporting System ◽  
Hodgkin's Lymphoma ◽  
World Health ◽  
Antibody Treatment ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

The development of monoclonal antibodies has dramatically changed the outcome of patients with non-Hodgkin’s lymphoma (NHL), the most common hematological malignancy. However, despite the satisfying results of monoclonal antibody treatment, only few NHL patients are permanently cured with single-agent therapies. In this context, radioimmunotherapy, the administration of radionuclides conjugated to monoclonal antibodies, is aimed to augment the single-agent efficacy of immunotherapy in order to deliver targeted radiation to tumors, particularly CD20+ B-cell lymphomas. Based on evidence from several trials in NHL, the radiolabeled antibodies 90Y-ibritumomab tiuxetan (Zevalin, Spectrum Pharmaceuticals) and 131I-tositumomab (Bexxar, GlaxoSmithKline) received FDA approval in 2002 and 2003, respectively. However, none of the two radioimmunotherapeutic agents has been broadly applied in clinical practice. The main reason for the under-utilization of radioimmunotherapy includes economic and logistic considerations. However, concerns about potential side effects have also been raised. Driven by these developments, we performed retrospective analysis of adverse events reporting Zevalin or Bexxar, extracted from the FDA’s Adverse Event Reporting System (FAERS) and the World Health Organization’s VigiBase repository. Our results indicate that the two radioimmunotherapeutic agents have both related and distinct side effect profiles and confirm their known toxicological considerations. Our work also suggests that computational analysis of real-world post-marketing data can provide informative clinical insights. While more prospective studies are necessary to fully characterize the efficacy and safety of radioimmunotherapy, we expect that it has not yet reached its full therapeutic potential in modern hematological oncology.

scholarly journals New monoclonal antibodies for non-Hodgkin's lymphoma

2008 ◽  
Vol 19 ◽  
pp. iv60-iv62 ◽  
Author(s):  
J.P. Leonard ◽  
P. Martin ◽  
J. Ruan ◽  
R. Elstrom ◽  
J. Barrientos ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

Immunotherapy for Non-Hodgkin's Lymphoma: Monoclonal Antibodies and Vaccines

2005 ◽  
Vol 23 (26) ◽  
pp. 6421-6428 ◽  
Author(s):  
David G. Maloney
Keyword(s):  
Monoclonal Antibodies ◽  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Patient Specific ◽  
Chimeric Antibody ◽  
Target Antigen ◽  
Host Immune System ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

Advances in the development of monoclonal antibodies have led to new agents rapidly incorporated into standard lymphoma therapy. The characteristics of the target antigen and the properties of the antibody including interaction with the host immune system have been found to correlate with outcome. Antibodies targeting the CD20 antigen on B cells have been most widely used, led by the chimeric antibody rituximab, now used in nearly all types of B-cell non-Hodgkin's lymphoma (NHL). New antibodies targeting CD20 with augmented complement or Fc receptor binding are now being evaluated and will eventually have to be compared with rituximab. Challenges to these new antibodies include the nearly universal use of rituximab early in NHL therapy, and its increasing use as maintenance therapy. It is not clear what the activity of these antibodies will be in rituximab-refractory patients. New antibodies targeting antigens such as CD40 and CD80 are also being tested alone and in combination with rituximab. Vaccine trials using patient-specific immunization with immunoglobulin idiotype (Ig-Id present on the surface of most B-cell NHL) isolated by molecular rescue or by cell hybridization techniques are also nearing completion. These approaches attempt to actively induce specific humoral or cellular immune responses to the Ig-Id by attaching the protein to a carrier protein and the use of an immunologic adjuvant such as granulocyte macrophage colony-stimulating factor. Prior rituximab appears to delay humoral responses to the idiotype but may still allow cellular responses. The incorporation of all these approaches into optimal NHL therapy remains a challenge.

Interim Analysis of a Phase II Study of Denileukin Diftitox (Ontak) for Relapsed/Refractory T-Cell Non-Hodgkin’s Lymphoma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2641-2641 ◽  
Author(s):  
Nam H. Dang ◽  
Barbara Pro ◽  
Fredrick B. Hagemeister ◽  
Dan Jones ◽  
Barry Samuels ◽  
...  
Keyword(s):  
T Cell ◽  
Tumor Cells ◽  
Phase Ii ◽  
Hodgkin’S Lymphoma ◽  
Phase Ii Study ◽  
Single Agent ◽  
Hodgkin's Lymphoma ◽  
Denileukin Diftitox ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

Abstract Denileukin diftitox (Ontak) is a fusion protein combining the enzymatically active domain of diphtheria toxin and the full-length sequence of interleukin-2 (IL-2) that targets tumor cells expressing the IL-2 receptor (IL-2R). The drug has established efficacy in cutaneous T-cell lymphoma (CTCL), and we have recently demonstrated its single-agent activity in B-cell non Hodgkin’s lymphoma (NHL) (Dang et al. Journal of Clinical Oncology. In Press). We initiated a phase II study to evaluate its efficacy in relapsed/refractory T-cell NHL, excluding CTCL. Denileukin diftitox was administered at a dose schedule of 18 μg/kg/day by IV infusion once daily for 5 days every three weeks, for up to 8 cycles. Premedications in the form of corticosteroids, antihistamines and fluids were given prior to each drug infusion to reduce the incidence and severity of acute hypersensitivity. 14 patients are currently evaluable for response. Median age was 57 (range 26–80), and mean number of previous treatments was 2.2 (range 1–4). Tumor CD25 status was determined by immunohistochemistry and/or flow cytometry, with CD25-positivity being defined as 10% or more of tumor cells expressing detectable CD25. Of the 7 patients with CD25+ T-NHL, there were 2 CR (1 case of Alk-1 negative ALCL and 1 case of PTCL), 3 PR (1 case of PTCL and 2 cases of angioimmunoblastic lymphoma), 1 SD (1 case of PTCL) and 1 PD (1 case of PTCL). Of the 7 patients with CD25− T-NHL, there were 2 PR (1 case of PTCL and 1 case of T/NK-lymphoma), 4 SD (3 cases of PTCL and 1 case of Sezary syndrome), and 1 PD (1 case of angioimmunoblastic lymphoma). Overall response rate (CR+ PR) was 50%, with 2 of 14 patients having CR (14%) and 5 of 14 patients having PR (36%). One patient with Alk-1negative ALCL still has an ongoing CR at 15+ months. Treatment was well-tolerated, with the majority of toxicity being grade 1 or 2 and transient. Denileukin diftitox appears to have activity in relapsed/refractory T-cell NHL, and is well-tolerated at the dosing schedule tested. Additional patients are being studied to further evaluate the relationship between detectable CD25 expression and tumor response to denileukin diftitox.

A Multicenter Phase II Trial of Etoposide, Methylprednisolone, High-Dose Cytarabine, and Oxaliplatin (ESHAOx) for Patients with Refractory/Relapsed Aggressive Non-Hodgkin’s Lymphoma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3446-3446
Author(s):  
Sun Jin Sym ◽  
Hye Jin Kang ◽  
Seung-Hyun Nam ◽  
Hoyoung Kim ◽  
Seok Jin Kim ◽  
...  
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Single Agent ◽  
Hodgkin's Lymphoma ◽  
High Dose ◽  
Hematologic Toxicity ◽  
Salvage Regimen ◽  
Hematopoietic Stem ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
High Dose Cytarabine

Abstract Etoposide (E), methylprednisolone (S), high-dose cytarabine (HA), and cisplatin (P) (ESHAP) combination is commonly used salvage regimen for non-Hodgkin’s lymphoma (NHL). Oxaliplatin (Ox), a new platinum derivative, showed substantially different cytotoxic activity and adverse effects from both cisplatin and carboplatin. In addition, single-agent oxaliplatin was reportedly active in patients with NHL. We conducted to investigate the efficacy and toxicity of ESHAOx combination, substituting oxaliplatin for cisplatin in ESHAP combination, for relapsed/refractory aggressive NHL patients. Main eligibility criteria included aggressive NHL and failure to achieve a complete remission or recurrent disease after previous chemotherapy. ESHAOx consisted of E, 40 mg/m2 on days 1 to 4; S, 500 mg on days 1 to 5; HA, 2 g/m2 on day 5; and Ox, 130 mg/m2 on day 1, every 3 weeks. Eligible patients were scheduled to receive a maximum of 6 cycles, and high dose chemotherapy and hematopoietic stem cell rescue allowed. Responses were evaluated every 3 cycles. All patients gave written informed consent before study entry. Between May 2006 and January 2007, 27 patients were enrolled. Nineteen (70%) patients with relapsed, 8 patients with refractory, and 10 (37%) patients with IPI 3–5 were included in this study. A total of 102 cycles were administered for a median number of 4 (range 1–6 cycles) per patient. There were 8 (30%) complete responses and 9 (33%) partial responses, producing an overall response rate of 63% (95% CI, 45–81%). Most common grade 3/4 toxicity of the courses was myelosuppression with including neutropenia (55%) and thrombocytopenia (33%). Non-hematologic toxicity was very favorable. No significant renal and neurotoxicity was demonstrated. There was one treatment-related death due to neutropenic sepsis. The results of ESHAOx combination showed highly antitumor activity and favorable toxicity profile, suggesting it can be used as salvage regimen for relapsed/refractory aggressive NHL patients.

scholarly journals Comparison of combined and single-agent chemotherapy in non-Hodgkin's lymphoma of favourable histological type.

BMJ ◽  
1978 ◽  
Vol 1 (6112) ◽  
pp. 533-537 ◽  
Author(s):  
T A Lister ◽  
M H Cullen ◽  
M E Beard ◽  
R L Brearley ◽  
J M Whitehouse ◽  
...  
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Single Agent ◽  
Histological Type ◽  
Hodgkin's Lymphoma ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Single Agent Chemotherapy

Novel and Engineered Anti–B-Cell Monoclonal Antibodies for Non-Hodgkin’s Lymphoma

2008 ◽  
Vol 45 (2) ◽  
pp. 126-132 ◽  
Author(s):  
Peter Martin ◽  
Richard R. Furman ◽  
Jia Ruan ◽  
Rebecca Elstrom ◽  
Jacqueline Barrientos ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

Primary non-Hodgkin's lymphoma of the CNS treated with BVAM or CHOD/BVAM chemotherapy before radiotherapy.

1996 ◽  
Vol 14 (3) ◽  
pp. 945-954 ◽  
Author(s):  
E M Bessell ◽  
F Graus ◽  
J A Punt ◽  
J L Firth ◽  
D T Hope ◽  
...  
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Whole Brain Radiotherapy ◽  
Hodgkin's Lymphoma ◽  
World Health ◽  
Poor Performance Status ◽  
Significant Treatment ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

PURPOSE To assess whether chemotherapy that includes drugs that cross the blood-brain barrier improves survival in primary CNS non-Hodgkin's lymphoma (PCNSL) when combined with radiotherapy. PATIENTS AND METHODS Thirty-four patients, with no evidence of human immunodeficiency virus type 1 (HIV-1) infection, were treated with the related chemotherapy regimens of carmustine (BCNU), vincristine, cytarabine, and methotrexate (BVAM; 12 patients), cyclophosphamide, doxorubicin, vincristine, and dexamethasone (CHOD)/BVAM (17 patients) and intensified CHOD/BVAM (five patients) between 1986 and 1994. The median age was 60 years (range, 16 to 73) and 47% had a performance status of 3 or 4 (Eastern Cooperative Oncology Group [ECOG]/World Health Organization [WHO]). Ten patients were treated with BVAM chemotherapy between 1986 and 1989, and subsequently 17 patients were treated with CHOD/BVAM (cytarabine 3 g/m2). Twenty of these 27 patients received whole-brain radiotherapy (craniospinal in four). RESULTS The complete response (CR) rate at the completion of chemotherapy was 63% for BVAM and 67% for CHOD/BVAM; more neutropenia occurred with CHOD/BVAM. The 5-year actuarial probability of survival of all 34 patients was 33% (95% confidence interval [CI], 14% to 52%), with so far only one recurrence after 2 years. Using multivariate analysis, age (P = .0005) and number of tumors at diagnosis (P = .0358) were prognostic factors. All five patients aged > or = 70 years died during or shortly after chemotherapy. Performance status was not an independent variable. CONCLUSION The BVAM or CHOD/BVAM regimens can be delivered despite neutropenia without significant treatment delay or dose reduction in patients less than 70 years of age. Further intensification of this type of chemotherapy is probably not possible with patients of this age, many of whom have a poor performance status.

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