scholarly journals A re-examination of radioimmunotherapy in the treatment of non-Hodgkin lymphoma: prospects for dual-targeted antibody/radioantibody therapy

Blood ◽  
2009 ◽  
Vol 113 (17) ◽  
pp. 3891-3895 ◽  
Author(s):  
Robert M. Sharkey ◽  
Oliver W. Press ◽  
David M. Goldenberg
Keyword(s):  
Hodgkin Lymphoma ◽  
New Technologies ◽  
Single Agent ◽  
Objective Response ◽  
Antibody Therapy ◽  
Careful Consideration ◽  
Igg Antibody ◽  
Non Hodgkin Lymphoma ◽  
Cd20 Antibody ◽  
Anti Cd20

Abstract Antibody-based therapies, both unconjugated antibodies and radioimmunotherapy, have had a significant impact on the treatment of non-Hodgkin lymphoma. Single-agent rituximab is an effective therapy, but it is being increasingly used with combination chemotherapy to improve the objective response and its duration. The approved anti-CD20 radioimmunoconjugates (90Y-ibritumomab tiuxetan or 131I-tositumomab) have had encouraging results, with trials now seeking to incorporate a radioimmunoconjugate in various settings. However, new preclinical data raise important questions concerning current radioimmunoconjugate treatment regimens and ways to improve them. In radioconjugate therapy, nearly 900 mg of the unlabeled anti-CD20 IgG antibody is predosed to the patient before the anti-CD20 antibody conjugated to either 90Y or 131I is given. Combining an unconjugated anti-CD20 antibody therapy with a radioimmunoconjugate binding to a noncompeting antigen might improve responses by allowing optimal uptake of each agent. Preclinical models have indicated that careful consideration should be given to predosing when using competing antibodies, but that consolidation anti-CD20 therapy enhances the efficacy of radioimmunoconjugate therapy. New technologies, such as pretargeted radioimmunotherapy, also hold promise by reducing toxicity without sacrificing efficacy, and consideration should be given to fractionating or giving multiple radioimmunoconjugate treatments. This perspective discusses how these issues could affect current and future clinical trials.

scholarly journals Impaired Humoral Immunity to SARS-CoV-2 Vaccination in Non-Hodgkin Lymphoma and CLL Patients

2021 ◽  
Author(s):  
Catherine Diefenbach ◽  
Jessica Caro ◽  
Akiko Koide ◽  
Michael Grossbard ◽  
Judith Goldberg ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Neutralizing Antibodies ◽  
Close Contact ◽  
Humoral Response ◽  
Hematologic Malignancies ◽  
Igg Antibody ◽  
Neutralization Capacity ◽  
Non Hodgkin Lymphoma ◽  
Current Guidance ◽  
Anti Cd20

Patients with hematologic malignancies are a high priority for SARS-CoV-2 vaccination, yet the benefit they will derive is uncertain. We investigated the humoral response to vaccination in 53 non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), or CLL patients. Peripheral blood was obtained 2 weeks after first vaccination and 6 weeks after second vaccination for antibody profiling using the multiplex bead-binding assay. Serum IgG, IgA, and IgM antibody levels to the spike specific receptor binding domain (RBD) were evaluated as a measure of response. Subsequently, antibody-positive serum were assayed for neutralization capacity against authentic SARS-CoV-2. Histology was 68% lymphoma and 32% CLL; groups were: patients receiving anti- CD20-based therapy (45%), monitored with disease (28%), receiving BTK inhibitors (19%), or chemotherapy (all HL) (8%). SARS-CoV-2 specific RBD IgG antibody response was decreased across all NHL and CLL groups: 25%, 73%, and 40%, respectively. Antibody IgG titers were significantly reduced (p < 0.001) for CD20 treated and targeted therapy patients, and (p = 0.003) for monitored patients. In 94% of patients evaluated after first and second vaccination, antibody titers did not significantly boost after second vaccination. Only 13% of CD20 treated and 13% of monitored patients generated neutralizing antibodies to SARS-CoV-2 with ICD50s 135 to 1767, and 445 and > 10240. This data has profound implications given the current guidance relaxing masking restrictions and for timing of vaccinations. Unless immunity is confirmed with laboratory testing, these patients should continue to mask, socially distance, and to avoid close contact with non-vaccinated individuals.

Phase II Study of Ofatumumab in Relapsed Nodular Lymphocyte-Predominant Hodgkin Lymphoma: A Report from the German Hodgkin Study Group

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2729-2729
Author(s):  
Dennis A. Eichenauer ◽  
Helen Goergen ◽  
Annette Pluetschow ◽  
Karolin Behringer ◽  
Stefanie Kreissl ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Phase Ii ◽  
Research Funding ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Antibody Treatment ◽  
Non Hodgkin Lymphoma ◽  
Cd20 Antibody ◽  
Anti Cd20

Abstract Background: Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) accounts for approximately 5% of all Hodgkin lymphoma (HL) cases. One hallmark of NLPHL is the consistent expression of CD20 on the malignant lymphocyte predominant (LP) cells. To shed more light on the role of anti-CD20 antibody treatment in relapsed NLPHL, we conducted a phase II study evaluating the fully humanized anti-CD20 antibody ofatumumab in 28 patients. Treatment consisted of 8 weekly doses (week 1: 300 mg, week 2-8: 1000 mg) of the antibody. Results: The median age of study patients was 45 years (range: 22-68) and the majority were male (64%). A median of 1 line of therapy (range: 1-5) had been applied prior to study treatment and 7/28 patients (25%) already had rituximab-containing treatment. At the final restaging 3 months after the end of treatment, response was documented in 27/28 patients (96%; 95%-CI: 84%-100%). After a median follow-up of 26 months, 1-year and 2-year progression-free survival (PFS) estimates were 93% and 80%, respectively. No patient died. Transformation into aggressive non-Hodgkin lymphoma (NHL) occurred in 2/28 patients (7.1%). No grade III/IV toxic events were observed. Conclusion: In summary, the anti-CD20 antibody ofatumumab represents a highly active and well tolerated treatment option in relapsed NLPHL. Longer follow-up is required for final conclusions. Disclosures Off Label Use: Ofatumumab in lymphocyte-predominant Hodgkin lymphoma. von Tresckow:Takeda: Consultancy; Celgene: Other: honoraria for preparation of scientific educational events; Novartis: Consultancy, Other: Travel and accomodation, Research Funding; Amgen: Other: honoraria for preparation of scientific educational events. Borchmann:Millennium: Research Funding. Engert:Takeda: Consultancy, Research Funding.

scholarly journals Pretargeted Versus Directly Targeted Radioimmunotherapy Combined with Anti-CD20 Antibody Consolidation Therapy of Non-Hodgkin Lymphoma

2009 ◽  
Vol 50 (3) ◽  
pp. 444-453 ◽  
Author(s):  
R. M. Sharkey ◽  
H. Karacay ◽  
C. R. Johnson ◽  
S. Litwin ◽  
E. A. Rossi ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Consolidation Therapy ◽  
Non Hodgkin Lymphoma ◽  
Cd20 Antibody ◽  
Anti Cd20

scholarly journals Safety and Clinical Activity of a Combination Therapy Comprising Two Antibody-Based Targeting Agents for the Treatment of Non-Hodgkin Lymphoma: Results of a Phase I/II Study Evaluating the Immunoconjugate Inotuzumab Ozogamicin With Rituximab

2013 ◽  
Vol 31 (5) ◽  
pp. 573-583 ◽  
Author(s):  
Luis Fayad ◽  
Fritz Offner ◽  
Mitchell R. Smith ◽  
Gregor Verhoef ◽  
Peter Johnson ◽  
...  
Keyword(s):  
Phase I ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Single Agent ◽  
Objective Response ◽  
B Cell Lymphoma ◽  
Response Rates ◽  
Low Grade ◽  
Inotuzumab Ozogamicin ◽  
Non Hodgkin Lymphoma

Purpose Inotuzumab ozogamicin (INO) is an antibody-targeted chemotherapy agent composed of a humanized anti-CD22 antibody conjugated to calicheamicin, a potent cytotoxic agent. We performed a phase I/II study to determine the maximum-tolerated dose (MTD), safety, efficacy, and pharmacokinetics of INO plus rituximab (R-INO) for treatment of relapsed/refractory CD20+/CD22+ B-cell non-Hodgkin lymphoma (NHL). Patients and Methods A dose-escalation phase to determine the MTD of R-INO was followed by an expanded cohort to further evaluate the efficacy and safety at the MTD. Patients with relapsed follicular lymphoma (FL), relapsed diffuse large B-cell lymphoma (DLBCL), or refractory aggressive NHL received R-INO every 4 weeks for up to eight cycles. Results In all, 118 patients received one or more cycles of R-INO (median, four cycles). Most common grade 3 to 4 adverse events were thrombocytopenia (31%) and neutropenia (22%). Common low-grade toxicities included hyperbilirubinemia (25%) and increased AST (36%). The MTD of INO in combination with rituximab (375 mg/m2) was confirmed to be the same as that for single-agent INO (1.8 mg/m2). Treatment at the MTD yielded objective response rates of 87%, 74%, and 20% for relapsed FL (n = 39), relapsed DLBCL (n = 42), and refractory aggressive NHL (n = 30), respectively. The 2-year progression-free survival (PFS) rate was 68% (median, not reached) for FL and 42% (median, 17.1 months) for relapsed DLBCL. Conclusion R-INO demonstrated high response rates and long PFS in patients with relapsed FL or DLBCL. This and the manageable toxicity profile suggest that R-INO may be a promising option for CD20+/CD22+ B-cell NHL.

scholarly journals Novel immunotherapy approaches to follicular lymphoma

Hematology ◽  
2018 ◽  
Vol 2018 (1) ◽  
pp. 194-199 ◽  
Author(s):  
Christopher R. Flowers ◽  
John P. Leonard ◽  
Loretta J. Nastoupil
Keyword(s):  
Follicular Lymphoma ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Single Agent ◽  
Antibody Therapy ◽  
Treatment Strategies ◽  
Careful Consideration ◽  
Optimal Timing ◽  
Phosphatidylinositol 3 Kinase ◽  
Anti Cd20

AbstractFollicular lymphoma (FL) remains a lymphoma subtype that is remarkably sensitive to immunotherapy-based treatment strategies. Anti-CD20 antibody therapy administered as a single agent and in combination as a first-line treatment and at relapse continues to be the most broadly used therapy for this disease. Autologous and allogeneic stem cell transplantation provide meaningful durable remissions for patients with FL. However, identifying the most suitable patients and the optimal timing for these approaches has become increasingly challenging with the advent of novel therapies. Lenalidomide and phosphatidylinositol 3-kinase inhibitors are emerging as agents that can be applied in the relapsed setting. Other immunotherapy approaches, including checkpoint inhibitors and chimeric antigen receptor T cells, appear promising but remain experimental. Utilization of all forms of immunotherapy requires careful consideration of the unique toxicities associated with these agents and the means to mitigate them by selection of appropriate patients, optimal timing, and the use of supportive care.

Therapeutic and palliative benefit from single-agent irinotecan in multiply treated and highly refractory cases of lymphoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19554-e19554
Author(s):  
D. D. Caces ◽  
J. Halaas ◽  
P. Hamlin ◽  
A. Noy ◽  
T. Kewalramani ◽  
...  
Keyword(s):  
Adverse Events ◽  
Hodgkin Lymphoma ◽  
Adverse Reactions ◽  
Cell Lymphoma ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Bulky Disease ◽  
Non Hodgkin Lymphoma ◽  
Refractory Lymphoma

e19554 Background: Multiple reports corroborate a role for irinotecan in the treatment of lymphoma. This study describes the Memorial Sloan Kettering experience with single-agent irinotecan in the management of heavily pretreated and highly refractory cases of lymphoma. Methods: Adult patients with histologically diagnosed relapsed or refractory lymphoma treated with irinotecan between 1/2001 and 8/2008 were identified. Treatment responses were evaluated based on the Revised Response Criteria for Malignant Lymphoma. Adverse reactions were evaluated based on the NCI Common Terminology Criteria for Adverse Events. Results: 30 patients were identified, 27 (90%) of whom received irinotecan after 3 or more prior regimens. 4 patients had Hodgkin Lymphoma (HL) and 26 had Non-Hodgkin lymphoma (NHL): 17 DLBCL, 6 transformed follicular lymphoma, 1 mantle cell lymphoma, 1 T-cell lymphoma and 1 Burkitt's. 25 patients were evaluable for response. 5 achieved an objective response (overall response rate 20%); 2 achieved complete remission (CR) and 3 partial remissions (PR). 8 patients (32%) had stable disease and 12 (48%) progressed on treatment. The median duration of response was 2.8 months (2.6–3.2), the median progression-free survival was 1.3 months (0.36 to 7.67) and the median overall survival was 3.9 months (0.30–63.4). Of the total cohort, 11 (36.6%) attained a clinically demonstrable improvement in symptomatology; 3 had resolution of pain syndromes, 5 had a reduction in the size or quantity of palpable masses, 2 had diminished fluid retention and 1 had an overall improvement in functional status. Adverse events occurring in more than 20% of cases included diarrhea (80%), leukopenia (67%), fatigue (36.6%) and thrombocytopenia (26.7%). Less common reactions included fever, febrile neutropenia, neuropathy, nausea and vomiting. Conclusions: Irinotecan has utility even in multiply treated and highly refractory cases of lymphoma. It can mitigate symptoms resulting from bulky disease and shows potential as a palliative treatment option. Although ORR was only 20%, two CRs were achieved suggesting benefit in select patients. Strategies that limit adverse reactions may enhance the agent's effectiveness in refractory lymphoma. No significant financial relationships to disclose.

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