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.

Unique Toxicities and Resistance Mechanisms Associated with Monoclonal Antibody Therapy

Hematology ◽  
2005 ◽  
Vol 2005 (1) ◽  
pp. 329-334 ◽  
Author(s):  
Jonathan W. Friedberg
Keyword(s):  
Follicular Lymphoma ◽  
Single Agent ◽  
Antibody Therapy ◽  
Resistance Mechanisms ◽  
Complement Dependent Cytotoxicity ◽  
Dependent Cell ◽  
Impact On Treatment ◽  
Anti Cd20 ◽  
In Vivo Cytotoxicity

Abstract Anti-CD20 therapy has had a truly dramatic impact on treatment and outcome of patients with follicular lymphoma. Unfortunately, the majority of responses to single-agent rituximab are incomplete, and all patients with follicular lymphoma will experience disease progression at some point following rituximab therapy. Rituximab has multiple mechanisms of inducing in vivo cytotoxicity, including antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, direct apoptotic signaling, and possible vaccinal effects. The cellular microenvironment within follicular lymphoma has a profound impact on which mechanism is dominant, and confers resistance in many situations. Both tumor-associated and host-associated factors also contribute to rituximab resistance. There are multiple potential approaches to overcoming rituximab resistance, including rational biologic combination immunotherapy, engineered antibodies, and radioimmunoconjugates. Improved ability to overcome resistance will require further elucidation of critical signaling pathways involved in rituximab induced cytotoxicity and a comprehensive understanding of interactions between its multiple mechanisms of action.

scholarly journals Prospects in the management of patients with follicular lymphoma beyond first-line therapy

Haematologica ◽  
2022 ◽  
Vol 107 (1) ◽  
pp. 19-34 ◽  
Author(s):  
David Qualls ◽  
Gilles Salles
Keyword(s):  
Follicular Lymphoma ◽  
Kinase Inhibitors ◽  
Treatment Strategies ◽  
Cytotoxic Agents ◽  
Treatment Regimens ◽  
First Line Therapy ◽  
Phase Ii Studies ◽  
Clinical Scenarios ◽  
Histological Transformation ◽  
Anti Cd20

The management of patients with relapsed or refractory follicular lymphoma has evolved markedly in the last decade, with the availability of new classes of agents (phosphoinositide 3-kinase inhibitors, immunomodulators, epigenetic therapies, and chimeric antigen receptor T cells) supplementing the multiple approaches already available (cytotoxic agents, anti-CD20 antibodies, radiation therapy, radioimmunotherapy, and autologous and allogeneic transplants). The diversity of clinical scenarios, the flood of data derived from phase II studies, and the lack of randomized studies comparing treatment strategies preclude firm recommendations and require personalized decisions. Patients with early progression require specific attention given the risk of histological transformation and their lower response to standard therapies. In sequencing therapies, one must consider prior treatment regimens and the potential need for future lines of therapy. Careful evaluation of risks and expected benefits of available options, which vary depending on location and socioeconomics, should be undertaken, and should incorporate the patient’s goals. Preserving quality of life for these patients is essential, given the likelihood of years to decades of survival and the possibility of multiple lines of therapy. The current landscape is likely to continue evolving rapidly with other effective agents emerging (notably bispecific antibodies and other targeted therapies), and multiple combinations being evaluated. It is hoped that new treatments under development will achieve longer progression-free intervals and minimize toxicity. A better understanding of disease biology and the mechanisms of these different agents should provide further insights to select the optimal therapy at each stage of disease.

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 NOVEL DRUGS IN FOLLICULAR LYMPHOMA

2016 ◽  
Vol 8 ◽  
pp. 2016061 ◽  
Author(s):  
Giuseppe Rossi ◽  
Antonella Anastasia
Keyword(s):  
Follicular Lymphoma ◽  
Treatment Strategies ◽  
Cell Receptor ◽  
Phase Iii ◽  
Non Hodgkin Lymphoma ◽  
Free Treatment ◽  
Phase Iii Trials ◽  
New Treatment ◽  
Anti Cd20 ◽  
Key Steps

Follicular lymphoma(FL) is the most common indolent non-Hodgkin lymphoma and constitutes 15% to 30% of lymphoma diagnoses. The natural history of the disease is characterized by recurrent relapses and progressively shorter remissions with a median survival of 10yrs. The impossibility of a chieving a definite cure, have prompted investigations into the possible role of more effective and less toxic strategies with innovative therapeutic agents.  Recently Casulo et al demonstrated that approximately 20% of patients with FL actually relapse within 2 years after achieving remission with R-CHOP and have a poor prognosis. It is conceivable that this particularly chemoresistant population would benefit from specifically targeting the biologic and genetic factors that likely contribute to their poor prognosis.Evolving strategies for difficult to treat FL patients have recently considered  immunomodulatory agents, new monoclonal antibodies as well as drugs targeting selective intracellular pathways. The importance of targeting the microenvironment together with the malignant FL cell has been particularly underscored. We review the most promising approaches, such as the combination of anti-CD20 antibodies with immunomodulatory drugs (Lenalidomide), with mAbs directed against other surface antigens such as CD22 and CD23 (epratuzumab, lumiliximab), with immunomodulatory antibodies such as PD-1, or with inhibitors of key steps in the B-cell receptor pathway signaling such as PI3K inibithors(idelalisib, duvelisib). Another highly attractive approach is the application of the bi-specific T-cell engaging (BiTE) antibody blinatumomab which targets both CD19 and CD3 antigens. Moreover, we highlight the potential of these therapies,  taking into account their toxicity. Of course we must wait for Phase III trials results to confirm the benefit of these new treatment strategies toward a new era of chemotherapy-free treatment for follicular lymphoma.

scholarly journals Preclinical Evaluation of the HDAC Inhibitor Chidamide in Transformed Follicular Lymphoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Mengya Zhong ◽  
Jinshui Tan ◽  
Guangchao Pan ◽  
Yuelong Jiang ◽  
Hui Zhou ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Follicular Lymphoma ◽  
Single Agent ◽  
Hdac Inhibitors ◽  
Treatment Strategies ◽  
Annexin V ◽  
Gene Encoding ◽  
New Treatment ◽  
Transformed Follicular Lymphoma

The key factors leading to transformed follicular lymphoma (t-FL) include the aberrations of epigenetic modifiers as early and driving events, especially mutations in the gene encoding for histone acetyltransferase. Therefore, reversal of this phenomenon by histone deacetylase (HDAC) inhibitors is essential for the development of new treatment strategies in t-FL. Several t-FL cell lines were treated with various doses of chidamide and subjected to cell proliferation, apoptosis and cell cycle analyses with CCK-8 assay, Annexin V/PI assay and flow cytometry, respectively. Chidamide dose-dependently inhibited cell proliferation, caused G0/G1 cycle arrest and triggered apoptosis in t-FL cells. In addition, the effects of chidamide on tumor growth were evaluated in vivo in xenograft models. RNA-seq analysis revealed gene expression alterations involving the PI3K-AKT signaling pathway might account for the mechanism underlying the antitumor activity of chidamide as a single agent in t-FL. These findings provide a basis for further clinical exploration of chidamide as a promising treatment for FL.

Combination Biologic Therapy as Initial Treatment for Follicular Lymphoma: Initial Results From CALGB 50701 - a Phase II Trial of Extended Induction Epratuzumab (anti-CD22) and Rituximab (anti-CD20)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 427-427 ◽  
Author(s):  
Barbara Grant ◽  
John P. Leonard ◽  
Jeffrey L Johnson ◽  
Lale Kostakoglu ◽  
Eric Hsi ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Follicular Lymphoma ◽  
Phase Ii ◽  
Stable Disease ◽  
Phase Ii Trial ◽  
Single Agent ◽  
Good Tolerability ◽  
Grade 3 ◽  
Anti Cd20

Abstract Abstract 427 Rituximab is effective as single agent therapy in the treatment of follicular lymphoma (FL), and when combined with chemotherapy has extended remissions and survival. Epratuzumab (Immunomedics), a humanized anti-CD22 monoclonal antibody, also has single agent activity in FL, and in combination with rituximab led to durable complete responses in the treatment of patients (pts) with relapsed and refractory indolent NHL. To evaluate the hypothesis that combining a second biological agent with rituximab might improve efficacy with good tolerability, the CALGB treated 60 previously untreated pts with epratuzumab and rituximab in a multicenter phase II trial and we report here the preliminary response and toxicity findings. Rituximab was administered at 375 mg/m2 iv weekly for four weeks, then every 8 weeks for four additional doses for a total of 8 doses over 9 months. Epratuzumab, was given at 360 mg/m2 two days before the first rituximab dose to assess toxicity. From week 2 on, epratuzumab was given before the rituximab on the same day for a total of 8 doses over 9 months. Fifty-seven evaluable pts were enrolled between May 2008 and September 2009. FLIPI scores at study entry were 13 (22%) low; 28 (47.5%) intermediate; and 18 (30.5%) high. Fifty-three pts completed all therapy through month 9. One pt was taken off therapy due to progression after month 5. One pt died during induction from line sepsis. Two pts were taken off study due to adverse events, 1 during induction (grade 4 thrombosis and MI), 1 following month 5 (dyspnea, hypoxia and pulmonary NOS). All other toxicities were grade 3 or lower, including fatigue (grade 3 3%, grade 2 17%), nodal pain (grade 3 5%, grade 2 8%), and cytokine release and pruritis (grade 2, 5% each). To date, there have been 19 CRs (33.3%), 29 PRs (50.9%)(ORR 84.2%); 9 (15.8%) had stable disease. All 19 CR patients completed all treatment. The mean time to CR was 9 months. Two patients progressed after a period of stable disease, and 25 of the 29 patients who achieved PR remain in response. All 19 CRs also remain in remission at this point with a median follow-up of 0.82 years (range 0.52 to 2.0). FLIPI score was not predictive of response. The CR rate in low risk pts was 31%, 44% in intermediate risk and 18% in high risk pts. There was a trend toward higher CR rate among patients with FcgR2A His (n=10, CR 60%) and to a lower CR rate among those with FcgR2A Arg (n=14, CR 14.3%). Correlations with PET scan at week 3, with tissue biomarkers and to statin use are being analyzed. Rituximab and epratuzumab is an effective and very well tolerated regimen with an ORR of 84% in previously untreated patients with follicular lymphoma. Disclosures: Off Label Use: Use of Epratuzumab, a humanized antiCD22 monoclonal antibody in treatment of follicular lymphoma. Leonard:BiogenIDEC: Consultancy; Genentech: Consultancy; Immunomedics: Consultancy. Jones:Glaxo Smith-Kline: Consultancy; Abbott: Research Funding. Cheson:Genentech: Consultancy.

Current First-line and Salvage Treatment Strategies in Patients with Advanced-stage Follicular Lymphoma

2010 ◽  
Vol 06 (02) ◽  
pp. 58
Author(s):  
Frank Heinzelmann ◽  
Michael Bamberg ◽  
Martin Weinmann ◽  
◽  
◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Treatment Options ◽  
Single Agent ◽  
Treatment Strategies ◽  
Long Term Results ◽  
Haematopoietic Stem Cell ◽  
Advanced Stage ◽  
First Line ◽  
Effective Treatment Option ◽  
Asymptomatic Patients

In patients with advanced-stage follicular lymphoma (FL) there are many treatment options available. Besides watchful waiting in asymptomatic patients, current first-line treatment strategies include rituximab ± single-agent chemotherapy, chemoimmunotherapy and radioimmunotherapy. In case of relapse, the use of chemoimmunotherapy, radioimmunotherapy and autologous haematopoietic stem cell transplantation (HSCT) results in enhanced response rates, progression-free survival (PFS) and overall survival (OS) compared with chemotherapy alone. However, long-term results are marred by high relapse rates and the risk of secondary malignancies after autologous HSCT. To date, in patients with relapsed/chemoresistant disease, myeloablative/reduced intensity conditioning protocols in combination with allogeneic HSCT presumably constitute the only curative approach but are associated with high treatment-related mortality. Although advances in supportive care have resulted in improved outcomes, reliable strategies for adequate patient selection are mandatory. In the palliative setting, low-dose involved-field irradiation constitutes an effective treatment option in order to control local symptoms with potential long-lasting response.

Efficacy of ocaratuzumab (AME-133v) in relapsed follicular lymphoma patients refractory to prior rituximab.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8081-8081 ◽  
Author(s):  
Jennifer L. Wayne ◽  
Kristen N. Ganjoo ◽  
Brad L. Pohlman ◽  
Sven De Vos ◽  
Ian W. Flinn ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Binding Affinity ◽  
Overall Response Rate ◽  
Single Agent ◽  
Progression Free Survival ◽  
Fold Increase ◽  
Dose Escalation Study ◽  
Free Survival ◽  
Dependent Cell ◽  
Anti Cd20

8081 Background: Ocaratzumab, previously known as AME-133v, is a humanized next-generation anti-CD20 monoclonal antibody. It has been optimized with a 13 to 20-fold increase in binding affinity to CD20 and improved binding to the low-affinity (F/F and F/V) polymorphisms of FcγRIIIa (CD16), which are thought to predict lower response rates and shorter duration of responses to rituximab. Methods: In a phase I dose escalation study in relapsed follicular lymphoma (FL) patients, ocaratuzumab was well-tolerated at doses up to 375 mg/m2 (Forero-Torres et al. CCR 2012). In a follow-on phase II trial, 44 patients with relapsed FL following prior rituximab and the low-affinity FcγRIIIa polymorphism (F-carriers) received 375 mg/m2 of ocaratuzumab weekly for 4 doses. In this study, overall response rate (ORR) was 36% and median progression free survival (PFS) was 91 weeks (Ganjoo et al. Haematologica 2011). Results: Amongst the 56 patients receiving 100 and 375 mg/m2 of ocaratuzumab, 8 patients had a previous time to progression of ≤ 180 days following their last rituximab treatment. These patients had a median of 2 prior rituximab treatments, (range 1-6 treatments), and median PFS following last treatment of 159 days. Five of the 8 patients showed a longer PFS after ocaratuzumab administration, compared with last rituximab treatment. All 5 patients expressed the homozygous low-affinity genotype of FcγRIIIa (F/F). At the time of study closure, 3 of the patients were still in remission (indicated by * in the table). Conclusions: This retrospective analysis suggests that ocaratuzumab may be non-cross-resistant to rituximab in patients with the low-affinity FcγRIIIa polymorphism. Prolonged PFS in selected patients following ocaratuzumab suggests that the increased binding affinity to CD16 and improved antibody-dependent cell-mediated cytotoxicity (ADCC) of this antibody is clinically relevant. As a single agent, ocaratuzumab may provide prolonged clinical benefit in relapsed FL patients and a clinical trial comparing ocaratuzumab to rituximab is in preparation. [Table: see text]

Outcomes of tyrosine kinase inhibitors after immunotherapy in advanced hepatocellular carcinoma: A multi-center study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16181-e16181
Author(s):  
Thomas Yau ◽  
Joycelyn Jie Xin Lee ◽  
Jeffrey Sum Lung Wong ◽  
Vikki Tang ◽  
Jess Chan ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Single Agent ◽  
Objective Response ◽  
Tumour Response ◽  
Advanced Hepatocellular Carcinoma ◽  
Primary Resistance ◽  
Multi Centre Study

e16181 Background: Immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) are widely adopted in contemporary advanced HCC (aHCC) treatment algorithms. Nevertheless, the optimal strategy for treatment after ICI exposure is unknown. We evaluated the pattern of use, response, survival and safety of TKIs in aHCC patients who previously received ICIs. Methods: We performed an international, multi-centre study of aHCC patients who received TKIs after prior treatment with ICIs. Objective response rate (ORR), disease control rate (DCR), time-to-progression (TTP), overall survival (OS) and adverse events (AE) were assessed. Results: Between January 2015 and December 2020, one-hundred and forty-eight patients were included. The median age was 63 (range 29-84) and 78.4% were of Child-Pugh Grade A. 75.7% had hepatitis-B related HCC. 64.9% received TKI as single agent and 35.1% received TKI in combination with other agents. 75% who received TKI combinations had concomitant ICIs. 48.6% had prior TKIs. The median follow-up was 23.3 months. For single agent TKI patients, the ORR was 14.6%, DCR was 38.5%, median TTP was 3.9 months (95% C.I. 3.3-4.5) and median OS was 8.6 months (95% C.I. 5.8-11.4). For patients receiving TKI combinations, the ORR was 25%, DCR was 38.5%, median TTP was 3.5 months (95% C.I. 1.7-5.2) and median OS was 15.1 months (95% C.I. 5.7-24.5). There were no significant differences in ORR, DCR and median OS between patients who had primary resistance to prior ICI compared to those with acquired ICI resistance and between those who were TKI-naive compared to those who were TKI-exposed. Notably, patients who received TKI-ICI combinations had significantly superior survival compared to single agent TKI patients (median OS 15.1 months (95% C.I. 6.7-23.5) vs. 8.6 months (95% C.I. 5.6-11.7), p = 0.011) but not significantly superior ORR, DCR or TTP. Amongst patients who received single agent TKI and were naive to both sorafenib and lenvatinib, those who received lenvatinib had significantly superior DCR, TTP and OS compared to those who received sorafenib (DCR 51.5% vs 25.8%, p = 0.035; median TTP 6.3 months (95% C.I. 3.0-9.7) vs. 1.8 months (95% C.I. 0-3.6), p = 0.003; median OS 12.0 months (95% C.I. 7.0-17.0) vs. 5.9 months (95% C.I. 1.9-10.0), p = 0.008). 70.3% and 15.5% of all patients, and 77.1% and 15.6% of patients who received single agent TKI experienced all grade and grade ≥3 AEs respectively. The most common AEs were hand foot syndrome, skin rash and diarrhea. Conclusions: TKIs can achieve encouraging anti-tumour response and survival outcomes with acceptable safety in prior ICI-treated aHCC patients. Moreover, TKI-ICI combinations were associated with better survival than single agent TKIs. Notably, among patients who received single agent TKIs, lenvatinib had significantly better responses and survival results than sorafenib.

Evidence for Fcγ Receptor IIIA-Independent Rituximab Effector Mechanisms in Patients with Follicular Lymphoma Treated with Combined Immuno-Chemotherapy.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 590-590 ◽  
Author(s):  
Sebastian Boettcher ◽  
Christiane Pott ◽  
Matthias Ritgen ◽  
Wolfgang Hiddemann ◽  
Michael Unterhalt ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Single Agent ◽  
Observation Time ◽  
Taqman Assay ◽  
High Dose ◽  
Low Grade ◽  
Fcγ Receptor ◽  
Large Patient ◽  
Lymphoma Study Group ◽  
Anti Cd20

Abstract The response to the anti-CD20 antibody Rituximab used as a single agent in follicular lymphoma (FL) patients can be predicted by the valine/phenylalanine (V/F) dimorphism of amino acid 158 of Fcγ Receptor IIIA (Fcγ RIIIA) (Cartron et al., Blood99: 754, 2002; Weng and Levy, JCO21: 3940, 2003). This suggested important contributions for Fcγ RIIIA mediated mechanisms like antibody dependent cellular cytotoxicity to the efficacy of the antibody. Recently, the German Low Grade Lymphoma Study Group (GLSG) demonstrated a significant shorter time to treatment failure (TTF) in patients who received standard CHOP (cyclophosphamide d1, doxorubicin d1, vincristin d1, prednisone d1-5) chemotherapy only compared to patients who received Rituximab (d1) plus CHOP (R-CHOP). Estimated median TTF was 2.6 years in FL patients treated with CHOP and was not reached after 3 years observation time in R-CHOP treated FL patients (p<0.0007) (Blood 102, Abstract # 352, 2003). We examined the Fcγ RIIIA dimorphism in 75 FL patients from this GLSG trial who were treated with 6 to 8 cycles R-CHOP followed by interferon maintenance or high dose chemo-radiotherapy and autologous stem cell transplantation. Using a TaqMan assay with allele specific fluorochrome labelled probes we detected a V/V genotype in 8 patients (10.7%), a V/F genotype in 38 patients (50.6%), and an F/F genotype in 29 patients (38.7%). Patients with different Fcγ RIIIA status responded similarly to R-CHOP (CR rate: V/V 37.5%, V/F 36.8%, F/F 24.1%; overall response rate: V/V 100.0 %, V/F 97.4%, F/F 96.6%; ns). Moreover, TTF was not significantly different between the groups with V/V, V/F, and F/F Fcγ RIIIA(log rank p = 0.48) after a median observation time of 24 months. A correlation between the Fcγ RIIIA status and the efficacy of R-CHOP could not be demonstrated in this large patient cohort. On the other hand it is evident that R-CHOP treated patients significantly benefited from the addition of Rituximab to CHOP chemotherapy in comparison to the standard arm of this randomized trial. This observation supports the hypothesis that the anti-lymphoma effects of Rituximab when used in combination with chemotherapy might be mediated by Fcγ RIIIA-independent mechanisms such as complement dependent cytotoxicity or direct apoptosis induction.

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