The role of obinutuzumab in the management of follicular lymphoma

2019 ◽  
Vol 15 (31) ◽  
pp. 3565-3578 ◽  
Author(s):  
Jenny O’Nions ◽  
William Townsend
Keyword(s):  
Clinical Trials ◽  
Follicular Lymphoma ◽  
Progression Free Survival ◽  
Free Survival ◽  
Cd20 Antibody ◽  
Anti Cd20 ◽  
Almost All ◽  
Cd20 Antibodies

The outcomes for follicular lymphoma (FL) have improved significantly in recent years. This has been driven by an improved understanding of the pathobiology of FL and the development of therapeutic anti-CD20 antibodies. Combining rituximab with chemotherapy, coupled with its use as maintenance therapy, has contributed to significant improvements in disease control and progression-free survival. However, FL remains incurable and almost all patients invariably relapse. Therefore, there remains a need to develop novel therapeutic options and optimize existing regimens. Obinutuzumab (a first-in-class, glycoengineered, humanized type 2 anti-CD20 antibody) has been evaluated in a number of clinical trials. In this review, we will summarize the evaluable results of clinical trials investigating the efficacy of obinutuzumab in the treatment of FL.

scholarly journals Is there a role for anti-CD20 antibodies in CLL?

Hematology ◽  
2021 ◽  
Vol 2021 (1) ◽  
pp. 68-75
Author(s):  
Harsh R. Shah ◽  
Deborah M. Stephens
Keyword(s):  
Clinical Trials ◽  
Kinase Inhibitors ◽  
Residual Disease ◽  
Progression Free Survival ◽  
Antagonistic Effect ◽  
Lymphocytic Leukemia ◽  
Treatment Naïve ◽  
Anti Cd20 ◽  
Cd20 Antibodies

Abstract Anti-CD20 monoclonal antibodies (mAbs) have revolutionized the treatment of chronic lymphocytic leukemia (CLL) by improving survival of patients with CLL in conjunction with chemotherapy. However, the novel targeted agents such as Bruton tyrosine kinase inhibitors (BTKis) and venetoclax have now mostly replaced chemotherapy in frontline treatment of CLL. Several clinical trials have been conducted to examine the role of anti-CD20 mAbs in combination with BTK inhibitors and venetoclax. Addition of rituximab to ibrutinib does not improve progression-free survival (PFS) of treatment-naive patients with CLL, possibly related to ibrutinib's antagonistic effect on anti-CD20 antibodies. Alternatively, addition of a glycoengineered anti-CD20 mAb obinutuzumab to a more selective BTKi acalabrutinib may improve PFS but does not improve overall survival of patients with CLL in the frontline setting, pending long-term follow-up. Thus, we suggest that the addition of an anti-CD20 mAb to a BTKi is of most benefit to patients with autoimmune cytopenia or rapidly progressive disease. In contrast to BTKis, combination of fixed-duration venetoclax and anti-CD20 mAb can induce deep remission with high rates of undetectable minimal residual disease, correlating with improved survival of patients with CLL in both frontline and relapsed/refractory settings. In this review, we discuss clinical trials of BTKis and venetoclax that have investigated the role of anti-CD20 mAbs in frontline and relapsed settings of CLL treatment. We also provide an algorithm suggesting how anti-CD20 mAbs may be incorporated in the treatment of patients with CLL, including specific scenarios.

Clinical outcome of patients with follicular lymphoma receiving chemoimmunotherapy in the PRIMA study is not affected by FCGR3A and FCGR2A polymorphisms

Blood ◽  
2012 ◽  
Vol 120 (13) ◽  
pp. 2650-2657 ◽  
Author(s):  
Hervé Ghesquières ◽  
Guillaume Cartron ◽  
John Francis Seymour ◽  
Marie-Hélène Delfau-Larue ◽  
Fritz Offner ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Follicular Lymphoma ◽  
Response Rate ◽  
Single Agent ◽  
Progression Free Survival ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Free Survival ◽  
Rituximab Maintenance

Abstract In patients with follicular lymphoma treated with single-agent rituximab, single nucleotide polymorphisms in the FCGR3A gene are known to influence response and progression-free survival. The prognostic role of FCGR3A and FCGR2A polymorphisms in patients with follicular lymphoma treated with rituximab and chemotherapy combination remains controversial and has not been evaluated in the context of rituximab maintenance. FCGR3A and FCGR2A single nucleotide polymorphisms were evaluated in, respectively, 460 and 455 patients treated in the PRIMA study to investigate whether these were associated with response rate and patient outcome after rituximab chemotherapy induction and 2-year rituximab maintenance. In this representative patient cohort, complete and unconfirmed complete responses after rituximab chemotherapy were observed in 65%, 67%, 66% (P = .86) and 60%, 72%, 66% (P = .21) of FCGR3A VV, VF, FF and FCGR2A HH, HR, RR carriers, respectively. After 2 years of rituximab maintenance (or observation), response rates did not differ among the different genotypes. Progression-free survival measured from either treatment initiation or randomization to observation or maintenance was not influenced by these polymorphisms. These data indicate that FCGR3A and FCGR2A polymorphisms do not influence response rate and outcome when rituximab is combined with chemotherapy or used as maintenance treatment. The PRIMA study is registered at www.clinicaltrials.gov as NCT00140582.

scholarly journals Where does transplant fit in the age of targeted therapies?

Hematology ◽  
2019 ◽  
Vol 2019 (1) ◽  
pp. 287-293 ◽  
Author(s):  
Victor A. Chow ◽  
Ajay K. Gopal
Keyword(s):  
Follicular Lymphoma ◽  
Hematopoietic Cell Transplantation ◽  
Treatment Options ◽  
Progression Free Survival ◽  
Free Survival ◽  
Non Hodgkin Lymphoma ◽  
Low Toxicity ◽  
First Recurrence ◽  
Autologous Hct

Abstract The role of hematopoietic cell transplantation (HCT) for indolent lymphoma has evolved over the last 5 years with the availability of novel low-toxicity therapies and a better understanding of the prognosis of these entities. However, despite numerous treatment options for patients with follicular lymphoma, none are thought to be curative, and many require ongoing therapy with chronic toxicity. Historical trials indicate that autologous HCT as initial consolidation leads to improved progression-free survival, but not overall survival (OS) and, thus, is not typically recommended. However, autologous HCT for chemosensitive relapse can be carried out with ∼1% early mortality risk, affording disease control lasting a median of 3 to 5 years and the potential to improve OS. These results may compare favorably in efficacy, toxicity, and cost vs multiple sequential novel therapies with shorter durations of benefit. Recent data indicate that autologous HCT in follicular lymphoma patients with early initial progression will result in more than one third being alive and without relapse at 5 years, leading to improved OS when used within a year of the first recurrence. Unlike other available therapies, allogeneic HCT has the potential to cure up to one half of those transplanted with indolent B-cell non-Hodgkin lymphoma, although the risks need to be recognized and appropriate patient and donor selection is critical to ensure the best outcomes. HCT continues to remain a viable option in the current era of multiple targeted agents.

Phase II Study of Rituximab in Newly Diagnosed Stage IA Nodular Lymphocyte-Predominant Hodgkin Lymphoma (NLPHL): A Report From the German Hodgkin Study Group (GHSG)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2711-2711
Author(s):  
Dennis A. Eichenauer ◽  
Michael Fuchs ◽  
Annette Pluetschow ◽  
Beate Klimm ◽  
Teresa Halbsguth ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Phase Ii ◽  
Overall Response Rate ◽  
Phase Ii Trial ◽  
Progression Free Survival ◽  
Free Survival ◽  
Stage Ia ◽  
Cd20 Antibody ◽  
Anti Cd20

Abstract Abstract 2711 Background: Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare subtype of Hodgkin lymphoma (HL) accounting for about 5% of cases. The clinical course is usually more indolent than in classical HL (cHL) resulting in an excellent long-term prognosis. This is particularly true for patients diagnosed with early-stage NLPHL representing the majority of cases. However, current standard treatment consisting of chemotherapy and/or radiotherapy (RT) is associated with an increased risk of late toxicity. Thus, there is a need for novel treatment strategies. Since CD20 is consistently expressed on the malignant lymphocyte-predominant (LP) cells, anti-CD20 antibody treatment appears to be a promising option. After impressive response rates were reported in relapsed NLPHL patients, the German Hodgkin Study Group (GHSG) initiated a trial to evaluate the anti-CD20 antibody rituximab in newly diagnosed stage IA NLPHL without clinical risk factors. Methods: Between June 2006 and October 2007, 29 patients from 23 sites were enrolled in this multicenter phase II trial. Study entry was restricted to adult patients (age 18 to 75) with biopsy-proven stage IA NLPHL without clinical risk factors. Treatment consisted of four weekly infusions of the anti-CD20 antibody rituximab at a dose of 375 mg/m2. Efficacy endpoints included remission status as assessed by computed tomography (CT) four weeks after completion of treatment, overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) at two years; feasibility endpoints were acute treatment-related toxicities, adverse events, dose reductions and therapy delays. Results: Twenty-eight patients were eligible for the final analysis of this phase II trial; 71.4% of patients were male, 72% had supradiaphragmatic disease and the median age was 40 years. Treatment was conducted in the outpatient setting in the majority of cases. Rituximab was well tolerated; no grade III/IV toxicities were observed. Transfusions of erythrocytes or platelets were not required. At final restaging four weeks after the last rituximab application, 24 patients (85.7%) were in CR/CRu and four patients (14.3%) had partial remission (PR). Thus, overall response rate (ORR) was 100%. After a median follow-up of 43 months, all patients were still alive. Progression-free survival rate estimates at two, three and four years were 85.3%, 81.4% and 77.1%, respectively. Seven patients (25%) have relapsed and two patients developed secondary solid tumors. All patients with NLPHL relapse were successfully salvaged. Conclusions: The results of the present trial confirm the previously reported excellent response of NLPHL patients to rituximab. However, with a relapse rate of 25% at a median observation time of 43 months, rituximab does not seem to be as effective as RT alone or combined-modality strategies in stage IA NLPHL patients. Nonetheless, anti-CD20 antibodies have a favorable toxicity profile and may be offered to selected patients who are at particular risk for long-term side effects such as secondary malignancies. In addition, the combination of anti-CD20 antibodies and chemotherapy may also improve efficacy and decrease toxicity of NLPHL treatment in early unfavorable, advanced or relapsed disease. Disclosures: No relevant conflicts of interest to declare.

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]

Promising Efficacy with the New Anti-CD20 Antibody GA101 In Heavily Pre-Treated NHL Patients – Updated Results with Encouraging Progression Free Survival (PFS) Data From a Phase II Study In Patients with Relapsed/Refractory Indolent NHL (iNHL)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2868-2868 ◽  
Author(s):  
Gilles Andre Salles ◽  
Franck Morschhauser ◽  
Catherine Thieblemont ◽  
Philippe Solal-Céligny ◽  
Thierry Lamy ◽  
...  
Keyword(s):  
Febrile Neutropenia ◽  
Phase Ii ◽  
Single Agent ◽  
Progression Free Survival ◽  
Survival Advantage ◽  
High Dose ◽  
Free Survival ◽  
Cd20 Antibody ◽  
Anti Cd20

Abstract Abstract 2868 Background: GA101 is the first type II, glycoengineered and humanized monoclonal anti-CD20 antibody with Phase I results (NHL/CLL) (Salles, ASH 2008, 2009; Cartron, EHA 2009; Morschhauser, ASH 2009; Sehn, ASH 2009) and phase II results (Indolent NHL) previously reported (EHA 2010). Based on an additional 1 year follow-up period, we report updated efficacy and safety results with single agent GA101, presenting new and encouraging progression free survival (PFS) data indicating a survival advantage of those patients randomized to the high dose cohort (1600/800mg). Methods: 40 eligible patients were randomized to receive GA101 in a low-dose (LD, n=18) or a high dose (HD, n=22) cohort. GA101 was given on d1, d8, d22 and q21 days for total of 9 infusions. In the LD cohort, GA101 was given 400mg all infusions; in the HD cohort, d1 and d8 at 1600mg and 800mg for subsequent infusions. Primary endpoint was end of treatment response (EOR), assessed 4 weeks after last infusion (44 weeks after treatment start). Secondary objectives were safety, pharmacokinetics and PFS. Results: Patients (Table 1) were heavily pre-treated (median 3 prior therapies) with 55% of patients not responding to or relapsing within six months after a previous rituximab-containing regimen (rituximab refractory). There were no significant differences in demographics and baseline tumour burden between the two cohorts and 75% of patients completed all scheduled 9 infusions. EOR was 17% (3 PR, 6 SD, 7 PD, 2 UNK) in the LD cohort, and 55% (2 CR, 10 PR, 6 SD, 4 PD) in the HD cohort. Of note, 6/22 rituximab-refractory patients (5 HD, 1 LD) responded, with a EOR response of 50% in rituximab-refractory patients in the HD cohort (5/10). Responses occurred across all FcγIIIR genotypes in both cohorts: of 3 responders in LD, 2 patients with F/F genotype, other unknown; of 12 responders in HD; 5 F/F, 7 F/V. Responding patients from both LD and HD groups appeared to have higher GA101 plasma concentrations compared to non-responding patients. Median PFS was 6 months [1.1-16.9+ months] and 11.3 months [1.8-14.2+ months] for the LD and HD cohorts respectively (Hazard ratio 0.55 [95% CI 0.24;1.27]). Of 15 responding patients at EOR, 9 have an ongoing response in follow-up (LD=2, HD=7), with 2 PRs converting to CR (LD=1, HD=1) and another PR to CRu (HD). In addition 2 patients (LD=1, HD=1) in follow-up converted from EOR SD to PR, one patient with an ongoing response and the other subsequently relapsing, therefore 10 patients currently have an ongoing response. GA101 was well tolerated in both cohorts with the most common AEs being infusion related reactions (LD 72%, HD 73% of patients), mostly of G1-2. During treatment, related G3-4 hematological AEs were transient neutropenia (n = 3 in HD), febrile neutropenia (n=1 in HD) and thrombocytopenia (n = 1 in HD), four patients experienced at least one G3-4 Infection (LD n=1, HD n=3). Nine patients experienced a total 12 SAEs during treatment period, with 4 related to GA101 (HD n=4; herpes zoster, febrile neutropenia, pancreatitis, neutropenia) and 2 patients in the additional follow-up period, with SAEs of pyrexia (LD) and bacteraemia (HD), both unrelated to GA101. In addition, no B-cell recovery has been observed to date. Conclusion: GA101 single agent is well tolerated, with promising efficacy and provides very encouraging PFS data, in this group of heavily pre-treated relapsed and refractory iNHL patients, indicating a survival advantage for those patients in the HD cohort (1600/800mg). Disclosure: Salles: Roche: Consultancy, Honoraria. Morschhauser:Roche: Consultancy, Honoraria. Wenger:Roche: Employment. Birkett:Roche: Employment. Cartron:Roche: Consultancy, Honoraria; GSK: Honoraria.

A Polymorphism in the C1qA Component of Complement Correlates with Prolonged Complete Remission Following Rituximab Therapy of Follicular Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 778-778 ◽  
Author(s):  
Emilian Racila ◽  
Wen-Kai Weng ◽  
James E. Wooldridge ◽  
Brian K. Link ◽  
Ronald Levy ◽  
...  
Keyword(s):  
Complete Remission ◽  
Follicular Lymphoma ◽  
Single Agent ◽  
Progression Free Survival ◽  
Time To Progression ◽  
Free Survival ◽  
Relative Risks ◽  
Complete Clinical Remission ◽  
Duration Of Response ◽  
Anti Cd20

Abstract There is indirect but intriguing evidence that complement plays a role in the clinical response to rituximab and other mAb-based therapies of cancer. We identified a non-coding polymorphism in the C1qA component of complement that appears to result in a post-translational splice variant of the C1qA protein. We examined this polymorphism in 90 patients with follicular lymphoma who were treated with single agent rituximab to assess whether a correlation exists with clinical efficacy. The presence of an A versus a G allele at the C1qA[276] locus was determined using restriction fragment length polymorphism analysis by investigators blinded to the clinical outcome of the patients. The molecular and clinical data was then analyzed according to C1qA polymorphism, including measurement of radiographic response and duration of response, using methods similar to those used to evaluate the correlation between polymorphisms in CD16/CD32 genes and clinical outcome. No statistically significant difference in response rate was found based on C1qA polymorphism. However, prolonged remission was noted among those subjects that achieved remission (either PR or CR) for individuals who were carriers of the A allele at the C1qA[276] locus (AA or AG) compared to homozygous GG subjects. The strongest correlation was found among those subjects that achieved a complete remission to single agent rituximab. In this group, GG subjects had a time to progression of 250 days, while AA /AG subjects had time to progression of 830 days (HR=4.1, 95% CI=2.1–96.9). Multivariate Cox regression analysis of the joint effects of the C1qA, CD32 and CD16 polymorphisms showed that C1q[276] A allele was an independent factor for good prognosis, while FcgRIIIa 158 phenylalanine carrier and FcgRIIa 131 arginine carrier indicated poor survival. Thus, the relative risk was 0.2 for C1qA[276] AA/AG versus GG after controlling for CD32 and CD16 polymorphisms. The relative risks were 4.8 for CD32 HR versus HH and 6.16 for CD32 RR versus HH after controlling for complement and CD16 polymorphisms. The relative risks were 4.57 for CD16 VF against VV and 3.69 for CD16 FF versus VV after controlling for complement and CD32 polymorphisms. These data suggest polymorphisms in C1qA may impact on duration of response to rituximab therapy of follicular lymphoma. Ongoing studies are expanding this cohort, assessing whether this polymorphism correlates clinically with outcome in other malignancies or with other therapeutic approaches in lymphoma patients, and exploring the functional significance of this C1qA polymorphism. If further studies confirm that C1qA genetic polymorphisms correlate with duration of response to rituximab, it will have major implications on our understanding of the role of complement in the immune response to lymphoma, and on development of the next generation of mAb-based cancer treatments. Total AA+AG GG p (log-rank test) TTP=Median time to progression (days) All Subjects 90 70 20 Responders 59 46 13 CR 27 22 5 TTP Overall 177 173 191 0.64 TTP Responders 352 456 334 0.12 TTP CR 798 830 250 0.007 Complement C1qA polymorphism associates with freedom from progression in follicular lymphoma patients who achieve a CR after anti-CD20 therapy. Progression-free survival logrank curves were plotted by C1qA[276] AA and AG vs GG genotype. Cheson criteria were used to estimate complete clinical remission after one round of anti-CD20 therapy. Complement C1qA polymorphism associates with freedom from progression in follicular lymphoma patients who achieve a CR after anti-CD20 therapy. Progression-free survival logrank curves were plotted by C1qA[276] AA and AG vs GG genotype. Cheson criteria were used to estimate complete clinical remission after one round of anti-CD20 therapy.

scholarly journals Lenalidomide in combination with R-CHOP produces high response rates and progression-free survival in new, untreated diffuse large B-cell lymphoma transformed from follicular lymphoma: results from the Phase 2 MC078E study

2021 ◽  
Vol 11 (9) ◽  
Author(s):  
Sanjal H. Desai ◽  
Betsy LaPlant ◽  
William R. Macon ◽  
Rebecca L. King ◽  
Yucai Wang ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Follicular Lymphoma ◽  
B Cell ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Response Rates ◽  
Free Survival ◽  
Large B Cell Lymphoma ◽  
Large B Cell

AbstractDiffuse large B-cell lymphoma (DLBCL), either concurrent with or transformed from follicular lymphoma (FL) is often excluded from clinical trials. Lenalidomide has response rates of 45% in relapsed transformed DLBCL. Herein we present an analysis of MC078E, a phase II clinical trial testing lenalidomide plus R-CHOP (R2CHOP) for patients with untreated transformed/concurrent DLBCL (NCT00670358). Adult patients with transformed or concurrent DLBCL were included. Patients received six cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) with lenalidomide 25 mg days 1–10 of each cycle. The primary outcome was progression-free survival (PFS) at 24 months. Secondary outcomes were response rates, event-free survival (EFS), and overall survival (OS). Thirty-nine patients were accrued from August 5, 2013 to July 28, 2020 and 33 were eligible by central pathology review. The median age was 64 (24–80) years, 18 (54%) were male, 25 (76%) were concurrent and 8 (24%) were transformed DLBCL. The PFS, EFS, and OS rates at 24 months were 84.4% (CI95: 67.2–94.7%), 84.5% (CI95: 72.9–98%), and 97.0% (CI95: 91.3–100%), respectively. R2CHOP is effective in concurrent and transformed DLBCL. The study supports the inclusion of anthracycline-naive transformed and concurrent DLBCL in future clinical trials of novel immunomodulatory analogues.

Rituximab maintenance for the Treatment of patients with Follicular Lymphoma: Systematic Review and Meta-Analysis of Randomized Trials - 2010 Update.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1798-1798 ◽  
Author(s):  
Liat Vidal ◽  
Anat Gafter-Gvili ◽  
Gilles Salles ◽  
Martin H. Dreyling ◽  
Michele Ghielmini ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Follicular Lymphoma ◽  
Survival Benefit ◽  
Maintenance Treatment ◽  
Randomized Trials ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Free Survival ◽  
Rituximab Maintenance

Abstract Abstract 1798 Rituximab maintenance for the treatment of patients with follicular lymphoma: systematic review and meta-analysis of randomized trials - 2010 update. Liat Vidal, Anat Gafter-Gvili, Gilles Salles, Martin Dreyling, Michele Ghielmini, Shu-Fang Hsu Schmitz, Ruth Pettengell, Mathias Witsenz-Harig, Ofer Shpilberg. Follicular lymphoma (FL) is characterized by slow growth and an initially high rate of response to treatment, but patients typically relapse and experience progressive disease. Rituximab in combination with chemotherapy has been shown to improve overall survival (OS) in patients with FL compared with chemotherapy alone. In order to evaluate the effect of maintenance treatment with rituximab on the OS of patients with FL we performed a systematic review and meta-analysis in 2007. Updated results from these studies and new clinical trials are reported here. Methods: A systematic review and meta-analysis of randomized controlled trials that compared rituximab maintenance therapy with observation or treatment at relapse (no maintenance therapy). In June 2010 we updated our 2007 search in The Cochrane Library, MEDLINE, LILACS, conference proceedings, and databases of ongoing trials. Two reviewers independently assessed the quality of the trials and extracted data. HRs for time-to-event data were estimated and pooled. Results: The search in 2007 identified five eligible trials including 1143 adult patients. The results of the meta-analysis of 985 patients with FL were previously reported. The present search identified six additional included trials; three of them had no current available outcome data. Three of the trials that were included in our first report had long term outcomes that were available for the current meta-analysis. Patients treated with maintenance rituximab had statistically significant better OS compared to patients in the observation arm or patients treated at relapse (HR for death 0.75, 95% confidence interval (CI) 0.61 to 0.91, 2283 patients, Figure). Patients with refractory or relapsed (i.e., previously treated) FL had a significant survival benefit with maintenance rituximab therapy (HR for death 0.72, 95% CI 0.57 to 0.91, 909 patients), whereas previously untreated patients did not (HR for death 0.83, 95% CI 0.56 to 1.23, 1374 patients). Progression free survival was improved in each of the included trials, pooled HR 0.54 95% CI 0.48 to 0.61, n=2283. This effect was consistent both in patients who received rituximab maintenance after their first induction therapy (HR 0.53, 95% CI 0.44 to 0.63, n=1374), and in those who received maintenance rituximab after two or more inductions (HR 0.63, 95% CI 0.50 to 0.79, n=804), and following different induction therapies: rituximab alone (HR 0.54, 95% CI 0.40 to 0.73, n=240), chemotherapy alone (HR 0.49, 95% CI 0.37 to 0.66, n=308), and rituximab-chemotherapy (HR 0.58, 95% CI 0.48 to 0.70, n=1352). The rate of infection-related adverse events was higher with rituximab maintenance treatment (Risk ratio (RR) 1.99, 95% CI 1.21 to 3.27). The rate of grade 3/4 adverse events was higher with rituximab maintenance (RR 1.47 95% CI 1.19 to 1.83). Conclusions: Rituximab maintenance improves OS and disease control in patients with FL after a successful induction therapy. The accumulating data from new and updated clinical trials did not change the results of our former meta-analysis. While a clear survival benefit is shown only for patients with relapsed or refractory FL, progression free survival is improved after first induction as well as after two or more inductions. Disclosures: Salles: Roche: Honoraria. Dreyling:Roche: . Ghielmini:Roche: Consultancy. Pettengell:Roche: Consultancy, Honoraria. Shpilberg:Roche: Consultancy.

I131-tositumomab monotherapy as frontline treatment for follicular lymphoma: Updated results after a median follow-up of 8 years

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8033-8033 ◽  
Author(s):  
M. S. Kaminski ◽  
J. Estes ◽  
M. Tuck ◽  
C. W. Ross ◽  
R. L. Wahl
Keyword(s):  
Follicular Lymphoma ◽  
Single Agent ◽  
Progression Free Survival ◽  
Single Institution ◽  
Free Survival ◽  
Frontline Treatment ◽  
Anti Cd20 ◽  
High Degree ◽  
The Impact

8033 Background: Monoclonal antibody-based therapies are improving the outcome for patients (pts) with follicular lymphoma (FL). Radioimmunotherapy has been found to be effective for pts with relapsed/refractory disease, but even more so when used as frontline treatment. Methods and Results. We previously reported the results of a phase II, single-institution, study of anti-CD20 I-131- Tositumomab (Bexxar) given as a single agent and as a single one-week treatment for 76 pts with Stage 3 or 4 FL (NEJM 352:441, 2005). An overall response (OR) rate and complete remission (CR) rate of 95% and 75%, respectively, were observed. With a median follow-up of 5.1 yrs, 5-yr overall survival (OS) and progression-free survival (PFS) were 89% and 59%, respectively, with a median PFS reached at 6.1 yrs. We now report on this pt cohort after a median follow-up of 7.93 yrs. The 8-year and 10-yr OS is estimated (by KM) now at 86% and 8-yr PFS is 50% (95% CI: 38.8 - 61.7%). Only 3 additional relapses have occurred in the additional follow-up period (at 8.0, 8.3, and 9.2 years) in those with CRs. The 8-yr PFS for the 57 pts who achieved CR is now 64%. The median for PFS has now being reached for CRs at 9.2 yrs. When the impact of baseline FLIPI scores were analyzed, only 8-yr OS was significantly affected when low-risk (LR) and intermediate-risk (IR) categories were combined and compared to the high-risk (HR) category (92% vs. 75%; p = 0.029). The 8-yr PFS for LR + IR pts was 56% vs. 35% for HR pts (p = 0.317). 27 of the 76 total pts (35%) had HR scores. Of additional importance, no cases of MDS or AML have yet been observed. Other longterm toxicities including thyroid status and second non-hematologic cancers will be updated at the meeting. Conclusions. These data underscore the high degree of effectiveness and durability of remissions achieved with a single, one-week course of frontline Bexxar and should serve as a benchmark for comparison to other studies using more prolonged and toxic treatments, including those combining unlabeled or radiolabeled antibodies with chemotherapy. No significant financial relationships to disclose.

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