Rituximab Injection Research Articles

Treatment of Secondary Central Nervous System Lymphoma with Intrathecal Rituximab, High Dose Methotrexate and R-DHAP, Followed by Autologous Stem Cell Transplantation. A Phase II HOVON Study

AbstractAbstract 306 Introduction.The prognosis of patients with relapsed diffuse large B-cell lymphoma (DLBCL) and central nervous system (CNS) involvement is poor, with a median survival of 2–4 months, and less than 10% 1-year survival. Generally, CNS recurrence is concurrent with or followed soon by systemic relapse or progression. The CNS localization is often meningeal. Therefore, we decided to study the feasibility and efficacy of a new treatment regimen consisting of the standard treatment of relapsed DLBCL (R-DHAP and autologous stem cell transplantation (ASCT)) combined with intrathecal rituximab and high dose methotrexate (MTX) intravenously. Methods.Patients aged 18–65 years with a CNS relapse of DLBCL, based on positive cerebrospinal fluid (CSF) or biopsy proven parenchymal brain localization, with or without systemic progression or relapse, were eligible for our study. Patients with CNS localization based on a typical MRI and concurrent systemic progression or relapse could be included as well. Treatment consisted of 3 cycles of R-DHAP-MTX (dexamethason 40 mg d1-4, cisplatin 100 mg/m2 d1, cytarabine 2 × 2 g/m2 d2, rituximab 375 mg/m2, d5, methotrexate 3 g/m2 d15). Intrathecal rituximab 10 mg was scheduled on d0, followed by 25 mg on day 4, 8, 11 and 21 during cycle 1, and 4 and 3 administrations during cycle 2 and 3, respectively. Patients failing to clear the CSF at the start of cycle 2 could switch to intrathecal methotrexate/cytarabine/dexamethason.In patients with at least a PR and no evidence of lymphoma in bone marrow and CSF after cycle 2, stem cells were harvested after the third R-DHAP cycle. This was followed by MTX cycle 3 and consolidation with busulfan/cyclophosphamide and ASCT. Patients with stable disease or progression, or evidence of lymphoma in the bone marrow or CSF after 2 cycles, went off protocol. Results.36 patients, aged 23–65 year (median age 57) entered the study between May 2007 and April 2011. The CNS relapse was diagnosed 63–3174 days (median 352) after the primary diagnosis. 23 patients had a parenchymal localization on MRI, 16 patients had a positive CSF. At the time of CNS relapse 18 patients had no evidence of systemic relapse. After inclusion of 13 patients, 3 patients had experienced a temporary severe painful radiculopathy after the first intrathecal injection with 25 mg rituximab. Therefore, the study was amended and the dose of all intrathecal rituximab administrations was reduced to 10 mg. After this amendment no more side effects of intrathecal rituximab were observed. 34 patients started the intrathecal rituximab. 14 patients received the planned amount of 12 intrathecal rituximab injections.8/16 patients with positive CSF cleared the CSF from lymphoma before the start of the second R-DHAP. 6/16 failed to clear the CSF from lymphoma, and had to switch to MTX/ARA-C/dexa. 4 of these 6 obtained a negative CSF following this treatment change. 1/16 experienced side effects from rituximab and had to switch to MTX/ARA-C/dexa. In 1/16 patients the CSF response could not be evaluated.After 2 cycles of systemic and intrathecal therapy the CNS response (based on CSF and MRI) was CR or PR in 10 and 13 patients respectively. The overall response rate (including CT and bone marrow) was 53% (19/36), CR rate 28% (10/36). 15 patients (42%) completed treatment according to protocol. The median response duration is 6 months. With a median follow-up of the patients still alive of 20.5 months, the median PFS and OS is 6 and 7 months respectively. PFS at 1 year is 21%, and OS 22%. 20/36 patients died due to NHL, other causes of death were excessive toxicity (n=3), late infection (>3 months after ASCT)(n=2) and unknown (n=2). Conclusion.The combination of R-DHAP-MTX with intrathecal rituximab at a dose of 10 mg is feasible. 25 mg intrathecal rituximab resulted in unacceptable side effects. The outcome of secondary CNS lymphoma following high dose chemotherapy however remains poor, with a median OS of 7 months and a 1-year overall survival of 22%. Disclosures:Off Label Use: intrathecal rituximab.

Vitreoretinal Lymphoma: Changing Trends in Diagnosis and Local Treatment Modalities

To report changing trends in treatment (external beam radiation therapy (EBRT) and intravitreal chemotherapy) from a single institution and report clinical and ocular imaging findings of patients (pts) with vitreoretinal lymphoma (VRL). A retrospective chart review of pts with non-responsive uveitis and vitritis was performed. Only pts with vitreous biopsy proven lymphoma were included. Data recorded included demographics, systemic lymphoma status and treatment, ocular symptoms and clinical findings, optical coherence tomography (OCT), fluorescein angiography (FA) and immunocytological findings, treatment methods intravitreal methotrexate 300 micrograms/0.05 ml, 1000 mcg of rituximab in 0.1 cc and EBRT) and response to treatment. Ocular and systemic lymphoma outcomes at last follow-up visit were also included. Twelve eyes of 8 pts were included in the study. All 8 pts were whites. The mean age of pts was 64.5 years (range 50-83). Central nervous system non-Hodgkin lymphoma (CNS-NHL) was present in 7 of 8 pts (87.5%). Four pts had bilateral disease at presentation (50%). Most common ocular symptoms were diminution of vision in 4 and floaters in 3 pts. Prior to presentation to our center, 50% pts were treated with topical steroids and other 50% did not receive any treatment. Iritis and uveitis were seen in 6 eyes (50%) and vitritis in 11 eyes (91.7%). Retinal infiltrates were present in 8 eyes (66.7%). Two eyes had choroidal lesions (16.7%), of which one was associated with exudative retinal detachment another with papillitis. On OCT, mean central foveal thickness was 270 (range 215-371) μ with presence of cystoid macular edema was present in 2 eyes, subretinal fluid in 1 and pigment epithelial irregularities in 3 eyes. Most common FA findings were macular edema in 6 eyes (60%), perivascular leakage in 2 (20%) and no leakage in 2 eyes (20%). Vitreous biopsy revealed B cell lymphoma in all patients (100%). Immunocytologic analysis in 2 pts showed elevated levels of IL-6 (26.7 pg/ml), IL-10 (12783.5 pg/ml) and IgH gene rearrangement suggestive of lymphoma. Three pts were treated with EBRT (36-45 Gy), of which one had primary VRL. Six eyes were treated with intravitreal methotrexate (range 2-15, mean 9.7). Two pts developed marked keratitis secondary to methotrexate toxicity (33.3%), one of which received intravitreal rituximab injections for persistent vitritis. None developed rituximab related side effects. The mean duration of follow-up was 37.8 months (range 4-96). VRL had resolved in 7 eyes (58.3%) and persistent in 5 eyes (41.7%). Systemic lymphoma was in remission in 5 pts (62.5%). One pt died due to advanced CNS NHL. Intravitreal chemotherapy provided good control rates for VRL pts in our limited series. OCT and FA are superior ocular imaging helpful tools in work-up. Pts with associated CNS NHL had poorer outcomes.

Bcl-6 expression and lactate dehydrogenase level predict prognosis of primary gastric diffuse large B-cell lymphoma

The gastrointestinal tract is the most common site of primary extranodal non-Hodgkin lymphoma, and the prognostic factors of primary gastric diffuse large B-cell lymphoma (PG-DLBCL) differ in various studies. We retrospectively searched for PG-DLBCL in a single institution, performed immunohistochemical analysis, classified tumor phenotype (Hans and Muris algorithms), reviewed medical records, and analyzed the clinical and immunophenotypic variables using Cox proportional hazard regression model. A total of 46 cases were identified including 25 males and 21 females with a median age of 63.5; 18 (39%) were at stage I and 28 (61%) at stage II. Seven (15%) patients underwent surgery as initial treatment including total (n=3, 7%) and subtotal (n=4, 9%) gastrectomy. Thirty-three patients (72%) received frontline chemotherapy treatment including ten with additional rituximab (MabThera) injection, and two (6%) of these patients developed perforation after chemotherapy. Four patients passed away shortly after diagnosis and the remaining three were lost to follow-up. The overall 2- and 5- year survival rates were 55% and 50%, respectively. The expression of various differentiation markers was CD10 (25%), bcl-2 (50%), bcl-6 (84%), and MUM1 (64%). Half of the cases studied (22/44) were classified as germinal center B-cell (GCB) phenotype and the remaining half as non-GCB according to Hans algorithm; 66% and 34% cases belonged to groups 1 and 2, respectively, according to Muris algorithm. Univariate analysis showed the expression of bcl-6 by the tumor cells as a favorable factor, while elevated serum lactate dehydrogenase (LDH) level, bcl-2 expression, and Muris group 2 were associated with poorer outcome. Multivariate analysis revealed that the two prognostic factors were bcl-6 expression and elevated LDH level, with hazard ratios of 0.09 (p=0.002) and 3.72 (p=0.024), respectively. In this retrospective study with heterogeneous treatment modality, we identified bcl-6 expression and elevated LDH level as two prognostic factors for PG-DLBCL.

Efficacy and Complications of Intravitreal Rituximab Injection for Treating Primary Vitreoretinal Lymphoma

To assess the long-term clinical outcomes of intravitreal injections of rituximab (IVR), an anti-CD20 monoclonal antibody, to treat CD20-positive primary vitreoretinal lymphoma (PVRL). Twenty eyes of 13 women (mean age, 66.2 ± 9.9 years) with CD20-positive PVRL were included in this prospective, interventional case series. All patients had discontinued previous intravitreal methotrexate (IVM) treatment because of severe corneal epitheliopathy. Weekly IVR injections (1 mg/0.1 ml) for 4 weeks were administered as a one-course protocol. Additional injections were administered when the PVRL recurred. The effects and the adverse events associated with IVR injections were evaluated. All patients completed a 1-year follow-up (mean observation after IVR injections, 24.7 ± 6.3 months). Before treatment, diffuse keratic precipitates (KPs), anterior vitreous cells, or both were observed in 18 (90%) eyes of 11 patients, and typical subretinal infiltrates were seen in eight (40%) eyes of six patients; all improved with one treatment course. The anterior segment lesions recurred in 11 (55%) eyes of nine patients and resolved with another course of injections. Transient IOP elevations occurred in 12 (60%) eyes of 10 patients within 3.8 ± 1.9 weeks after the first treatment course; iridocyclitis with mutton-fat KPs developed in seven (35%) eyes of six patients with elevated IOP and resolved with topical treatment. No other significant ocular complications or systemic side effects developed. Injections of IVR were shown to be an efficacious alternative treatment for PVRL, although the disease recurred in approximately half of the eyes. Complications included transient IOP elevations and iridocyclitis with mutton-fat KPs that were managed topically. The results of this trial support IVR as one element of combined modality therapy for treating PVRL patients without CNS involvement, particularly for those who respond poorly and have side effects with IVM. (http://www.umin.ac.jp/ctr/ number, UMIN000005604).

Vitreoretinal Lymphoma: Changing Trends in Diagnosis and Local Treatment Modalities at a Single Institution

In this retrospective study on vitreoretinal lymphoma, there was significant change in diagnosis and treatment trends over 17 years at a single institution. Fine needle aspiration biopsy had replaced vitrectomy to collect vitreous sample and external beam radiotherapy in combination with systemic chemotherapy was replaced by intravitreal methotrexate and rituximab, which regressed vitreoretinal lymphoma (VRL) with no relapses or major ocular complications. The purpose of this study was to report the changing trends in treatment (external beam radiotherapy [EBRT] and intravitreal chemotherapy) of VRL and treatment outcomes at a single institution. A retrospective chart review of vitreous biopsy proven patients was performed. The data analysis included demographics, systemic lymphoma status, ocular symptoms, clinical and immunocytological findings, treatment methods, and response (intravitreal methotrexate 300 μg/0.05 mL, 1000 μg/0.1 mL of rituximab and EBRT 36-45 Gy) and ocular and systemic lymphoma outcomes at last follow-up. Twelve eyes of 8 patients had intraocular B-cell lymphoma (median age, 61 years; range, 50-83). Central nervous system non-Hodgkin's lymphoma (CNS-NHL) was present in 7 of 8 patients. Most common ocular symptoms were diminution of vision in 4 and floaters in 3 patients. Iritis and uveitis were found in 6 eyes and vitritis in 11 eyes. Retinal infiltrates were present in 8 eyes. Immunocytology revealed elevated levels of interleukin (IL)-10 (12,783.5 pg/mL), IL-6 (26.7 pg/mL), and IgH gene rearrangement. Three patients were treated with EBRT, 6 eyes with intravitreal methotrexate (median, 9.5; range, 2-15), and 2 eyes with intravitreal rituximab injections (median, 4; range, 2-6). Two patients developed marked keratitis because of methotrexate toxicity. At median follow-up of 33.5 months (range, 4-96), VRL had resolved in 7 eyes and persistent in 5 eyes. One patient died because of advanced CNS-NHL. Intravitreal chemotherapy provided good control rates for VRL patients in our limited series. Patients with associated CNS-NHL had poorer outcomes.

Chronic Antibody-Mediated Rejection Is Reduced by Targeting B-Cell Immunity During an Introductory Period

Transplantation across blood group antigen and human leukocyte antigen (HLA) barriers are immunologically high risk. Both splenectomy and rituximab injection were developed to overcome those immunological barriers. The idea behind these treatments is to control B-cell immunity before and after renal transplantation and antibody production. Between January 2001 and December 2004, recipients underwent pretransplant double-filtration plasmapheresis (DFPP) and splenectomy at the time of transplantation in the ABO-incompatible group (ABO-I-SPX; n= 45). From January 2005 to June 2009, a low dose of rituximab was given as an alternative to splenectomy (ABO-I-RIT; n = 57). As a control group, we selected 83 cases of ABO-C living-donor kidney transplantation between January 2001 and December 2007 (ABO-C). We compared the graft survival rate and chronic antibody-mediated rejection (C-AMR) rate between ABO-C and ABO-I kidney transplantation with induction treatment. C-AMR rates 2 years after the operation were 8.8, 3.5 and 28.9%, and de novo donor-specific anti-HLA antibody (DSHA) positive rates were 2.2, 1.7 and 18.1% in the ABO-I-SPX, ABO-I-RIT and ABO-C groups, respectively. The ABO-C group showed the highest rate of C-AMR and de novo DSHA. B-cell depletion protocols, such as splenectomy or rituximab administration, reduced C-AMR after kidney transplantation.

Clinicopathologic Analysis of Acute Vascular Rejection Cases After Renal Transplantation

IntroductionHistopathologic change of acute vascular rejection (AVR) is characterized by intimal arteritis and transmural arteritis. In this report, we discuss the clinicopathologic analysis of AVR cases after renal transplantation. PatientsAVR was diagnosed in 28 renal transplant recipients followed up in our institute between January 2003 and November 2010. ResultsAmong 28 cases of AVR, 18 were mild (v1 in Banff 07 classification), 8 were moderate (v2), and 2 were severe (v3). Interstitial inflammation was present in 25 biopsy specimens. Moderate to severe tubulitis (t2–t3) was present in 10 biopsy specimens and transplant glomerulitis in 17; peritubular capillaritis was in 25 of the 28 biopsy specimens. C4d deposition in peritubular capillaries was observed in 11/28 cases. By using assays with plastic beads coated with human leukocyte antigen (HLA) in the 28 cases, we detected circulating anti-HLA alloantibody in 18 patients, among which 11/28 were donor-specific. Acute antibody-mediated rejection was diagnosed in 6 cases. Among AVR cases, 19/28 displayed steroid-resistant rejection (SRR) requiring greater anti-rejection therapy (ART), including muromonab CD3 injection, gusperimus injections, plasmapheresis, intravenous immune globulin, and/or rituximab injections. Twenty of 28 patients recovered renal allograft function after ART, and 26/28 grafts are functioning. Among the 2 cases of graft loss, only 1 patient lost his graft due to AVR. ConclusionsIn some cases, AVR might be provoked by anti-donor antibodies. The prognosis of the graft exhibiting AVR was relatively good using available immunosuppression.

Primary and Secondary Ocular Adnexal Lymphoma: A Single Institutional Experience

Abstract 4956 Background:The incidence of ocular adnexal lymphoma (OAL) is rare and usually presents in the setting of central nervous system (CNS) involvement. There are no rigid guidelines for the treatment of OAL, most probably because of the variety of characteristics of the disease. Objectives:To analyze clinical pathological features, therapy and outcomes of patients with primary and secondary OAL. Research Design and Methods:Retrospective chart review of 17 consecutive patients diagnosed with OAL at Moffitt Cancer Center from 2004–2011. Characteristics of the participants were median age 68 years, 15 (88%) white, 2 (12%) Hispanic, and 11 (65%) male. Chlamydia serology testing was negative in all patients tested. Secondary OAL patients were staged per the Ann Arbor Staging System, 2 (22%) stage III and 7 (78%) stage IV. The primary OAL patients were staged utilizing the TNM staging system for OALs (Coupland et al, Arch Pathol Lab Med, 2009). Six (75%) patients were stage T1 and 2 (25%) patients were stage T2. Results:Seventeen patients with a diagnosis of OAL were evaluated in our institution. Patients with OAL are commonly stratified into 2 groups, primary and secondary. Eight (50%) of the patients were diagnosed with primary OAL; of these there were 4 (50%) marginal zone, 3 (37%) diffuse large B cell, and 1 (12%) follicular lymphoma. Nine (50%) patients were diagnosed with secondary OAL; 4 (44%) marginal zone, 1 (11%) diffuse large B cell, 1 (11%) mantle cell, 1 (11%) CLL, and 2 (22%) progressed from low grade to diffuse large B cell lymphoma. In the primary OAL, radiation in combination with systemic chemotherapy was the preferred treatment in diffuse large B cell lymphoma and radiation was preferred in patients with low-grade lymphoma. In secondary OAL, systemic chemotherapy was the preferred treatment for aggressive lymphoma. The choice of systemic Rituximab, radiation, or observation was the preferred treatment of low-grade lymphoma. Aggressive primary OAL had a relapse rate of 2 (66%) patients with a median time to progression of 8 months. Aggressive secondary OAL demonstrated a relapse rate of 50% with median time to progression 6 months. All patients who experienced relapsed disease received salvage chemotherapy. No cases of relapse were observed in the low-grade, primary or secondary, OAL patients. Median duration of response in low-grade primary lymphoma was 6 months and the low-grade secondary lymphoma was 54 months. Conclusion:In our patient population diffuse large B cell lymphoma and marginal zone lymphoma were the most common diagnoses. Ocular adnexal lymphoma has been associated with the presence of CNS disease and it is estimated that 80–90% of patients diagnosed with OAL will experience progression to the CNS. Treatment depends on the extent of disease and the subtype of lymphoma that is histologically identified. Treatment may consist of involved field radiation in localized disease and has approximately less than 10% local recurrence rate. Intravitreal methotrexate and itraorbital injections of Rituximab or a combination of localized radiation and systemic high dose methotrexate are also options for treatment. In the event that there is systemic disease, single agent IV Rituximab or standard chemotherapy regimens such as CHOP-R or CVP-R in conjunction with ocular directed therapy. When disease is localized to the ocular compartment, the burden of disease is low and there is a greater chance of eradicating the disease. The delay in diagnosis increase the risk of CNS involvement and decreases overall survival. Disclosures:No relevant conflicts of interest to declare.

Favorable Impact of Post-ASCT Consolidative Immunotherapy with RITUXIMAB, rINF-a2b and rIL2 on Overall Survival and Progression-Free Survival in Advanced Stage or Relapsed/Refractory Follicular Lymphoma: Results of a Phase II Study

Abstract 3066 Introduction:Advanced stage III/IV or relapsed/refractory follicular lymphoma (FL) can hardly be cured with conventional chemotherapy and patients, even after autologous stem cell transplantation (ASCT), experience innumerable relapse events occurring at decreasing progression-free intervals. Important progress was made since the introduction of RITUXIMAB as part of frontline chemoimmunotherapy or as maintenance after frontline treatment with or without ASCT. But, whatever the policy applied, no plateau is observed regarding overall survival (OS) and progression-free survival (PFS). Disease relapse, even in patients with documented complete remission (CR), is thought to be induced both by resistant minimal residual tumor cells and the lack of immunocompetent mechanisms to contain or eliminate them. Thus, it has been postulated that post-ASCT consolidative immunotherapy might eradicate minimal residual disease, based on antibody-dependent cell-mediated cytotoxicity (ADCC) mechanism, and have a favorable impact on relapse rate and even OS. This view has led to a considerable interest in immunotherapy as a promising therapeutic line to restore and enhance the impaired anti-tumor immune surveillance in the context of post-ASCT low tumor burden. Purpose:We conducted a phase II study to compare OS and PFS between patients with advanced or relapsed/refractory FL receiving consolidative immunotherapy combining recombinant interleukine-2 (rIL-2), recombinant interferon- α-2b (rINF- α-2b) and RITUXIMAB after ASCT, with the aim of controlling minimal residual disease, and other counterparts with FL receiving no further treatment after ASCT. Patients and Methods:From August, 1995, to October, 2009, 139 patients with FL were autografted in complete remission ≥1 or partial remission. Of these patients, 66 were considered eligible for immunotherapy. On adequate post-ASCT hematologic reconstitution, they received 4 weekly IV injections of RITUXIMAB administered on an outpatient fashion. This was followed by a home-based program of subcutaneous injections of rIL2 (6 million UI × 3 / week in 1st cycle; 9 million × 3 / week in 2d) and rINF- α-2b (1.5 million UI × 3 / week in 1st cycle; 3 million × 3 / week in 2d) administered over two 7-week cycles. These two cycles were separated by a two-week free interval. The other 73 patients did not receive any additional treatment after ASCT and served as controls. Results:The two groups were comparable regarding demographic characteristics, disease profile and treatment course, except that the control group had significantly less transformed FL (p =0.0156) and a higher mean treatment line number (p =0.018). Median OS and PFS were not reached in either the study group or the control group. OS, initially not different between the 2 groups (p =0.21), was found significantly higher in the study group after a cut-off follow-up time point of 86.6 months (p =0.017). A significantly higher PFS was also noted in favor of the study group over the control group (p =0.0131). With a median follow-up of 60 months (10 to 136) in the study group and of 82 months (0.7 to 174) in the control group, survival rate was 90.9% and 71.2%, respectively (p= 0.0034) and the overall relapse rate was 19.7% (13 patients) and 41.1% (30 patients), respectively (p= 0.0064). Adverse events were generally mild, consisting essentially of fever and chills with the rIL-2 and rINF- α-2b subcutaneous injections (rapidly controlled with PARACETAMOL), fatigue, grade 2 abnormal liver function tests in one third of patients and grade 2 or 3 cytopenias (anemia or neutropenia) in 40% of patients. Conclusion:These results confirm that post-ASCT immunotherapy with rIL2, rINF- α-2b and RITUXIMAB has a statistically significant impact on OS and PFS. In view of its tolerability, it appears to be quite feasible and safe and might be seen as a promising line of treatment designed for eradicating post-ASCT minimal residual disease and worth being tested within the frame of a randomized trial for validation as an essential step in the treatment algorithm of FL. Disclosures:No relevant conflicts of interest to declare.

Multicenter Phase I Trial of Intraventricular Immuno-Chemotherapy in Recurrent CNS Lymphoma

Abstract 959 Background:We recently studied the safety and activity of intraventricular rituximab monotherapy in the treatment of recurrent intraocular and CNS non-Hodgkin lymphoma (NHL) (JCO 2007 25: 1350–1356). Rapid dissemination throughout the craniospinal axis was demonstrated and cytologic responses were detected in six out of ten patients. Two patients experienced improvement in intraocular NHL and one exhibited resolution of parenchymal NHL. The major goals of this current trial are to perform the first study of intraventricular immuno-chemotherapy in humans and to evaluate the safety of two dose levels of intraventricular rituximab as well as its pharmacokinetics in combination with intraventricular methotrexate (MTX). Secondary goals are to obtain information regarding the efficacy of this approach in the treatment of patients with recurrent CNS lymphoma, (brain parenchyma, intraocular or the leptomeningeal compartment). Methods:Thirteen patients with recurrent/refractory CD20+ CNS NHL were treated at UCSF, Dana Farber Cancer Institute and Massachusetts General Hospital on a phase I clinical trial involving twice weekly intraventricular rituximab at 10 mg and 25 mg dose levels, administered over a planned four week schedule. Rituximab is combined with MTX (12 mg) during the second intraventricular injection each week. Patients achieving partial response or better were eligible for a second month of combination intraventricular rituximab plus MTX. Results:No serious treatment-related toxicity has been detected with intraventricular rituximab/MTX at the 10 mg and 25 mg dose levels. The most common treatment-related toxicity was paresthesias (grade 1). One patient exhibited NHL progression outside of the CNS at three weeks and thus was not evaluable for CNS response, and one patient exhibited stable disease. Complete cytologic responses were detected in ten out of thirteen patients at the one-month restaging. Parenchymal responses were detected in three out of six subjects with one partial response within the corpus callosum, and two complete regressions of lesions within temporal lobe and cerebral cortex. One patient with leptomeningeal lymphoma non-responsive to intravenous rituximab and refractory to high-dose intravenous and intrathecal methotrexate, oral temozolomide and intrathecal liposomal cytarabine, obtained a sustained complete response with the intraventricular rituximab/MTX protocol and subsequently was approved for consolidative autologous stem cell transplant. Two patients have participated in extended dosing on protocol without progression for five and eight months respectively. Thus far, there is no evidence for a relationship between FcGR3A polymorphism and therapeutic resistance in a preliminary analysis (n=8 patients). The maximum tolerated dose of intraventricular rituximab with this combination was established as 25 mg. The mean maximum intraventricular rituximab concentration after intraventricular injection of rituximab was 285 microgram/ml at the 10 mg dose level (N=3) and 882 microgram/ml at the 25 mg dose level (N=10); (p<0.038). The rate of Rituximab clearance from the intraventricular compartment at two hours post injection was 30% slower when administered in combination with methotrexate compared to intraventricular rituximab monotherapy (p <0.02). Conclusions:Intraventricular rituximab/MTX appears to be safe in recurrent CNS NHL. Twelve of thirteen patients completed at least one month of therapy, without any treatment-associated serious adverse events at any of the institutions. Intraventricular administration of methotrexate may significantly attenuate rituximab clearance from the leptomeningeal compartment. There is encouraging evidence for significant activity of intraventricular immuno-chemotherapy in the treatment of drug-resistant CNS NHL, refractory or non-responsive to intravenous rituximab. These results provide strong support for further investigation of this novel therapeutic approach. NCT00221325. Supported by Leukemia and Lymphoma Society and NIH Grant CA13908301. Disclosures:Off Label Use: We will discuss the off-label use of rituximab within the leptomeningeal compartment to treat recurrent/refractory CNS lymphomas. Advani:Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding.

5.14 Rituximab in Allogeneic Hematopoietic Stem Cell Transplantation for Advanced Chronic Lymphocytic Leukemia with Fludarabine Plus Total Body Irradiation Conditioning: Results of a Phase 2 Prospective Multicenter Study (ITAC 02-02)

To evaluate the efficacy and toxicity of an RIC regimen including fludarabine, total body irradiation (TBI), and rituximab for allogeneic hematopoietic stem cell transplantation (HSCT) in patients with stage B or C chronic lymphocytic leukemia (CLL), we conducted this prospective study in adults with CLL who were younger than 65 years, in response after salvage treatment following at least 2 lines of treatment, and had an HLA-identical sibling donor. Conditioning included rituximab 375 mg/m2 on day −5, fludarabine 30 mg/m2 from day −4 to day −2, TBI 2 Gy on day 0, and rituximab 500 mg/m2 on days 1 and 8. Graft-versus-host disease (GVHD) prophylaxis used cyclosporine A (3 mg/kg/d) from day –2 and mycophenolate mofetil (2 g/d) from day 1. Between April 2003 and December 2008, 40 patients were included; 34 (85%) were men and 6 were women. The median age was 54 years (range 35-65 years); 38 (95%) had stage B and 2 had stage C disease. Among 23 patients in whom cytogenetic analysis was done, there were 3 cases of del17, 1 case of trisomy 12, 1 case of t(8-11), and 1 case of del13. Before transplantation, 17 patients received 2 lines of treatment, 10 received 3 lines, 5 received 4 lines, and 8 received more than 4 lines. At allogeneic HSCT, 7 patients (17%) had complete remission, 29 (73%) had partial remission, and 4 (10%) had less than partial remission; 59% were sex-mismatched. For ABO matching, 19% were major incompatible and 13% were minor incompatible. The median interval between diagnosis and allogeneic HSCT was 58 months (range 6-177 months). Seven patients (17%) did not receive rituximab because the protocol did not include it at first and was amended later. Thirty-nine patients (98%) were engrafted, with a median time to neutrophil recovery of 20 days (range 11-70 days), and 79% of patients reached total donor chimerism at day 90. Seventeen patients developed acute GVHD of grade II or greater (8 with grade II, 8 with grade III, and 1 with grade IV), with a cumulative incidence at 3 months of 44% (range 36%-52%). The cumulative incidence of chronic GVHD 29% (range 21%-36%) for lim. and ext. at 12 months and 32% (24%-40%) for lim. and 42% (34%-50%) for ext. at 18 months. After a median follow-up of 28 months (range 3-71 months), median overall survival (OS) was not reached, with 5-year probability of 55% (range 41%-74%). The median event-free survival (EFS) was 30 months (range 15-70 months), with a 5-year probability of 46% (range 33%-66%). The cumulative incidence of relapse at 1 and 3 years was 17% (range 11%-23%) and 22% (range 15%-29%), respectively. The cumulative incidence of transplant-related mortality at 1 and 3 years was 10% (range 5%-15%) and 27% (20%-35%), respectively. Multivariate analysis showed a positive effect of rituximab on OS and EFS (hazard ratios, 0.1 [0-0.6] [p = 0.02] and 0.1 [0-0.4] [p = 0.035], respectively) (Figure). The introduction of rituximab provided a better outcome, especially in terms of acute GVHD. Nevertheless, the incidence of chronic GVHD remained high, leading us to propose increasing the number of rituximab injections after allogeneic HSCT or testing fludarabine/busulfan/antithymocyte globulin plus rituximab.

Evaluation of intraorbital injection of rituximab for treatment of primary ocular adnexal lymphoma: A pilot study

An interventional pilot study to assess the tolerability and activity of the intralesional injection of rituximab, a chimeric mAb that targets the CD20 antigen, in patients with orbital B-cell lymphoma. Five patients received four intralesional injections (one injection a week) of rituximab together with ropivicaine 2%. Side-effects and tumor response were assessed after each injection and during the follow-up (20 months). Two patients obtained complete remission of the intraorbital lesion. Two patients showed incomplete response after induction therapy and received planned escalating rituximab doses, obtaining regression of subjective symptoms. One patient did not achieve tumor regression after the first injection and underwent systemic treatment. This small exploratory study suggests that intralesional rituximab is a well-tolerated treatment for patients with primary ocular adnexal lymphoma. These preliminary findings suggest that intralesional rituximab is a well-tolerated strategy in anterior intraorbital lesion localization of lymphoma.

Transient increases in anti-aquaporin-4 antibody titers following rituximab treatment in neuromyelitis optica, in association with elevated serum BAFF levels

Rituximab is increasingly used for prevention of relapses of neuromyelitis optica (NMO), a condition that is highly associated with serum anti-aquaporin-4 (AQP4) antibodies. However, B-cell depletion also induces systemic B-cell activating factor (BAFF), which may promote antibody production. We collected serial serum samples from a total of seven patients with NMO prior to, and following, treatment with rituximab. The samples were analyzed for anti-AQP4 antibody titer using a cell-based assay and serum BAFF levels were measured on available samples by standard enzyme-linked immunosorbent assay. Anti-AQP4 antibody levels decreased after 4 weeks to 12 weeks from the first injection of rituximab, but they increased transiently in several patients at 2 weeks after the first injection, in association with a parallel increase in serum BAFF levels. Although anti-AQP4 antibodies appear to decrease overall following rituximab treatment, our findings raise concern over the potential for an early BAFF-mediated worsening of patients with NMO receiving rituximab.

Quality of life in 269 patients with poor-risk diffuse large B-cell lymphoma treated with rituximab versus observation after autologous stem cell transplant

We aimed to assess quality of life (QoL) following front-line autologous stem cell transplant (ASCT) and the QoL relationship with rituximab maintenance, in patients with diffuse large B-cell lymphoma. Patients were then randomized to either one weekly rituximab injection for 4 weeks, or observation alone. Patients (n = 269) were given the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaires. Scales for all symptoms exhibited similar temporal patterns, with a marked increase, followed by a plateau after 1 year. The proportion of patients with a clinically significant improvement varied from 6% (constipation) to 56% (fatigue). Age, gender, and previous treatment-induced toxicities were not predictive of variations in QoL. Rituximab significantly reduced pain and symptom severity. Our results for QoL showed that patients experienced rapid recovery after ASCT in all the domains tested. Differences in QoL improvement with time were not connected with rituximab maintenance.

Rituximab in Allogeneic Hematopoietic Stem Cell Transplantation for Advanced Chronic Lymphocytic Leukemia With Fludarabine + Total Body Irradiation Conditioning: Results of a Phase II Prospective Multicenter Study (Itac 02-02)

Abstract 3520 Background: CLL remains incurable with standard therapies. Myeloablative allogeneic SCT (allo-HSCT) is still associated with high TRM and few late relapses. Recently, the major focus of transplantation in CLL has been with reduced-intensity conditioning (RIC) allo-HSCT, which is applicable to the more elderly patient population and which attempts to exploit the graft-versus-leukemia (GVL) effect that was proved in CLL Objective: To evaluate the efficacy and toxicity a RIC regimen including fludarabine and total body irradiation (TBI) with the introduction of rituximab for allo-HSCT in patients with a CLL stage B or C diagnosis. Materials and methods: This prospective study included adult CLL patients with age 70%). Donors were mobilized by G-CSF and in case of collection failure, bone marrow aspiration was authorized. The conditioning included: rituximab 375mg/m 2 on day -5, fludarabine 30 mg/m 2 from day-4 to day-2, TBI 2grays (6-7 cGrays/minute) on day 0 and rituximab 500mg/m 2 on day1 and day8. GVHD prophylaxis used cyclosporine A (IV 3mg/kg/day) from day-2 and mycomofetil fenolate oral (2g/day) from day 1. Results: Between April 2003 and December 2008, 40 patients were included, 34 (85%) males and 6 females with a median age of 54 years (35-65), 38 (95%) were in B stage at diagnosis and 2 in stage C. Among 23 explored for cytogenetics, 8 were abnormal (3 del17, 1 trisomy12, 1 t(8-11) & 1 del13). Before transplantation, 17 patients received 2 lines treatment, 10 three lines, 5 four lines, and 8>4. Only 1 patient received a previous auto-HSCT. Among 18 explored for Matutes status, 1 was in score 1, 1 in score 2, 3 in score 3, 5 in score 4 & 9 in score 5. At time of allograft, 7 (17%) patients were in complete response (CR), 29 (73%) in partial response (PR) and 4 (10%) M). For ABO matching, 68% were compatible, 19% major incomp. & 13% minor incopm. The median interval diagnosis-allo-HSCT was 58 months (6-177). Median CD34+ number was 7.64 (3.1-18.7). Seven (17%) patients did not receive rituximab during conditioning because the protocol did not include it at the beginning and has been amended later. Thirty-nine (98%) patients engrafted with a median time to neutrophils recovery of 20 days (11-70), 79% of patients reached a total donor chimerism at day 90. Seventeen patients developed aGVHD grade ≥II (8 grII, 8 grIII & 1 grIV) with a cumulative incidence at 3 months of 44% (36-52). The cumulative incidence of cGVHD was, at 12 months: 29% (21-36) for limited and extensive; at 18 months: 32% (24-40) limited and 42% (34-50) extensive. After a median follow-up of 28 months (3-71), the median OS was not reached with 3 and 5-years probability of 55%(41-74). The median time of EFS was 30 months (15 - 70) with a 5-years probability of 46%(33-66). The cumulative incidence of relapse at 1 and 3 years was 17% (11-23) and 22% (15-29) respectively. The cumulative incidence TRM at 1 and 3 years was 10% (5-15) and 27% (20-35) respectively. At the last follow-up, 17 patients died, 6 due to relapse and 11 due to TRM. We noticed a high severe infection rate (56%) and 4% of deaths related only to infection. The univariate analysis showed a positive trend of rituximab on OS and relapse, and a significant protective effect on aGVHD>=2 (p=0.02). The multivariate analysis studying age, interval diagnosis-allo-HSCT, ABO and sex matching, disease status at allo-HSCT, CD34+ number, and rituximab, showed a positive significant impact of this last factor (rituximab) on OS and EFS [HR=0.1 [0-0.6] p=0.02 & HR=0.1[0-0.4] p=0.035 respectively]. Conclusion: We showed interesting results in terms of OS, relapse and TRM in patients with advanced CLL after Fludarabine/TBI allo-HSCT. The introduction of rituximab allowed a better outcome especially a significant reduction of incidence and severity of acute GVHD. Nevertheless there was still a high incidence of cGVHD, already known following the Fludarabine/TBI conditioning, leading us to propose either to increase the number of rituximab injections after allo-HSCT, or to test Fludarabine/busilvex/ATG associated to rituximab. Disclosures: No relevant conflicts of interest to declare.

Adapted Management of EBV Reactivation After Solid Organ Transplantation: An Effective Prevention of Post Transplantation Lymphoproliferative Disorders (PTLD). Results of the Largest Prospective Study on 251 Patients

AbstractAbstract 592 Background:PTLD represent a rare but aggressive graft complication. Patients who have received a solid organ transplantation have a 20 to 120 fold higher incidence of non-Hodgkin's lymphoma. EBV reactivation represents a major predictive factor for PTLD, especially during the first year after transplantation, but there is no consensual attitude in this situation Aim:We conducted a monocentric prospective study in the Hospital of Pitie Salpêtriere, Paris, France, on all new heart transplanted patients. EBV viral load (EVL) on whole blood samples was systematically followed and confirmed reactivations were treated depending on viral load. Methods:All heart transplanted patients who had at least one EVL between January 2004 and December 2008 were included. Immunosuppression consisted on anti-lymphocyte sera, ciclosporin, mycophenolate-mofetyl (MM) and prednisone. Twelve to 15 blood samples per year were analysed. If the EVL was more than 105 copies/ml, a CT scan or a PET-san was performed in order to detect any PTLD and patients were treated by diminution of the immunosupression (DIS), mainly by MM arrest. One injection of Rituximab (R) (375 mg/m2) was used in case of failure and/or if EVL was over 106 copies/ml. Results:A total of 251 patients were included, 59 femals/192 men, of a median age of 50 years [16-72]. All but 6 were EBV positive before the graft. Reactivations were detected in 29 cases (11,55%) and treated by DIS only in 20 cases, DIS followed by R in 5 and directly by DIS and R in 4. All EBV negative patients developed a primoinfection in the first year, 2 with an EVL over 105, one presented non documented hepatic lesions which disappeared after DIS. All EBV reactivations were controlled, with a relapse in only one case (reactivations treated the first time by DIS, 10 months later by DIS and R and 6 months later by DIS). With a median follow-up of 1118 days [53-2100] only one PTLD has been diagnosed (in a patient lost to follow up and taken in charge in an other unit) and 24 patients died (9,5%). Analyse of DIS +/− R on graft rejection and potential link between CMV reactivation and EBV reactivation will be presented at the ASH. From 1987 to December 2003, 24 (1,8/year) PTLD have been treated in the same unit (18 EBV positive, 5 negative, 1 unknown), of which 13 were early PTLD (all EBV positive) diagnosed within one year post transplantation. Conclusions:EBV reactivation after organ transplantation can be managed by diminution of immunosupression and/or rituximab, depending on viral load, without serious complication. This adapted management seems to decrease dramatically the incidence of EBV positive PTLD. Disclosures:Choquet:ROCHE: Consultancy. Leblond:ROCHE: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MUNDIPHARMA: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CELGENE: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Post-ASCT Consolidative Immunotherapy with RITUXIMAB, rINF-a2b and rIL2 In Poor-Risk DLBCL: Results of a Phase II Study

AbstractAbstract 3558 Introduction:A minority of patients with diffuse large B cell lymphoma (DLBCL) can really be cured and the early or late relapse rate remains a subject of major concern. The occurrence of disease relapse, even in patients with documented complete remission (CR), is thought to be induced both by resistant minimal residual tumor cells and the lack of immunocompetent mechanisms to eradicate them. Thus, it has been postulated that post-autologous stem cell transplantation (ASCT) consolidative immunotherapy might eradicate minimal residual disease and, therefore, reduce relapse rate and even improve overall survival (OS). This view has led to a considerable interest in immunotherapy as a promising therapeutic line to restore and enhance the impaired anti-tumor immune surveillance in the setting of post-ASCT low tumor burden. Purpose:We conducted a phase II study to compare OS, relapse-free survival (RFS), death rate and overall relapse rate between patients with poor-risk DLBCL receiving consolidative immunotherapy combining recombinant interleukine-2 (rIL-2), recombinant interferon-α-2b (rINF-α-2b) and Rituximab after ASCT, with the aim of controlling minimal residual disease, and other patients with poor-risk DLBCL treated with ASCT alone. Patients and Methods:On 180 patients, 27 with DLBCL from Brest, autografted in complete remission (CR) ≥ 1 or partial remission (PR), were considered eligible for the study. They received, on adequate post-ASCT hematologic reconstitution, 4 weekly IV injections of Rituximab administered on an outpatient fashion. This was followed by a home-based program of subcutaneous injections of rIL2 (6 million UI × 3/week in 1st cycle; 9 million × 3/week in 2d) and rINF-α-2b (1.5 million UI × 3/week in 1st cycle; 3 million × 3/week in 2d) administered over two 7-week cycles. These two cycles were separated by a two-week free interval. One hundred and fifty three patients from Brest, Lille and Tours did not receive any additional treatment after ASCT and served as controls. Results:The two groups were comparable, except for age, which was older in the study group (p=0.018) and for pre-ASCT response pattern, which was better in the control group. There was no influence of recruitment center, sex, disease Ann Arbor stage, IPI score, RITUXIMAB administration before ASCT, graft source or ASCT conditioning regimen on the final results. Median OS and RFS were not reached in any group and are still under study. The median follow-up was 54.9 months in the study group and 48.8 months in the control group. In univariate analysis, the prevalence of death rate was 7.4% and 26.2% in the study group and the control group, respectively (OR = 0.23, 95%CI [0.05-0.99], p=0.03), and the overall relapse rate was 11.1% (3 patients) and 22.9% (35 patients), respectively (OR=0.42, 95%CI [0.12-1.48], p=0.17). In multivariate analysis, the risk of death was significantly decreased (OR 0.196; 95%CI [0.046-0.827] p=0.027) and there was a trend toward a decreased relapse rate (OR 0.348; 95%CI [0.104-1.168], p=0.088) in the study group compared to the control group. In addition, older age was independently associated with an increased risk of death (OR=1.053, 95%CI [1.02-1.09], p=0.002).Adverse events were generally mild, consisting essentially of fever and chills with the rIL-2 and rINF-α-2b subcutaneous injections responding well to PARACETAMOL, fatigue, grade 2 abnormal liver function tests in one third of patients, grade 3 neutropenia in 45% of patients and hypothyroidism in one patient. Conclusion:We found that post-ASCT immunotherapy with rIL2, rINF-α-2b and RITUXIMAB has a statistically significant favorable impact on death rate and a positive, although not statistically significant, effect relapse rate. In view of its toxicity profile, it appears to be quite feasible and safe and might be considered as a promising line of treatment designed for post-ASCT minimal residual disease and worth being evaluated within the frame of a prospective randomized trial. Disclosures:No relevant conflicts of interest to declare.

Rituximab In Allogeneic Hematopoietic Stem Cell Transplantation for Advanced Chronic Lymphocytic Leukemia with Fludarabine + Total Body Irradiation Conditioning: Results of a Phase II Prospective Multicenter Study (ITAC 02-02)

AbstractAbstract 3520 Background:CLL remains incurable with standard therapies. Myeloablative allogeneic SCT (allo-HSCT) is still associated with high TRM and few late relapses. Recently, the major focus of transplantation in CLL has been with reduced-intensity conditioning (RIC) allo-HSCT, which is applicable to the more elderly patient population and which attempts to exploit the graft-versus-leukemia (GVL) effect that was proved in CLL Objective:To evaluate the efficacy and toxicity a RIC regimen including fludarabine and total body irradiation (TBI) with the introduction of rituximab for allo-HSCT in patients with a CLL stage B or C diagnosis. Materials and methods:This prospective study included adult CLL patients with age < 65 years in stage B or C in response after a salvage treatment either following at least 2 treatment lines (1 including fludarabine) or after a progressive disease after auto-HSCT, having a HLA identical sibling donor and a good performance status (Karnfosky >70%). Donors were mobilized by G-CSF and in case of collection failure, bone marrow aspiration was authorized. The conditioning included: rituximab 375mg/m2 on day -5, fludarabine 30 mg/m2 from day-4 to day-2, TBI 2grays (6-7 cGrays/minute) on day 0 and rituximab 500mg/m2 on day1 and day8. GVHD prophylaxis used cyclosporine A (IV 3mg/kg/day) from day-2 and mycomofetil fenolate oral (2g/day) from day 1. Results:Between April 2003 and December 2008, 40 patients were included, 34 (85%) males and 6 females with a median age of 54 years (35-65), 38 (95%) were in B stage at diagnosis and 2 in stage C. Among 23 explored for cytogenetics, 8 were abnormal (3 del17, 1 trisomy12, 1 t(8-11) & 1 del13). Before transplantation, 17 patients received 2 lines treatment, 10 three lines, 5 four lines, and 8>4. Only 1 patient received a previous auto-HSCT. Among 18 explored for Matutes status, 1 was in score 1, 1 in score 2, 3 in score 3, 5 in score 4 & 9 in score 5. At time of allograft, 7 (17%) patients were in complete response (CR), 29 (73%) in partial response (PR) and 4 (10%) < PR. For sex-matching, 59% were mismatched (27%of them were F>M). For ABO matching, 68% were compatible, 19% major incomp. & 13% minor incopm. The median interval diagnosis-allo-HSCT was 58 months (6-177). Median CD34+ number was 7.64 (3.1-18.7). Seven (17%) patients did not receive rituximab during conditioning because the protocol did not include it at the beginning and has been amended later.Thirty-nine (98%) patients engrafted with a median time to neutrophils recovery of 20 days (11-70), 79% of patients reached a total donor chimerism at day 90. Seventeen patients developed aGVHD grade ≥II (8 grII, 8 grIII & 1 grIV) with a cumulative incidence at 3 months of 44% (36-52). The cumulative incidence of cGVHD was, at 12 months: 29% (21-36) for limited and extensive; at 18 months: 32% (24-40) limited and 42% (34-50) extensive. After a median follow-up of 28 months (3-71), the median OS was not reached with 3 and 5-years probability of 55%(41-74). The median time of EFS was 30 months (15 - 70) with a 5-years probability of 46%(33-66). The cumulative incidence of relapse at 1 and 3 years was 17% (11-23) and 22% (15-29) respectively. The cumulative incidence TRM at 1 and 3 years was 10% (5-15) and 27% (20-35) respectively. At the last follow-up, 17 patients died, 6 due to relapse and 11 due to TRM. We noticed a high severe infection rate (56%) and 4% of deaths related only to infection. The univariate analysis showed a positive trend of rituximab on OS and relapse, and a significant protective effect on aGVHD>=2 (p=0.02). The multivariate analysis studying age, interval diagnosis-allo-HSCT, ABO and sex matching, disease status at allo-HSCT, CD34+ number, and rituximab, showed a positive significant impact of this last factor (rituximab) on OS and EFS [HR=0.1 [0-0.6] p=0.02 & HR=0.1[0-0.4] p=0.035 respectively]. Conclusion:We showed interesting results in terms of OS, relapse and TRM in patients with advanced CLL after Fludarabine/TBI allo-HSCT. The introduction of rituximab allowed a better outcome especially a significant reduction of incidence and severity of acute GVHD. Nevertheless there was still a high incidence of cGVHD, already known following the Fludarabine/TBI conditioning, leading us to propose either to increase the number of rituximab injections after allo-HSCT, or to test Fludarabine/busilvex/ATG associated to rituximab. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

EFFECT OF RITUXIMAB ON THE BLOOD CHOLESTEROL TRANSPORT SYSTEM IN PATIENTSWITH RHEUMATOID ARTHRITIS

Система комплексной поддержки и сопровождения научного журнала Elpub позволяет запустить двуязычный сайт журнала со встроенной системой электронной редакции в соответствии с лучшими издательскими практиками, а так же предусматривает техническую и методическую поддержку со стороны специалистов НЭИКОН.

Intralesional Rituximab: A New Therapeutic Approach for Patients with Conjunctival Lymphomas

The tolerability and activity of the intralesional administration of rituximab, a chimeric monoclonal antibody that targets the CD20 antigen, was assessed in patients with conjunctival B-cell lymphoma. The systemic administration of rituximab has varying response rates with different types of lymphoma, generally with a mild toxicity level. Intralesional administration of this drug has increased local disease control in cases of cutaneous mucosa-associated lymphoid tissue (MALT) lymphoma. This was an interventional pilot study of 3 patients with relapsed CD20+ conjunctival lymphomas treated with intralesional injections of rituximab. Two patients with conjunctival MALT lymphoma refractory to previous systemic treatment with rituximab and 1 patient with relapsed follicular lymphoma of the eyelid were included in the study. Patients received 4 weekly intralesional injections followed by 6 monthly injections of undiluted rituximab together with xylocaine 2%. Side effects and tumor response were assessed before each intralesional injection and at 3-month intervals after treatment conclusion. The 2 conjunctival MALT lymphoma patients achieved complete remission after intraconjunctival rituximab treatment, which shows that this method of administration can overcome the primary resistance to this monoclonal antibody. The patient with the eyelid follicular lymphoma did not achieve tumor regression after the first intralesional injections of rituximab. In this patient, the addition of autologous serum resulted in lymphoma remission at the end of treatment, suggesting that drug inefficacy can be related to the low bioavailability of effectors in the tumor tissue. Although follow-up is still short, these preliminary findings suggest that intralesional rituximab is a well-tolerated strategy in marginal-zone and follicular lymphomas of the conjunctiva. An increased bioavailability of effectors in the tumor tissue, by means of the addition of autologous serum, may improve rituximab activity. This strategy could be used in other extranodal CD20+ indolent lymphomas to improve local control, even in patients who are initially refractory to systemic rituximab treatment.