P0286B CELL REPOPULATION AFTER REMISSION INDUCTION WITH RITUXIMAB IN NEWLY DIAGNOSED PATIENTS WITH ANCA-ASSOCIATED VASCULITIS: DOES ONE SIZE FIT ALL?

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Chiara Salviani ◽  
Alessandra Gina Gregorini ◽  
Guido Jeannin ◽  
Federico Alberici ◽  
Giovanni Cancarini ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
B Cell ◽  
Clinical Diagnosis ◽  
Cell Depletion ◽  
Remission Induction ◽  
B Cell Depletion ◽  
Cell Recovery ◽  
Anca Associated Vasculitis ◽  
Cell Repopulation

Abstract Background and Aims Rituximab (RTX) is one of the mainstays of ANCA-associated vasculitis (AAV) treatment. Nevertheless, studies specifically addressing the B cell repopulation in AAV patients after remission induction with RTX are still scanty and with conflicting results. Moreover, the role of B cell monitoring in the management of RTX-based maintenance therapy still remains to be fully elucidated. In this study, we evaluated B cell repopulation after a single course of RTX in treatment-naïve patients with AAV. Method We included all consecutive patients with new diagnosis of AAV from December 2009 to December 2017, treated with a single course of RTX for remission induction, with a follow-up ≥12 months. B cell recovery, re-treatment for relapse or rise in ANCA titer and scheduled re-treatment were considered as the termination of observation period. B cell count was performed by flow cytometry (Beckman Coulter Navios©) every 2 weeks during the 1st month, every 4 weeks until the 6th month, then every 12 weeks. B cell recovery was defined as CD19 count ≥10 cells/μl. Results Seventy-four patients (38% M, 62% F) met the inclusion criteria. Mean age was 63±21 years. MPA, GPA and EGPA were diagnosed in 49 (66%), 24 (33%) and 1 (1%) patients, respectively. ANCA were positive in 65 (88%) patients, with 50 (68%) anti-MPO and 15 (20%) anti-PR3. Overall median follow-up was 40 months (IQR 25-60). All patients achieved remission and complete B cell depletion after RTX. Twenty-two (31%) patients received plasma-exchange and 20 (29%) steroid pulses. Maintenance therapy with azathioprine or methotrexate was started in 10 (14%) patients. Seventeen (23%) patients received re-treatment with RTX (10 patients for relapses, the remaining cases for B cell recovery and/or a rise in ANCA titre or scheduled re-treatment). B cell recovery was observed in 39 (53%) patients, after a median time of 27 months (IQR 20-38). Particularly, only 7% of patients recovered B cells at 12 months (Figure 1). Univariate analysis showed significant correlation of persistent B-cell depletion with diagnosis of MPA vs GPA (p<0.001), ANCA anti-MPO vs anti-PR3 (p=0.009), higher serum creatinine (p<0.0001) and older age (p=0.004) (Figure 2). Sex, plasma-exchange at induction, steroid pulses, cumulative dose of RTX and maintenance therapy did not affect B cell recovery. Multivariate analysis confirmed significant association between B cell recovery and better renal function (RR 2.655, IC 1.254-5.615, p= 0.011) and clinical diagnosis of GPA (RR 2.466, IC 1.211-5.021, p=0.013). Conclusion After a single course of RTX for remission induction, we observed a very long-lasting B cell depletion in the large majority of our patients. Clinical diagnosis of MPA and a worse renal function were significantly correlated to persistent B cell depletion. These data question the need for scheduled RTX re-treatments in all AAV patients regardless of clinical diagnosis and features.

scholarly journals Proteinase-3-anti-neutrophil cytoplasmic antibodies (PR3-ANCAs) predict relapses in ANCA–associated vasculitis patients after rituximab

2020 ◽  
Author(s):  
Laura S van Dam ◽  
Ebru Dirikgil ◽  
Edwin W Bredewold ◽  
Argho Ray ◽  
Jaap A Bakker ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Organ Damage ◽  
Cell Depletion ◽  
Remission Induction ◽  
Proteinase 3 ◽  
B Cell Depletion ◽  
Anca Associated Vasculitis ◽  
Therapeutic Decision Making ◽  
Cell Repopulation

Abstract Background The primary challenge of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) patient care is the early detection of relapses to prevent organ damage and increase survival. Potential biomarkers for relapses are ANCA and B cells, but their predictive value is a matter of debate. Therefore this study investigated how ANCA and B-cell status related to relapses in AAV patients treated with rituximab (RTX) as remission induction (RI). Methods This single-centre cohort study identified 110 ANCA-positive AAV patients treated with RTX between 2006 and 2018. Serial ANCA, CD19+ B-cell status and relapses were assessed >2 years. Results Patients (31/110) relapsed within 2 years after RTX RI treatment. Patients who achieved and maintained PR3-ANCA negativity (n = 29) had few relapses (3%), while persistent proteinase 3 (PR3)-ANCA positivity (n = 49) and reappearance of PR3-ANCAs (n = 10) associated significantly with more relapses (37%, P = 0.002 and 50%, P = 0.002). Patients with incomplete B-cell depletion (n = 11) had significantly more relapses (54%) as compared with patients with B-cell depletion [n = 76 (26%), P = 0.02]. Also, patients with repopulation of B cells (n = 58) had significantly more relapses (41%) as compared with patients without B-cell repopulation [n = 27 (15%), P = 0.03]. Overall, the absence of PR3- or myeloperoxidase (MPO)-ANCA positivity was highly predictive for remaining relapse-free. In PR3-ANCA-positive patients, 96% of the relapses occurred with persistent or reappearance of PR3-ANCAs and 81% with B-cell repopulation. In MPO-ANCA-positive patients, all relapses were restricted to patients with persistent MPO-ANCAs and B-cell repopulation. Conclusions Upon RI treatment with RTX in AAV patients, ANCA and B-cell status were predictive of the majority of relapses and specifically their absence strongly predicted a relapse-free status. Therefore the implementation of ANCA and B-cell monitoring could guide therapeutic decision-making to prevent relapses in AAV patients treated with RTX.

scholarly journals Monitoring B-cell repopulation after depletion therapy in neurologic patients

2018 ◽  
Vol 5 (4) ◽  
pp. e463 ◽  
Author(s):  
Erik Ellwardt ◽  
Lea Ellwardt ◽  
Stefan Bittner ◽  
Frauke Zipp
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Depletion ◽  
Close Monitoring ◽  
B Cell Depletion ◽  
Cell Recovery ◽  
Cell Counts ◽  
White Blood Cell Counts ◽  
Anti Cd20 ◽  
Cell Repopulation

ObjectiveTo determine the factors that influence B-cell repopulation after B-cell depletion therapy in neurologic patients and derive recommendations for monitoring and dosing of patients.MethodsIn this study, we determined the association of body surface area (BSA; calculated by body weight and height with the Dubois formula), sex, pretreatment therapy, age, CSF data, and white blood cell counts with the risk and timing of B-cell repopulation, defined as 1% CD19+ cells (of total lymphocytes), following 87 B cell–depleting anti-CD20 treatment cycles of 45 neurologic patients (28 women; mean age ± SD, 44.5 ± 15.0 years).ResultsPatients with a larger BSA had a higher probability to reach 1% CD19+ cells than those with a smaller BSA (p < 0.05) following B-cell depletion therapy, although those patients had received BSA-adapted doses of rituximab (375 mg/m2). Sex, pretreatment, age, CSF data, or absolute lymphocyte and leukocyte counts during treatment did not significantly influence CD19+ B-cell recovery in the fully adjusted models. Intraindividual B-cell recovery in patients with several treatment cycles did not consistently change over time.ConclusionsB-cell repopulation after depletion therapy displays both high inter- and intra-individual variance. Our data indicate that a larger BSA is associated with faster repopulation of B cells, even when treatment is adapted to the BSA. A reason is the routinely used Dubois formula, underestimating a large BSA. In these patients, there is a need for a higher therapy dose. Because B-cell count–dependent therapy regimes are considered to reduce adverse events, B-cell monitoring will stay highly relevant. Patients' BSA should thus be determined using the Mosteller formula, and close monitoring should be done to avoid resurgent B cells and disease activity.

scholarly journals POS0704 LONG-TERM CLINICAL OUTCOMES OF PATIENTS WITH LUPUS NEPHRITIS TREATED WITH AN INTENSIFIED B-CELL DEPLETION PROTOCOL: A PROSPECTIVE STUDY

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 601.2-601
Author(s):  
D. Roccatello ◽  
S. Sciascia ◽  
C. Naretto ◽  
M. Alpa ◽  
R. Fenoglio ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Maintenance Therapy ◽  
B Cell ◽  
Oral Prednisone ◽  
Standard Of Care ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
A Prospective Study

Background:B cells play a key role In the pathogenesis of Lupus Nephritis (LN).Objectives:we aim to investigate the safety and efficacy of an intensified B-cell depletion induction therapy (IBCDT)without immunosuppressive maintenance regimen compared to standard of care in biopsy-proven LN.Methods:Thirty patients were administered an IBCDT (4 weekly Rituximab 375mg/m2 and 2more doses after 1&2 months;2 infusions of 10 mg/kg cyclophosphamide (CYC),3 methylprednisolone pulses), followed by oral prednisone (tapered to 5 mg/day by the 3rd month). No immunosuppressive maintenance therapy was given. Thirty patients matched for LN class and age were selected as controls: 20 received 3 methylprednisolone pulses days followed by oral prednisone and mycophenolate mofetil (MMF) 2-3 g/day, while 10 were given the Euro Lupus CYC.Results:At 12 months, complete renal remission was observed in 93% of patients on IBCDT, in 62.7% on MMF, and in 75% on CYC (p=0,03); the dose of oral prednisone was lower in the IBCDT group (mean±SD 2.9±5.0mg/dl) than MMF (10.5±8.0 mg/day,p<0.01) or CYC group (7.5±9.0mg/day,p<0.01). Mean follow-up after treatment was 44.5 months (IQR 36–120months), 48.6 months (IQR36–120months), and 45.3 (IQR36–120months) for IBCDT, MMF and CYC, respectively. At their last follow-up visit, we observed no significant differences in proteinuria and serum creatinine, nor in the frequency of new flares among the three groups.Conclusion:In biopsy proven LN, the IBCDT without further immunosuppressive maintenance therapy was shown to be as effective as conventional regimen of MMF or CYC followed by a 3-year maintenance MMF regimen. Moreover, the use of IBCDT was associated with a marked reduction of glucocorticoid cumulative dose.Disclosure of Interests:None declared

B-Cell Depletion and Prevention of Hemolysis in Allogeneic Peripheral Blood Stem Cell Transplantation with Minor ABO Incompatibility.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5151-5151
Author(s):  
Emmanuelle Tavernier ◽  
Anne Thiebaut ◽  
Franck Nicolini ◽  
Quoc Hung Le ◽  
Xavier Thomas ◽  
...  
Keyword(s):  
Stem Cell ◽  
B Cell ◽  
Peripheral Blood Stem Cell ◽  
Ex Vivo ◽  
Median Number ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Abo Incompatibility ◽  
Allogeneic Pbsct

Abstract Immune hemolysis is a severe complication of allogeneic peripheral blood stem cell (PBSC) transplantation with minor ABO-incompatibility, principally observed after conventional allogeneic PBSCT. The B-cell depletion of the PBSC graft is a prophylactic intervention which may decrease incidence and severity of this event. Eight patients who underwent allogeneic PBSCT in our institution between August 1999 and April 2004 were analysed. They all received a B-cell depleted transplantation performed because of minor ABO-incompatibility. There were 5 males and 3 females and the median age was 42.5 years (19–65). The pre-transplant diagnosis were solid tumours for 2 patients and haematological malignancies for 6. All received allogeneic PBSC recruited by G-CSF from 3 HLA identical unrelated and 5 HLA identical sibling donors. The median number of nucleated cells and CD34+ cells harvested were 7.75x108 /Kg (3.9–11) and 6x106/kg (4.3–8.7) and the median number of infused cells were 5.5x108 /Kg (3.4–8.71) and 5x 106/kg (3.1–8.33) respectively. Two patients received myeloablative and 6 patients reduced intensity conditioning regimens (RIC). As graft-versus-host-disease (GVHD) prophylaxis, cyclosporin with methotrexate was given after myeloablative conditioning. After RIC, cyclosporin alone (n=4) or cyclosporin associated to methotrexate (n=1) or cyclosporin associated to mycophenolate mofetil (n=1) were given. The ex-vivo manipulation consisted of a negative CD19 immuno-selection using the Isolex 300 I Baxter procedure. The median number of CD19+ cells (x106/kg) before and after ex-vivo manipulation was respectively 73 and 0.05, which represented a B-cell log depletion of 3.16. The ex-vivo manipulation nevertheless induced a nucleated cell depletion of 20% (from 7.75 x108 cells/kg to 5.52x108 cells/kg after B-cell depletion) and a CD34+ cell loss of 18.5% (from 6x106 cells/kg to 5x106 cells/kg). Engrafment was observed for all patients and median time to neutrophiles (&gt;0.5 G/l) and platelets (&gt;50 G/l) recovery were respectively 19 and 12 days. Acute GVHD occurred for 5 patients whereas 3 patients developed chronic GVHD. At last follow-up, 4 patients died, 3 due to progressive disease, one due to hepatic GVHD. None of these 8 patients developed any clinical severe hemolysis, except one patient who presented a biological hemolysis with the development of a positive antiglobulin test 3 weeks after transplantation, without any consequences. Three months after transplant and at the last follow-up, the 4 long-term alive patients showed a stable erythropoietic reconstitution with an ABO-RhD donor determination. These data indicate that B-cell depletion is an efficient and safe method which could be used in case of minor ABO incompatibility.

Id/KLH Vaccine (FavId™) Following Treatment with Rituximab: An Analysis of Response Rate Improvement (RRI) and Time-to-Progression (TTP) in Follicular Lymphoma (FL).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 587-587 ◽  
Author(s):  
Omer N. Koc ◽  
Charles Redfern ◽  
Peter H. Wiernik ◽  
Fred Rosenfelt ◽  
Jane N. Winter ◽  
...  
Keyword(s):  
T Cell ◽  
Injection Site ◽  
B Cell ◽  
Single Agent ◽  
Injection Site Reaction ◽  
T Cell Response ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Gm Csf

Abstract Background: Id/KLH vaccine (FavId) administered as a single agent has been associated with tumor regressions in patients with relapsed/refractory (RR) FL. B-cell depletion has been demonstrated to augment the T-cell immune response to subsequent vaccine administration in mice (Qin 1998 Nat Med 4:627). Objective: To evaluate the efficacy and safety of Id-KLH administered during the period of rituximab induced B-cell depletion. Eligibility: FL pts who were: treatment naïve (TN); RR following chemotherapy; or relapsed following rituximab. Treatment: Following rituximab (375mg/m2 i.v. weekly x 4) pts received Id-KLH (1 mg s.q. monthly x 6) starting on week 12. GM-CSF, 250 mcg, was administered s.q. at the Id-KLH injection site on days 1–4. Pts could continue Id-KLH until progression. Results: 103 pts received rituximab. Response to rituximab at month 3 was 35% (3-CR; 33-PR). Eleven (11) pts were PD following rituximab (11%). Id/KLH could not be made for 4 pts (4%). Eighty-eight (88) pts were begun on Id-KLH. Among the 45 RR pts, 32 (72%) have not progressed at a median follow-up of 12 months compared with 40% of historical control pts treated with rituximab alone (Witzig 2002 JCO 20:2453). Among the 43 TN pts, 82% have not progressed after a median follow-up of 9 months. RRI (SD to PR, PR to CR after month 3) was observed in 21 pts (12-SD to PR; 9-PR to CR). Robust T-cell responses to both Id and KLH were observed (3 of 3 pts tested). Anti-KLH antibody responses were generally not seen until B-cell recovery. The most frequent adverse event was an injection site reaction. A flu-like syndrome was also observed consistent with GM-CSF administration. Conclusion: Id/KLH vaccine (FavId), administered to pts with FL during a period of B-cell depletion induced by rituximab, can result in an anti-Id T-cell response, and appears to result in an RRI and an increased TTP compared to historical controls. A randomized, double-blind, placebo-controlled, Phase 3 trial of rituximab + FavId has been initiated.

Low doses of humanized anti-CD20 antibody, IMMU-106 (hA20), in refractory or recurrent NHL: Phase I/II results

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8032-8032 ◽  
Author(s):  
F. Morschhauser ◽  
J. P. Leonard ◽  
L. Fayad ◽  
B. Coiffier ◽  
M. Petillon ◽  
...  
Keyword(s):  
Adverse Events ◽  
B Cell ◽  
Serum Levels ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Open Label ◽  
Clear Cut ◽  
Cd20 Antibody ◽  
Anti Cd20

8032 Background: An open-label, multicenter study has shown that the humanized anti-CD20 antibody, IMMU-106 (hA20), which has framework regions of epratuzumab, has a good safety and efficacy profile in NHL pts when administered once-weekly × 4 at different doses. The trial is now focused on confirming the efficacy of lower doses (80–120 mg/m2/wk × 4). Methods: A total of 68 pts (35 male, 33 female; age 34–84) received hA20 at 750 (N=3), 375 (N=27), 200 (N=11), 120 (N=21), or 80 mg/m2 (N=6). They had follicular (FL, N=47) or other (N=21) B-cell NHL, were predominantly stage III/IV (N=47) at study entry, and had received 1–8 prior treatments (median, 2), including 1 (N=40) or more (N=21) rituximab regimens (without progression within 6 months). Results: Sixty- six pts completed all 4 infusions; 1 pt progressed during treatment and withdrew, while another pt with hives and chills after prior rituximab discontinued treatment after a similar episode at 1st infusion. hA20 was generally well tolerated, with shorter infusion times (typically 2 h initially and 1 h subsequently) at lower doses. Drug-related adverse events were transient, Grade 1–2, most occurring only at 1st infusion, and there was no evidence of HAHA in 54 pts now evaluated. Mean antibody serum levels increased with dose and infusions; serum clearance at 375 mg/m2 appears similar to rituximab. Currently, 48 pts with at least 12 wks follow-up were evaluated by Cheson criteria: 32 FL pts had 15 (47%) OR's with 7 (22%) CR/CRu's, even after 2–4 prior rituximab-regimens, and 17 non-FL pts had 6 (38%) OR's, with 1 CRu in a marginal zone NHL pt. At a median follow-up of 11 mo., 9/21 pts with ORs are continuing responses, including 4 long-lived responses (15–20 mo). The evaluated pts include 17 pts at 120 mg/m2 who had 5 (29%) ORs with 3 (17%) CR/CRu's. Responses at 80 mg/m2 remain to be evaluated, but B-cell depletion occurs after the 1st infusion even at this low dose. Conclusions: hA20 appears well-tolerated, with no evidence of significant adverse events other than minor infusion reactions, even at short infusion times. B-cell depletion and responses have occurred at all doses evaluated, with no clear-cut evidence of a dose-response. As such, the study is continuing to confirm the efficacy of lower doses. No significant financial relationships to disclose.

Maintenance therapy using rituximab-induced continuous B cell depletion for ANCA vasculitis

2013 ◽  
Vol 42 (4) ◽  
pp. 774-775
Author(s):  
W. Pendergraft ◽  
F. Cortazar ◽  
J. Wenger ◽  
A. Murphy ◽  
K. Laliberte ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
B Cell ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Anca Vasculitis

scholarly journals Ofatumumab for B cell depletion therapy in ANCA-associated vasculitis: a single-centre case series

Rheumatology ◽  
2016 ◽  
Vol 55 (8) ◽  
pp. 1437-1442 ◽  
Author(s):  
Stephen P. McAdoo ◽  
Rachna Bedi ◽  
Ruth Tarzi ◽  
Megan Griffith ◽  
Charles D. Pusey ◽  
...  
Keyword(s):  
B Cell ◽  
Case Series ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Single Centre ◽  
Anca Associated Vasculitis

B-cell-activating factor receptor expression on naive and memory B cells: relationship with relapse in patients with rheumatoid arthritis following B-cell depletion therapy

2010 ◽  
Vol 69 (12) ◽  
pp. 2181-2188 ◽  
Author(s):  
Inmaculada de la Torre ◽  
Rita A Moura ◽  
Maria J Leandro ◽  
Jonathan Edwards ◽  
Geraldine Cambridge
Keyword(s):  
Rheumatoid Arthritis ◽  
B Cells ◽  
B Cell ◽  
Memory B Cells ◽  
Receptor Expression ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
B Cell Activating Factor ◽  
Significant Difference ◽  
Cell Repopulation

ObjectivesTo examine the expression of B-cell-activating factor receptor (BAFF-R) on naive CD27− and memory CD27+ B cells in normal individuals and patients with rheumatoid arthritis (RA) undergoing B-cell depletion therapy with rituximab.Patients and MethodsBAFF-R expression on B-cell subsets was determined in normal controls (NC; n=11), active patients with RA pre-rituximab (pre-RX; n=15), relapsing patients either concordant for B-cell repopulation (C-R, n=13) or discordant, with relapse more than 3 months after repopulation (D-R, n=11) and patients in remission over 3 months postrepopulation (discordant non-relapsing (D-NR), n=5). Serum BAFF was measured by ELISA and analysed using Mann–Whitney.ResultsThere was no significant difference between NC, pre-RX and D-NR patients in %BAFF-R-positive B cells or mean fluorescence intensity (MFI) in naive and memory B cells. Relapsing patients had significantly lower MFI and %BAFF-R-positive cells in both naive and memory compartments from NC and pre-RX (C-R and D-R; p<0.01). BAFF levels in pre-RX patients were within the normal range and did not correlate with BAFF-R expression in any patient group. D-NR patients had relatively lower proportions of pre and postswitch CD27+ B cells than pre-RX patients (D-NR vs pre-RX; p<0.05 for both) and also lower numbers of postswitch B cells than D-R patients (D-NR vs D-R, p<0.05).ConclusionBAFF-R expression was significantly reduced on both naive and memory B cells in patients at relapse, regardless of the relationship with B-cell repopulation or serum BAFF levels. Re-establishment of active disease was also associated with an increase in class-switch recombination. Factors responsible for lower levels of BAFF-R may relate to altered thresholds for autoreactive B-cell generation at relapse in patients with RA.

Sign in / Sign up

Export Citation Format

Share Document