rituximab biosimilar / Viropro, Assertio - LARVOL DELTA

PROTEOMICS MARKERS PROGNOSTIC FOR OUTCOME OF CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS UNDER TREATMENT; RESULTS FROM THE HOVON-109 STUDY (EHA 2019) - "Since many CLL cases show discordant prognostic factors, the identification of new parameters able to relate disease stage and clinical outcome is important to further improve treatment efficacy.Aims To examine the prognostic ability of a) known proteomics markers measured pre-treatment; with special interest in previously identified B-cell activation markers (sCD23, sCD27, CXCL13), and b) to search for new proteomics markers that might be related to treatment response.Methods Study subjects were treated in the HOVON-109 clinical study (a phase I/II trial in 63 CLL patients designed for efficacy and safety of first-line therapy involving chlorambucil, rituximab and lenalidomide). Added prognostic value of the potential proteomics markers compared with a basic model including gender and IGHV status was evaluated, showing a significant independent effect on EFS for especially sCD23, SPINT1, and LY9 (Figure).Conclusion Our study suggests a possible prognostic role for sCD23..."

Clinical • IO Biomarker

A PHASE II TRIAL OF RITUXIMAB/LENALIDOMIDE FOLLOWED BY LENALIDOMIDE MAINTENANCE IN UNTREATED AND RELAPSED INDOLENT LYMPHOMA: LONG TERM FOLLOW UP AND CORRELATIVE ANALYSIS (ICML 2019) - "Rituximab plus lenalidomide followed by lenalidomide maintenance is effective and associated with acceptable toxicity in patients with both previously untreated and R/R advanced stage indolent NHL. This regimen produces durable remissions, even in previously treated patients, with some lasting greater than 10 years. Increased INF-γ, IL-2, CXCL-10, GM-CSF, T cells and decreased B cell levels correlated with response."

Clinical • P2 data

RA PATIENTS’ PERSPECTIVES ON BIOLOGICAL DMARD-INDUCED ADVERSE DRUG REACTIONS AND THEIR BURDEN (EULAR 2019) - " In the Dutch Biologic Monitor 583 consecutive (44.8%) RA patients were included (71.2% female, average age 59 years, SD±12.4) using the originator or a biosimilar of etanercept (ETN, 265), adalimumab (ADA, 196), tocilizumab (41), abatacept (35), certolizumab pegol (23), rituximab (19), infliximab (18), golimumab (15), sarilumab (2), secukinumab (1), anakinra (1). Almost half of the RA patients reported bDMARD-induced ADRs. From the patients’ perspective INJ reactions have the highest prevalence with a relatively low burden, whereas INFs and headache are less prevalent but give the highest burden of the analysed ADRs. Further studies are required to obtain more insight into the perceived differences in ADRs between bDMARDs."

Adverse drug reaction • Clinical

Long-term tolerability, safety and efficacy of rituximab in neuromyelitis optica spectrum disorder: a prospective study. (PubMed, J Neurol) - "Rituximab treatment is well tolerated, safe, and efficacious with a minor risk of mild infusion reactions for NMOSD patients."

Clinical • Journal

Role of Infliximab in Immune Check Point Inhibitor Induced Pneumonitis (ATS 2019) - "...Immune checkpoint inhibitors administered included cytoxic T lymphocyte-4 (CTLA-4) with ipilimumab in 1, programmed cell death-1 (PD-1) with nivolumab in 2 and combination therapy CTLA-4 and PD-1 (ipilumumab and nivolumab) death-ligand 1 in 1...All received only one dose of infliximab, and one patient received other immunosuppressant including cyclophosphamide and rituximab... Pneumonitis related to checkpoint inhibitor therapy can be challenging to treat. After concomitant infection, thromboembolic disease, airway exacerbation and pulmonary embolism are excluded or addressed, steroid therapy is administered. In those without improvement or clinical worsening, infliximab may be a potential option."

Mistaken Identity - Right Treatment for Wrong Disease (ATS 2019) - "...She was treated with methylprednisolone 1g/day for the three days followed by 1mg/kg/day along with broad-spectrum antibiotics...While non-organ threatening disease can be treated with prednisone and methotrexate, organ dysfunction and life-threatening disease require pulse dose steroids with either cyclophosphamide or rituximab. Patients with rapidly declining renal dysfunction or pulmonary alveolar hemorrhage or concomitant Anti-GBM Ab positivity would benefit from plasma exchange. Presence of granuloma in the biopsy from either kidney or lung differentiates GPA from MPA."

ANTIPROLIFERATIVE AND VASOACTIVE TREATMENT MODALITIES IN 457 CONSECUTIVE PATIENTS WITH SYSTEMIC SCLEROSIS FROM ACADEMIC CENTERS IN GREECE (EULAR 2019) - "Methotrexate was the most frequent antiproliferative agent ever administered (53% of patients, 55% of them with diffuse SSc) followed by cyclophosphamide (26%, 78% of them diffuse), mycophenolate (11%, 63% of them diffuse), azathioprine (10%, 64% of them diffuse), rituximab (9%, 84% of them diffuse) and tocilizumab (3%, 68% of them diffuse). About 20% of contemporary SSc patients, including patients with pulmonary fibrosis and digital ulcers, have never received antiproliferative or vasoactive therapy, possibly reflecting the spectrum of benign disease and/or a subgroup of under-treated patients."

Clinical

CLINICAL SPECTRUM AND TREATMENT OF THE RELAPSING POLYCHONDRITIS: A SERIES OF 12 CASES (EULAR 2019) - "...Infliximab was the first biological line in all the cases (100%). Other biological therapies used, in order of frequency, were: adalimumab (25%), rituximab (25%) and tocilizumab (12.5%)... RP is a rare disease with a broad spectrum of clinical expression, which often requires intensive management to control its manifestations, potentially serious when there is involvement of the tracheobronchial tree or is associated with other autoimmune diseases. A large part of our patients require biological therapy at some point in their evolution. References"

Clinical

THE LUNG IN SJÖGREN’S SYNDROME PATIENTS – AN OVERVIEW OF CLINICAL CHARACTERISTICS AND DISEASE OUTCOME (EULAR 2019) - "...One received cyclophosphamide (CYC), 2 azathioprine (AZA) and 4 mycophenolate mofetil (MMF)...Rituximab (RTX) was given to 1 pt with refractory arthritis and new ILD onset...At this point pirfenidone was added to RTX, with clinical improvement... Lung involvement occurred in 12.4% of our cohort and was associated with older disease at pSS diagnosis and presence of constitutional involvement. Small airways disease and ILD had nearly the same prevalence and in the ILD sub-group, NSIP was the commonest pattern. Despite the small number of ILD pts receiving immunosuppression, these drugs seemed to be associated with disease stabilization in most of them."

Clinical

USE,EFFICACY AND LONG TERM SAFETY OF RITUXIMAB IN PEDIATRIC RHEUMATIC DISEASES: SINGLE CENTER EXPERIENCE FROM NORTH INDIA (EULAR 2019) - "... USE: Rituximab was given to 4 children with polyarticular juvenile idiopathic arthritis(PJIA)(4/145=2.7%) and 17 children with pSLE(17/225=7.5%).In children with PJIA, RTX was used as third line treatment, who failed methotrexate and TNF inhibitor therapy...Three(17.6%) flared and required cyclophosphamide/second cycle of RTX. Mean dose of prednisolone prior to RTX was 0.7mg/kg/day while that at 1 year post RTX was 0.065mg/kg/day(p value 0.001) and at 2 years was 0.05mg/kg/day(p value 0.003). We conclude that RTX is efficacious for use in severe spectrum of pSLE and is relatively safe to use even in a developing country like ours with huge infectious disease burden."

Clinical

PRESENTATION, MANAGEMENT AND OUTCOME OF ANCA ASSOCIATED VASCULITIDES IN ITALY: A 20-YEAR FOLLOW-UP STUDY (EULAR 2019) - "The first line IS treatment administered was: cyclophosphamide (CYC) in 66 (38%), rituximab (RTX) in 14 (8%), azathioprine (AZA) in 27 (16%), methotrexate (MTX) in 25 (14%) and mycophenolate (MMF) in only 5 (3%). Our cohort is characterized by significant higher rate of AAV diagnosis in the last decade and this could reflect the increasing incidence and prevalence reported in literature 1 . Interestingly, GPA diagnosis, especially with cANCA/PR3 specificity, was prevalent in our cohort despite some authors reported an higher prevalence of MPA in Mediterrean area 1-2 . Finally, EGPA confirmed a better outcome at last follow up than GPA and MPA, but we noted that no renal and GI involvement was observed in our EGPA patients."

INTERSTITIAL LUNG DISEASE – A RARE MANIFESTATION OF MICROSCOPIC POLYANGIITIS (EULAR 2019) - "All patients received induction therapy with glucocorticosteroids combined with cyclophosphamide, rituximab, azathioprine or methotrexate. ILD is a rare manifestation of MPA, which can precede systemic manifestations. ANCA-associated vasculitis should be included in the spectrum of differential diagnosis in patients with ILD."

HCV-RELATED MIXED CRYOGLOBULINAEMIA IN THE DIRECT-ANTIVIRAL AGENTS ERA: IS THERE ADVANTAGE IN SEQUENTIAL THERAPY WITH RITUXIMAB? (EULAR 2019) - "DAA treatment is associated with rapid and sustained decrease in the level of cryoglobulins and related clinical improvement, specifically purpura. Patients who had been pre-treated with RTX showed clinical improvement in terms of purpura and arthralgia, albeit transient; subsequent treatment with DAA did not result in any immediate or long term additional clinical benefit."

A Case of Empyema Neccessitans Caused by Nocardia Cyriacigeorgica (ATS 2019) - "...He was self-medicating with daily dexamethasone for pain relief. His past medical history was significant for Waldenstrom's Macroglobulinemia for which he completed 5 cycles of Bendamustine and Rituximab, one year prior to hospitalization...He stabilized on intravenous Meropenem and Trimethoprim-Sulfamethoxazole...Although pulmonary involvement of Nocardia is well known, formation of empyema is very rare. Further, there are no known cases Nocardia cyriacigeorgicacausing pulmonary empyema with chest wall involvement and musculoskeletal destruction."

Clinical

Refractory Ebstein Barr Virus Infection and Its Complications in Granulomatosis with Polyangiitis (ATS 2019) - "Introduction : We present a rare case of granulomatosis with polyangiitis (GPA) being treated with azathioprine, complicated by post-transplant lymphoproliferative disorder (PTLD)-like disease and Hemophagocytic Lymphohistiocytosis (HLH) secondary to an Ebstein Barr virus (EBV) infection...Despite high doses of steroids and Rituximab our patient did not show any signs of clinical improvement...And published data regarding PTLD, suggests an overall mortality rate between 65-75 %. It is fair to say that in patients with a combination of PTLD & HLH mortality rates are astronomical and early diagnosis is of paramount importance."

The Diagnostic Challenge of Nonspecific Interstitial Pneumonia in a Pediatric Patient (ATS 2019) - "...Bronchoalveolar lavage grew Aspergillus glaucus, thought to be a contaminant given worsening of symptoms on voriconazole...The patient received treatment with high dose intravenous steroids, mycophenolate mofetil, rituximab and intravenous immunoglobulin in addition to broad-spectrum anti-infectives...Our patient represents a unique case because the clinical history and pathologic findings were not strongly suggestive of other disease processes such as chronic hypersensitivity pneumonitis or connective tissue disease-associated-ILD, and she rapidly progressed to end-stage lung disease that was unresponsive to a variety of treatments. Clinicians should consider NSIP when evaluating children with subacute pulmonary symptoms and complete a full diagnostic workup for associated conditions."

Clinical

Dual-Positive Myeloperoxidase and Proteinase 3 Antibody-Associated Vasculitis Precipitated by Crack-Cocaine Use (ATS 2019) - "...ANCA positivity may be induced by chronic infection with M. tuberculosis and hepatitis C virus (HCV), as well as drugs such as levamisole-adulterated cocaine...Methylprednisolone was re-initiated at 60 mg every six hours and rituximab 375 mg/m2 was administered. Her oxygen requirement decreased and prednisone was tapered...Appropriate diagnosis and treatment were challenging in light of a negative ANCA screen and the paucity of data regarding the significance of dual-positivity of these antibodies. Marked clinical improvement was observed following immunosuppressive therapy."

Patient with Known Rheumatoid Arthritis Presenting with ANCA-Associated Vasculitis Complicated by Diffuse Alveolar Hemorrhage and Acute Respiratory Distress Syndrome (ATS 2019) - "Due to her hemoptysis and CT chest findings, the patient was started on 500mg of methylprednisolone empirically for DAH.Subsequent urgent bronchoscopy with serial lavage confirmed DAH, and patient was pulsed for 3 days with 1 gram of methylprednisolone. She had multiple positive auto-antibodies with concern for microscopic polyangiitis and lupus nephritis in addition to her RA. Despite pulse dose steroids, the patient progressed rapidly to severe acute respiratory distress syndrome requiring intubation and was successfully treated with plasmapheresis and rituximab."

Clinical

Granulomatosis with Polyangiitis Mimicking Empyema and Lung Abscess (ATS 2019) - "She was transitioned to rituximab with continued clinical improvement, and discharged home. After a negative infective workup, necrotizing granulomas and positive serum C-ANCA pulse dose steroids were started with prompt clinical improvement. This case highlights the importance of maintaining a broad differential for cavitary lesions, including vasculitis."

Disseminated Adenovirus Resulting in ARDS Treated with Veno-Venous Extracorporeal Membrane Oxygenation and Brincidofovir (ATS 2019) - "There are no proven pharmacological treatment options for adenovirus, however intravenous immunoglobulin (IVIG), cidofovir, and brincidofovir are sometimes administered.A 44-year-old man with fulminant multiple sclerosis previously treated with high dose steroids, rituximab, and more recently, ocrelizumab and plasmapheresis presented to the ER with fevers, pharyngitis, dyspnea, myalgias, and diarrhea. The patient was extubated 4 days later. Serum adenovirus viral load had decreased to 1890 copies/ml by extubation.This case illustrates disseminated adenovirus in an immunocompromised patient resulting in severe ARDS and renal failure, that was successfully treated with very low tidal volume ventilation while on VV-ECMO in combination with the antiviral drug, Brincidofovir."

Survival of Patients with Acute Exacerbations of Rheumatoid Arthritis Associated Interstitial Lung Disease (ATS 2019) - "Patients who received standard care (steroids, broad spectrum antibiotics, diuretics) had significantly worse six-month survival than those who received more advanced therapies such as extracorporeal membrane oxygenation, plasma exchange, or extra immunosuppression with agents such as rituximab and intravenous immunoglobulin (figure 1). AE-RA-ILD has a prognosis that is comparable to AE-IPF. Risk factors for AE-RA-ILD mortality include requirements for advanced methods of O2 delivery and extensive GGO on HRCT. Women tend to have more severe manifestations and greater mortality."

Clinical

Clinical, Immunological, and Genetic Features in Patients with Activated PI3Kδ Syndrome (APDS): a Systematic Review. (PubMed, Clin Rev Allergy Immunol) - "Immunosuppressive agents such as rituximab, tacrolimus, rapamycin, and leniolisib were also administered for autoimmunity and inflammatory complications. It should be suspected in patients with history of recurrent respiratory infections, lymphoproliferation, and raised IgM levels. Moreover, HSCT should be considered in patients with severe and complicated clinical manifestations with no or insufficient response to the conventional therapies."

Clinical • Journal • Review

Neuromyelitis optica spectrum disorder with increased aquaporin-4 microparticles prior to autoantibodies in cerebrospinal fluid: a case report. (PubMed, J Med Case Rep) - "Microparticles of aquaporin-4 represent subcellular arrangements that may influence the pathogenesis of neuromyelitis optica spectrum disorders and may serve as biomarkers for the underlying cellular disturbances. The increase of aquaporin-4 microparticles in cerebrospinal fluid may be used for early diagnostic purposes; for prevention; and for evaluation of effective treatment, long-term follow-up studies, and elucidating the pathophysiology in neuromyelitis optica spectrum disorders. Further studies of aquaporin-4 microparticles in cerebrospinal fluid of patients with neuromyelitis optica and similar neuropsychiatric disorders are thus called for."

Biomarker • Clinical • Journal

Zevalin-Containing Nonmyeloablative Conditioning for Stem Cell Transplantation (SCT) (clinicaltrials.gov) - P2; N=20; Completed; Sponsor: M.D. Anderson Cancer Center; Active, not recruiting ➔ Completed; Trial completion date: Aug 2019 ➔ Apr 2019; Trial primary completion date: Aug 2019 ➔ Apr 2019

Trial completion • Trial completion date • Trial primary completion date

European myeloma network recommendations on diagnosis and management of patients with rare plasma cell dyscrasias. (PubMed, Leukemia) - "...For patients with WM, the combination of rituximab with chemotherapy remains the treatment cornerstone, while the Bruton-tyrosine kinase inhibitor ibrutinib has been introduced and approved for relapsed/refractory disease...Further aggregation of misfolded light chains could be prevented by doxycycline or monoclonal antibodies targeting amyloid deposits. Initial treatment generally consists of melphalan/dexamethasone or bortezomib-based regimens. For relapsing patients, one can consider proteasome inhibitors, immunomodulatory agents, melphalan or daratumumab...Patients not eligible for transplant procedures require personalized, intensive therapeutic approach. Allogeneic stem cell transplantation can be used in selected patients."

Clinical • Journal • Review