Cancer Treatment Today » Rituxan

Rituxan or Rituxan with cladribine for Variant Hairy Cell Leukemia – pro

M Levin, MD — Fri, 18 Oct 2013 14:01:45 +0000

Recent literature suggests that a subgroup of Hairy Cell Leukemia(NCL), sometimes called Variant Hairy Cell Leukemia(HCL-V)l my in fact be a different disease not related to HCL at all and which my respond to rituximab to a much higher extent than common Hairy Cell does. It is thought that this variant is what used to be called Leukemic Reticuloendotheliosis in the past. It is an uncommon disorder accounting for approximately 0.4% of chronic lymphoid malignancies and 10% of all HCl cases. In contrast to HCl-C, HCl-V is a more aggressive disease and according to the new WHO classification it is no longer considered to be biologically related to HCl-C. Patients with HCl-V have an elevated white blood count, easy-to-aspirate bone marrow, unlike HCL which is difficult to aspirate, and weak reactivity to tartrate – resistant acid phosphatase (TRAP). Immunophenotypically, HCl-V cells are positive for CD103 and CD11c and negative for CD25. The HCl-V cells express also the B-cell antigens, CD19, CD20 and CD22. The HCl-V patients have frequently an unmutated Ig gene configuration. Currently, the principles of therapy for this rare disease derive from uncontrolled single institutional studies, or even single case reports. In contrast to HCl-C, the HCl-V response to purine nucleoside analogs (PNA) is limited to partial responses in approximately 50% of patients. However, complete responses were observed in patients treated with rituximab and anti-CD22 immunotoxins.

For non-variant type, the use fo the first two together is based on a study reported very recently in ASCO on 3/2020 byKreitmen et al as reported in ASCO 2020. This regimen is for patients who have minimal residual disease after 6 months. In the trial, 68 patients with purine analog-naive classic hairy cell leukemia were randomly assigned to receive 0.15 mg/kg of cladribine intravenously on days 1 to 5 with eight weekly doses of rituximab at 375 mg/m2 started on day 1 (concurrent group, n = 34) or 6 months later after detection of minimal residual disease in their blood (delayed group, n = 34). Minimal residual disease tests included blood and bone marrow flow cytometry and bone marrow immunohistochemistry.

Patients in either group could receive a second course of rituximab 6 months after the first. The primary endpoint was 6-month minimal residual diseasefree complete remission rates with concurrent treatment vs cladribine monotherapy in the delayed group. THe delayed group did better nad ahd less toxicity. In the trial, 68 patients with purine analognaive classic hairy cell leukemia were randomly assigned to receive 0.15 mg/kg of cladribine intravenously on days 1 to 5 with eight weekly doses of rituximab at 375 mg/m2 started on day 1 (concurrent group, n = 34) or 6 months later after detection of minimal residual disease in their blood (delayed group, n = 34). Minimal residual disease tests included blood and bone marrow flow cytometry and bone marrow immunohistochemistry.

Patients in either group could receive a second course of rituximab 6 months after the first. The primary endpoint was 6-month minimal residual disease-free complete remission rates with concurrent treatment vs cladribine monotherapy in the delayed group, which favored the concurrent group, but with more thrmbocytopenia..
The investigators concluded: “Achieving minimal residual disease-free complete remission of hairy cell leukemia after first-line cladribine is greatly enhanced by concurrent rituximab and less so by delayed rituximab. Longer follow-up will determine if minimal residual disease-free survival leads to less need for additional therapy or cure of hairy cell leukemia.”

NCCN lists single-agent cladribine or pentostatin in first line and a purine analog with rituximab for recurrent or refractory disease only. and Elitek, not in combination.

Jones G, Parry-Jones N, Wilkins B, Else M, Catovsky D, British Committee for Standards in Haematology. Revised guidelines for the diagnosis and management of hairy cell leukaemia and hairy cell leukaemia variant. Br J Haematol. 2012 Jan;156(2):186-95. [60 references]

Jones G, Parry-Jones N, Wilkins B, et al. Revised guidelines for the diagnosis and management of hairy cell leukaemia and hairy cell leukaemia variant. Br J Haematol 2012; 156:186.

Hagberg H, Lundholm L. Rituximab, a chimaeric anti-CD20 monoclonal antibody, in the treatment of hairy cell leukaemia. Br J Haematol 2001; 115:609.

Robak T. Current treatment options in hairy cell leukemia and hairy cell leukemia variant. Cancer Treat Rev 2006; 32:365.

Arons E, Suntum T, Stetler-Stevenson M, Kreitman RJ. VH4-34+ hairy cell leukemia, a new variant with poor prognosis despite standard therapy. Blood 2009; 114:4687.

Robak T. Hairy-cell leukemia variant: recent view on diagnosis, biology and treatment. Cancer Treat Rev 2011; 37:3.

Grever MR, Abdel-Wahab O, Andritsos LA, et al. Consensus guidelines for the diagnosis and management of patients with classic hairy cell leukemia. Blood 2017; 129:553.

https://www.ascopost.com/news/march-2020/first-line-cladribine-with-concurrent-or-delayed-rituximab-for-hairy-cell-leukemia/

nccn, hcl-1, A- 2020

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Rituxan for MS and optic neuromyelitis – pro

M Levin, MD — Thu, 13 Sep 2012 17:52:28 +0000

Neuromyelitis Optica, also called Devic’s Syndrome, is similar to multiple sclerosis but more rapidly progressive and affects optic nerves to a greater degree. There is phase II data to support rituxan for multiple sclerosis, primarily from the double-blind, multicenter Helping to Evaluate Rituxan in Relapsing-Remitting Multiple Sclerosis (HERMES) trial. It randomized 104 patients 2:1 to rituximab or placebo. The drug was given at 1,000 mg IV on days one and 15. The study’s primary endpoint was the effect on gadolinium-enhancing lesion counts as seen on MRI brain scans at weeks 12, 16, 20, and 24. and this endpoint was met in favor of the rituximab arm. More than 80% of the rituximab group had no lesions at these evaluations, compared 51.4% of the placebo group (P<0.001).

If these encouraging results are confirmed in a phase III trial, they will establish B cells as a novel cellular target for MS therapy. For neuromyelititis, there is a case series of 8 patients and another one that is a retrospective review of 25 patients. A 2011 Cochrane guideline does not recommend Rituxan for multiple sclerosis. The authors did not find convincing evidence to support rituximab as an effective treatment for RRMS also because the small number of participants and the short term follow-up in the one comparative study of Rituxan vs. placebo. As far as safety is concerned, patients reported infusion-associated adverse events within 24 hours after the first infusion, including headache, back pain, depression, limb pain, general pain, heat sensations, pruritus, and rash.

Jacob A, Weinshenker BG, Violich I, McLinskey N, Krupp L, Fox RJ, Wingerchuk DM, Boggild M, Constantinescu CS, Miller A, De Angelis T, Matiello M, Cree BA. Treatment of neuromyelitis optica with rituximab: retrospective analysis of 25 patients.Arch Neurol. 2008 Nov;65(11):1443-8.

B-Cell Depletion for MS. JWatch Neurology 2008: 1-1

Stephen L. Hauser, M.D., Emmanuelle Waubant, M.D., Ph.D., Douglas L. Arnold, M.D., Timothy Vollmer, M.D., Jack Antel, M.D., Robert J. Fox, M.D., Amit Bar-Or, M.D., Michael Panzara, M.D., Neena Sarkar, Ph.D., Sunil Agarwal, M.D., Annette Langer-Gould, M.D., Ph.D., Craig H. Smith, M.D., for the HERMES Trial Group B-Cell Depletion with Rituximab in Relapsing–Remitting Multiple Sclerosis NEJM Volume 358:676-688 February 14, 2008 Number 7

B. A. Choudry and J. W. Chan
An Update on Monoclonal Antibody Therapies in Multiple Sclerosis
Journal of Pharmacy Practice, April 1, 2007; 20(2): 167 – 180.

B. A.C. Cree, MD, PhD, MCR, S. Lamb, RN, K. Morgan, A. Chen, MD, E. Waubant, MD and C. Genain, MD An open label study of the effects of rituximab in neuromyelitis optica NEUROLOGY 2005;64:1270-1272

Sellner J, Boggild M, Clanet M, Hintzen RQ, Illes Z, Montalban X, Du Pasquier RA, Polman CH, Sorensen PS, Hemmer B.EFNS guidelines on diagnosis and management of neuromyelitis optica. Eur J Neurol. 2010 Jun 7.

Dian He, Hongyu Zhou, Wenjie Han and Shihong Zhang
Cochrane Guideline, Rituximab for relapsing-remitting multiple sclerosis, Article first published online: 11 MAY 2011 |

Mixalis L. KosmidisPractical considerations on the use of rituximab in autoimmune neurological disorders, Ther Adv Neurol Disord. 2010 Mar; 3(2): 93–105.

Rituxan for glomerulonephritis – pro

M Levin, MD — Thu, 13 Sep 2012 17:51:39 +0000

You have glomerulonephritis, a condition characterized by inflammation that attacks the glomeruli, the filter in the kidney that produces the urine. A number of types of glomerulonephritis exist, each of which has different causes, outcomes if not treated, and responses to treatments.

Rituximab is an antibody that destroys specific immune cells that are thought to underlie the development of IMN.

Remuzzi and colleagues reported the results from a study in Italy, in which 8 patients with IMN that had not responded to standard therapies were treated with rituximab. They observed that 1 of the 8 patients had essentially a complete response of disease, and 3 others had substantial improvements in their disease, as evidenced by decreased urinary protein losses. When the authors of this study compared the responses of these 8 patients with those of control patients chosen who had similar baseline conditions, but who were not treated with rituximab, they suggested that treatment with rituximab significantly decreased urine protein losses and improved renal function. Several side effects were seen with rituximab, including laryngeal spasm, chills, and skin rash. While these results are very preliminary and need to be repeated by future studies, they suggest the potential for rituximab to be added to the armamentarium of therapeutic options for IMN. A recent review stated that in total there were 13 case reports, three case series and one prospective study; however there are no comparative studies.

Remuzzi G, Chiurchiu C, Abbate M, Brusegan V, Bontempelli M, Ruggenenti P. Rituximab for idiopathic membranous nephropathy. J Am Soc Nephrol. 2002;13:15A. Abstract F-FC068.

M. S. Ahmed and C. F. Wong
Rituximab and nephrotic syndrome: a new therapeutic hope?
Nephrol. Dial. Transplant., January 1, 2008; 23(1): 11 – 17.

Rituximab for splenic marginal zone lymphoma – pro

M Levin, MD — Thu, 13 Sep 2012 17:48:01 +0000

Splenic marginal zone lymphoma is a relatively new subcategory of non-Hodgkin’s lymphoma that was previously included in the category of splenic B-cell lymphoma. It is CD-20 postive and would be expected torespond to Rituxan, It is a low grade lymphoma and included in the “low grade” category and timing of intervention is similar to patients with chronic lymphocytic leukemia (CLL).
A recent study reported effectiveness in a low number of patients but these are relatively rare diseases. This observation would also be consistent with the treatment of other low-grade NHL entities such as follicular lymphoma.NCCN recommends that it be treated like low-grade follicular lymphoma for which NCCN does list Rituximab.

Tsimberidou AM, Catovsky D, Schlette E, et al. Outcomes of patients with splenic marginal zone lymphoma and marginal zone lymphoma treated with rituximab with or without chemotherapy or chemotherapy alone. Cancer . 2006;107:125-135.

National Institute for Health and Clinical Excellence (NICE). Rituximab for the treatment of follicular lymphoma. London (UK): National Institute for Health and Clinical Excellence (NICE); 2006 Sep. 20 p. (Technology appraisal guidance; no. 110).

nccn.org, non-hodgkin’s lymphoma

Rituxan in polymyositis – pro

M Levin, MD — Thu, 13 Sep 2012 17:46:18 +0000

Polymyositis and dermatomyositis are inflammatory muscle disorders of unknown etiology currently classified under the rubric of idiopathic inflammatory myopathy (IIM). There are case reports and small proseepctive phase II studies and series.

In an open-label uncontrolled pilot study (n = 7), Levine (2005) reported their findings of 7 adult patients with dermatomyositis (DM), 6 of whom had longstanding illness that was responding inadequately to a number of currently available immunosuppressive agents. All patients received 4 intravenous infusions of rituximab given at weekly intervals. Patients were followed up for up to 1 year without further treatment with rituximab. One patient was lost to follow-up. The principal effectiveness outcome was muscle strength, measured by quantitative dynomometry. All 6 evaluable patients exhibited major clinical improvement, with muscle strength increasing over baseline by 36 to 113 %. Maximal improvements in muscle strength occurred as early as 12 weeks after the initial infusion of rituximab. CD20+ B cells were effectively depleted in all patients by 12 weeks. Four patients experienced a return of symptoms that coincided with the return of B cells before the 52-week end point. Two patients maintained their increased muscle strength at 52 weeks, and 1 of these patients maintained this strength even after the return of B cells. Other symptoms of DM (e.g., rash, alopecia, and reduced forced vital capacity) improved markedly in patients with these symptoms. Rituximab was well-tolerated, with no treatment-related severe or serious adverse events during the observation period of this study. The authors concluded that the results of this small open-label study of DM patients treated with rituximab provided sufficiently encouraging results to justify a more formal evaluation of the value of B cell depletion therapy in the treatment of DM. Furthermore, in a review on “B cell-targeted therapy in diseases other than rheumatoid arthritis”, Looney (2005) stated that “depletion of B cells during rituximab therapy was associated with improvement in global disease activity …. further controlled studies are warranted to optimize rituximab as monotherapy and to develop combination therapies in patients with refractory autoimmune diseases”.

In an open-label study, Mok and colleagues (2007) reported the effectiveness and toxicity of rituximab in the treatment of refractory polymyositis. Adult patients with active polymyositis as evidenced by persistent proximal muscle weakness, elevated creatine kinase (CK) level, and features of active myositis on electromyography who were refractory to corticosteroids and at least 2 other immunosuppressive agents were recruited. While immunosuppressive agents were continued, rituximab (375 mg/m2) was given by intravenous infusion weekly for 4 consecutive weeks. Patients were followed-up 4-weekly for serial assessment of muscle power, serum muscle enzymes, physician’s and patient’s global impression of disease activity, disability, and quality of life scores. Four patients (3 women, 1 man) were studied. The mean age was 53 +/- 11 years and the mean duration of polymyositis was 4.8 +/- 3.3 years. All had persistently active myositis for at least 2 years. At Week 28, significant improvement in the mean proximal muscle power scores and reduction in CK levels in comparison to baseline were observed. Two patients had return of full muscle power with significant drop in CK level. There was a trend of improvement in disability scores as well as both the mental and physical components of the Medical Outcomes Study Short Form-36 Health Survey scores. Rituximab was well-tolerated. The authors concluded that rituximab is an option to be considered in refractory polymyositis, however, further controlled trials are needed to confirm its effectiveness.

The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) at the National Institutes of Health is sponsoring the first international multi-center trial to be conducted in both adult and juvenile myositis patients. This multi-center trial (The Rituximab In Myositis (RIM) Study) examines the effectiveness of rituximab, a novel biologic agent. A randomized, double-blind, placebo-phase, multi-centre, phase II trial of intravenous rituximab in the treatment of refractory myositis in adults and children, involving approximately 20 adult centres and 17 paediatric clinical centres in the United States, Canada, United Kingdom, Czech Republic and Sweden will be enrolling a total of 200 participants.

Noss EH, Hausner-Sypek DL, Weinblatt ME. Rituximab as therapy for refractory polymyositis and dermatomyositis. J Rheumatol 2006;33:1021-6.

Levine TD. Rituximab in the treatment of dermatomyositis: an open-label pilot study. Arthritis Rheum 2005;52:601-7.

Mok CC, Ho LY, To CH. Rituximab for refractory polymyositis: An open-label prospective study. J Rheumatol. 2007;34(9):1864-1868.

Chiappetta N, Steier J, Gruber B. Rituximab in the treatment of refractory dermatomyositis. J Clin Rheumatol 2005;11:264-6.

Stringer E, Feldman BM. Advances in the treatment of juvenile dermatomyositis. Curr Opin Rheumatol 2006;18:503-6.

Rituxan for XLP – pro

M Levin, MD — Thu, 13 Sep 2012 17:26:10 +0000

Anti-CD20 (Rituximab) is a humanised monoclonocal antibody directed against the specific CD20 antigens found on B lymphocytes plasma membrane. It has been approved by the FDA for the treatment of lymphoma and post-transplant lymphoproliferative diseases. Its uses in several autoimmune diseases have recently been explored. The rationale for using Rituxan for treating EBV infections in children is that it can destroy B cells and thus “dampen” T-cell response caused by immune dysregulation. After primary infection, patients commonly develop a hemophagocytic syndrome known as fulminant infectious mononucleosis (FIM), which is characterized by the polyclonal expansion of EBV-infected B cells and the dysregulated expansion and activation of T cells and macrophages. FIM leads to hepatic and bone marrow (BM) failure and is fatal in more than 92% of cases.

This is a rare condition and rendomized studies are not possible. The case reports that have been published sugest that it is an effective treatment in an otherwise almost invariably fatal condition.

B.J. Mark, A.P. Knutsen Rituximab Treatment to Control Epstein-Barr Virus (EBV) Infection in X-Linked Lymphoproliferative Disorder (XLP)Volume 117, Issue 2, Supplement, Page S106 (February 2006)

TL Lee, HKW Law, GCF Chan, SY Ha, MHK Ho, KW Chan, YL Lau
Successful Treatment of X-Linked Lymphoproliferative Disease (XLP) with Anti-CD20 Monoclonal Antibody (Rituximab) Followed by Mismatched Unrelated Cord Blood Transplantation HK J Paediatr (New Series) 2006;11:210-214

Michael C. Milone, Donald E. Tsai, Richard L. Hodinka, Lewis B. Silverman, Alejandro
Blood, 1 February 2005, Vol. 105, No. 3, pp. 994-996.

Rituximab in cold agglutinin disease – pro

M Levin, MD — Thu, 13 Sep 2012 17:24:13 +0000

Cold-agglutinin-induced autoimmune hemolytic anemia (AIHA) is difficult to treat. It is also called cold agglutinin disease. Cold agglutinin disease is a group of disorders that are characterized by antierythrocyte autoantibodies that bind red blood cells at cold temperatures (< 37° C), causing hemagglutination. The antibodies are usually of the IgM type but may also be of the immunoglobulin G (IgG) or immunoglobulin A (IgA) type. Symptoms include Raynaud’s phenomena (vasospasm of peripheral arterioles) and acrocyanosis (intra-arteriolar agglutination of red blood cells in the fingers, feet, nose and earlobes, causing numbness, stiffness and pain in these areas). A phase II study of Rituxan is currenlty ongoing in cryoglobulinemia, which is a related disorder.

Rituximab has been used for the treatment of chronic cold agglutinin disease in several case studies and in 1 small trial was 375 mg/m2 weekly for 4 doses. However until a randomized study can be conducted, it remains an investigational option. A 2007 review concluded: “The preliminary results are encouraging, but further studies are required in order to allow firm conclusions.”

Gertz MA. Management of cold haemolytic syndrome. Br J Haematol. 2007;138:422–9.

Massimiliano Palombi, Pasquale Niscola, Alessio Pio Perrotti, and Paolo de Fabritiis Cold autoimmune hemolytic anemia resolved by rituximab Asian J Transfus Sci. 2010 July; 4(2): 136–137

Lee EJ, Kueck B. Rituxan in the treatment of cold agglutinin disease. Blood 1998;92:3490-3491.

Zaja F, Russo D, Fuga G, et al. Rituximab in a case of cold agglutinin disease. Brit J Haematol. 2001;115:232.

Mori A, Tamaru J, Sumi H, Kondo H. Beneficial effects of rituximab on primary cold agglutinin disease refractory to conventional therapy. Eur J Haematol. 2002;68:243-246.

Cohen Y, Polliack A, Zelig O, Goldfarb A. Monotherapy with rituximab induces rapid remission of recurrent cold agglutinin-mediated hemolytic anemia in a patient with indolent lympho-plasmacytic lymphoma. Leuk Lymphoma. 2001;42:1405-1408. Abstract

Sparling TG, Andricevic M, Wass H. Remission of cold hemaggluinin disease induced by rituximab therapy. CMJ. 2001;164:1405.

Engelhardt M. Jakob A, Ruter B, et al. Severe cold hemagglutinin disease (CHD) successfully treated with rituximab. Blood. 2002;100:1922-1923.

Berentsen S, Tjonnfjord GE, Brudevold R, et al. Favourable response to therapy with the anti-CD20 monoclonal antibody rituximab in primary chronic cold agglutinin disease. Brit J Haematol. 2001;115:79-83

G, Fabris M, Ferraccioli G, De Vita S.Rituximab treatment for glomerulonephritis in HCV-associated mixed cryoglobulinaemia: efficacy and safety in the absence of steroids.Rheumatology (Oxford). 2006 Jul;45(7):842-6.
Comment in:
Rheumatology (Oxford). 2006 Jun;45(6):783-4; author reply 784-5

Berentsen S, Ulvestad E, Tjønnfjord GE.B-lymphocytes as targets for therapy in chronic cold agglutinin disease.Cardiovasc Hematol Disord Drug Targets. 2007 Sep;7(3):219-27.

Rituxan for SLE (Lupus) and lupus nephritis – pro

M Levin, MD — Thu, 13 Sep 2012 17:20:05 +0000

Rituxan is offered for lupus nephritis after failing other therapies. Rituxan has been acccepted for treatment of lupus nephritis based on anecdotal data and small prospective studies but a recent study showed that it is ineffective. The trial was conducted by two biotechnology companies, Genentech and Biogen. They annonced the following results in April of 2008.

The trial involved 257 patients, who received either Rituxan or a placebo. Rituxan did not outperform the placebo on seven effectiveness measures used in the trial. A Phase III study of Rituxan® (rituximab) plus mycophenolate mofetil (MMF) and corticosteroids in patients with lupus nephritis did not meet its primary endpoint of significantly reducing disease activity at 52 weeks.

On Dec.18.2006, the U.S. Food and Drug Administration has issued a new warning for Rituxan after the death of two patients with systemic lupus erythematosus (SLE) who were being treated with Rituxan. The cause of death was a brain infection known as progressive multifocal leukoencephalopathy or PML, which had previously been associated with Rituxan in people who were immunosuppressed. Immunosuppression, a condition of decreased immune function, is seen in people with acquired immune deficiency syndrome (AIDS) and in people being treated with immunosuppressant drugs such as methotrexate.

John N. Boletis , Smaragde Marinaki , Chryssanthe Skalioti , Sofia S. Lionaki , Aliki Iniotaki , and Petros P. Sfikakis
Rituximab and mycophenolate mofetil for relapsing proliferative lupus nephritis: a long-term prospective study
NDT Advance Access published on July 1, 2009, DOI 10.1093/ndt/gfp002.
Nephrol. Dial. Transplant. 24: 2157-2160.

D E Furst, E C Keystone, R Fleischmann, P Mease, F C Breedveld, J S Smolen, J R Kalden, J Braun, B Bresnihan, G R Burmester, et al.
Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2009
Ann Rheum Dis, January 1, 2010; 69(Suppl_1): i2 – i29.

Rituxan for pemphigus – pro

M Levin, MD — Thu, 13 Sep 2012 17:16:41 +0000

Pemphigus vulgaris is a potentially fatal autoimmune mucocutaneous blistering disease. Conventional therapy consists of high-dose corticosteroids, immunosuppressive agents, and intravenous immune globulin. More recently newer agenst, such as Cellcept and Dapsone. Among the new approaches is Rituxan. A number of case reprots suggest that Rituxan is an effective reatment but it had not been prospectively studies.For example, a recent report of 11 pateitns treated with Rituxan and IVIG, showed that of 11 patients, 9 had rapid resolution of lesions and a clinical remission lasting 22 to 37 months (mean, 31.1). All immunosuppressive therapy, including prednisone, could be discontinued before ending rituximab treatment in all patients. Two patients were treated with rituximab only during recurrences and had sustained remissions.

Rituxan as been rapidly adopted and is now extensively used. It should be consideeds it appropriate in steroid refractory disease. There are no FDA approved therapies for this disease and Rituxan is off-label.

Harman KE, Albert S, Black MM. Guidelines for the management of pemphigus vulgaris. Br J Dermatol 2003 Nov;149(5):926-37.

Ahmed, A. Razzaque, Spigelman, Zachary, Cavacini, Lisa A., Posner, Marshall R.
Treatment of Pemphigus Vulgaris with Rituximab and Intravenous Immune Globulin
N Engl J Med 2006 355: 1772-1779

Diaz, Luis A. Rituximab and Pemphigus — A Therapeutic Advance N Engl J Med 2007 357: 605-607

Martin LK, Werth VP, Villaneuva EV, Murrell DF. A systematic review of randomized controlled trials for pemphigus vulgaris and pemphigus foliaceus. J Am Acad Dermatol 2011; 64:903.

Martin LK, Werth V, Villanueva E, et al. Interventions for pemphigus vulgaris and pemphigus foliaceus. Cochrane Database Syst Rev 2009; :CD006263.

.Mao X, Payne AS.Seeking approval: present and future therapies for pemphigus vulgaris.Curr Opin Investig Drugs. 2008 May;9(5):497-504

Eming R, Nagel A, Wolff-Franke S, et al. Rituximab exerts a dual effect in pemphigus vulgaris. J Invest Dermatol 2008; 128:2850.

Mouquet H, Musette P, Gougeon ML, et al. B-cell depletion immunotherapy in pemphigus: effects on cellular and humoral immune responses. J Invest Dermatol 2008; 128:2859.

Rituxan for Castleman’s – pro

M Levin, MD — Thu, 13 Sep 2012 17:14:50 +0000

Castleman’s disease, also called angiofollicular lymph node has two forms, localized and a multicentric. The clinical and biological signs are varied and heterogeneous, and the diagnostic is made on the histologic examination. There are no expert assessment, guidelines or consensus statements, policy statements or formal technology assessments for this disease.

Not much has been published about RItuxan in Castleman’s Disease, aside from case reports. Rituximab may be clinically valuable as initial therapy for HIV-associated multicentric Castleman disease. However, in two human immunodeficiency virus-infected patients who needed etoposide therapy to control exacerbations of Castleman disease and received four infusions of rituximab, clinical and virologic relapses with increased blood human herpesvirus-8 DNA levels occurred in both patients 4 and 24 weeks later and were associated with a worsening of Kaposi sarcoma. On the other hand, Rituximab was both effective and safe in a small prosepctive study of HIV-infected patients with chemotherapy-dependent Multicentri Casteleman’s Disease. Since the literature is conflicting and only a small phase II study supports it, Rituxan should be considered experimental at this time.

Bower M, Powles T, Williams S, Davis TN, Atkins M, Montoto S, Orkin C, Webb A, Fisher M, Nelson M, Gazzard B, Stebbing J, Kelleher P. Brief communication: rituximab in HIV-associated multicentric Castleman disease.Ann Intern Med. 2007 Dec 18;147(12):836-9.

Neuville S, Agbalika F, Rabian C, Brière J, Molina JM. Failure of rituximab in human immunodeficiency virus-associated multicentric Castleman disease.Am J Hematol. 2005 Aug;79(4):337-9.

Gérard L, Bérezné A, Galicier L, Meignin V, Obadia M, De Castro N, Jacomet C, Verdon R, Madelaine-Chambrin I, Boulanger E, Chevret S, Agbalika F, Oksenhendler E.Prospective study of rituximab in chemotherapy-dependent human immunodeficiency virus associated multicentric Castleman’s disease: ANRS 117 CastlemaB Trial.Clin Oncol. 2007 Aug 1;25(22):3350-6.