This site is for New Zealand healthcare professionals. If you are a patient, please click here.

Please enter your email address to view the content of this website.

Not a member? Register
You are here: Home / Our Medicines / MabThera haematology

MabThera haematology

MabThera targets the CD20 antigen to treat non-Hodgkin lymphoma and chronic lymphocytic leukaemia.

mabthera.jpg

Please review the Data Sheet before prescribing.

About MabThera

MabThera is a monoclonal antibody which targets CD20 expressing cells. It is used to treat non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukaemia (CLL).1

MabThera is a Prescription Medicine available as 100 mg/10 mL and 500 mg/50 mL single use vials for intravenous (IV) infusion.

For information on dosage and administration of MabThera, please refer to the Data Sheet on the Medsafe website here.

Medsafe-registered indications

Non-Hodgkin’s lymphoma:

  • CD20 positive, previously untreated low-grade or follicular, B-cell non-Hodgkin’s lymphoma in combination with chemotherapy,
  • CD20 positive, relapsed or chemoresistant low-grade or follicular, B-cell non-Hodgkin’s lymphoma,
  • CD20 positive diffuse large B-cell non-Hodgkin’s lymphoma in combination with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy.
  • Maintenance treatment of patients with CD20 positive, low grade or follicular, B-cell non-Hodgkin’s lymphoma.

Chronic lymphocytic leukaemia

  • Mabthera in combination with chemotherapy is indicated for the treatment of patients with chronic lymphocytic leukaemia (CLL).

MabThera’s Mechanisms of Action

CD20 is a transmembrane surface antigen that appears to be involved in the regulation of B-cell growth and differentiation.2 It is expressed on most malignant B cells as well as mature B cells, but not on stem cells or plasma cells.3

Targeting CD20, therefore, allows for the eradication of target cells and normal B-cell numbers are restored by the continued differentiation of stem cells. B cell numbers return to normal levels within 12 months after completion of therapy. 2

Binding of MabThera to CD20 may lead to the eradication of CD20-positive B cells by a variety of mechanisms: 2,4-6

  • Direct cell death (apoptosis)
  • Antibody-dependent cellular cytotoxicity (ADCC)
  • Complement-dependent cytotoxicity (CDC)
  • Vaccine-like effect

MabThera’s Funding Status

MabThera is listed on the Pharmaceutical Schedule for the treatment of CD20 positive NHL and CLL, under certain criteria.7 Refer to the Schedule for Special Authority information and forms.

Indications funded by PHARMAC7

  • First-line low-grade (indolent) NHL, for up to six treatment cycles
  • Relapsed low-grade (indolent) NHL, after a MabThera treatment-free interval of 12 months or more, for up to six treatment cycles
  • Relapsed low-grade (indolent) NHL, after prior chemotherapy, for up to six treatment cycles
  • First-line aggressive NHL, for up to eight treatment cycles in combination with chemotherapy
  • Relapsed aggressive NHL, after prior chemotherapy, for up to six treatment cycles
  • Relapsed aggressive NHL , after a MabThera treatment-free interval of 12 months or more, for up to four treatment cycles in combination with chemotherapy
  • First-line CLL, in combination with FC chemotherapy, for up to six treatment cycles
  • Relapsed CLL, in combination with FC chemotherapy, where the patient has remained progression free in excess of 36 months from treatment.

Indications not funded by PHARMAC1

  • Relapsed or refractory CLL, where a patient has received prior MabThera and has relapsed within 36 months
  • First-line CLL where the patient has chromosome 17p deletion, or is otherwise ineligible for funded MabThera
  • Maintenance treatment for low-grade or follicular (indolent) NHL.

To assist with the cost of MabThera for unfunded indications, we provide a Cost Share Programme. Please refer to the Cost Share Programme section below for details.

If your patient has private health insurance, it may be worthwhile they check their policy regarding cancer treatments.

References

  1. MabThera® (rituximab) Data Sheet. Available here
  2. Cartron G, Watier H, Golay J, et al. From the bench to the bedside: ways to improve rituximab efficacy. Blood 2004;104:2635–2642.
  3. Glennie MJ, French RR, Cragg MS, et al. Mechanisms of killing by anti-CD20 monoclonal antibodies. Mol Immunol 2007;44:3823–3837.
  4. PHARMAC Pharmaceutical Schedule. Special Authority SA1152 Available here. Accessed 26 May 2016
  5. Weiner GJ. Rituximab: mechanism of action. Semin Hematol 2010; 47:115–123
  6. Cheson BD & Leonard JP. Monoclonal antibody therapy for B-cell non-Hodgkin's lymphoma. N Engl J Med 2008;359:613–626.
  7. Oflazoglu E & Audoly LP. Evolution of anti-CD20 monoclonal antibody therapeutics in oncology. MAbs 2010;2:14–19.

The MabThera Cost Share Programme (MCSP) assists New Zealand patients with the cost of MabThera for unfunded indications in non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukaemia (CLL).The eligibility criteria are:

CLL Cost Share Programme

  • Patient has previously untreated CLL; or
  • Patient has relapsed CLL.

NHL Maintenance Cost Share Programme

  • Patient has received previous induction treatment for untreated low-grade or follicular lymphoma and will be offered 12 cycles of MabThera maintenance over 2 years or until disease progression; or
  • Patient has received previous induction therapy for relapsed low-grade or follicular lymphoma and will be offered 8 cycles of maintenance over 2 years or until disease progression.

If your patients have private health insurance, it may be worthwhile for them to check their policies regarding cancer treatments like MabThera.

Health Insurance Quick Guide

An information booklet for prescribers as well as the enrolment form, claim form and cost calculator are available for download below (click on the images).

MCSP_PrecriberInformation

MabThera Cost Share Programme Information for Prescribers


MabThera Access Programme Cost and Dosing Calculator

MabThera Cost Share Programme Cost and Dosing Calculator


MCSP_EnrolmentForm

MabThera Cost Share Programme Enrolment Form


MCSP_ClaimForm

MabThera Cost Share Programme Claim Form

Low-grade/follicular non-Hodgkin lymphoma (NHL)

A number of large, phase III clinical trials support the use of MabThera in combination with chemotherapy for low-grade/follicular, NHL.1-5


Maintenance therapy for low grade/follicular NHL

The use of maintenance MabThera after induction therapy for previously untreated and relapsed/refractory NHL is supported by a number of large trials.6-9 MabThera maintenance was found to increase progression free survival by up to two years compared to patients who don’t receive maintenance.

Data show that adding MabThera maintenance to induction can delay retreatment and maintain remission.10

This is a conceptual illustration, adapted from Salles et al, 201210

Diffuse large B-cell lymphoma (DLBCL)

Several large, phase III clinical trials support the use of MabThera in combination with CHOP chemotherapy for DLBCL.11-13

Chronic lymphocytic leukaemia (CLL)

The use of MabThera plus chemotherapy for previously untreated and relapsed/refractory CLL is supported by several large clinical trials.14-17

Key Safety Information

Warnings and Precautions:

Infusion-related reactions:

  • Some severe, characterised by pulmonary events and tumour lysis syndrome. Some fatal.
  • Administer appropriate treatments for IRRs. When symptoms resolved, resume at 50% rate.
  • Administer in an environment with full resuscitation facilities.
  • Extreme caution in patients with high tumour burden (CLL & MCL). Possibly split infusion, reduce infusion rate and monitor closely.

Hypersensitivity reactions/Anaphylaxis

  • Medicines to treat hypersensitivity reactions should be available for immediate use.

Pulmonary Events

  • Hypoxia, lung infiltration and acute respiratory failure reported, sometimes preceded by severe bronchospasm and dyspnoea.
  • If severe, interrupt treatment immediately and treat symptoms aggressively.
  • Closely monitor until complete resolution of symptoms.
  • Caution in patients with history of pulmonary insufficiency/pulmonary tumour infiltration.

Rapid Tumour Lysis

  • Consider prophylaxis for patients at risk of TLS.
  • Monitor closely, including appropriate laboratory tests.

Cardiovascular

  • Angina pectoris, arrhythmias, heart failure and MI have occurred in patients treated with MabThera.
  • Consider withholding antihypertensives 12 hours prior to and during infusion.
  • Closely monitor patients with a history of cardiac disease.

Monitoring of blood counts

  • Caution in patients with neutrophils <1.5 x 109/L and/or platelets <75 x 109/L.
  • Consider regular full blood counts.

Infections

  • Do not treat patients with severe active infections.
  • Prior to treatment, screen all patients for HBV.
  • Cases of HBV reactivation and fulminant hepatitis, some of which were fatal.
  • Monitor all patients for infections including reactivation of HBV and PML. Promptly evaluate and treat patients who develop infections.

Progressive Multifocal Leukoencephalopathy (PML)

  • If PML is suspected suspend treatment until PML diagnosis has been excluded; permanently discontinue treatment if PML is confirmed.

Skin reactions

  • SJS and TEN, some with fatal outcome, have been reported.
  • Discontinue if severe skin reactions occur.

Immunisations

  • Complete vaccinations at least 4 weeks prior to treatment.
  • Live virus vaccines not recommended during treatment.

Pregnancy and lactation:

  • Women of childbearing age must use effective contraceptive methods during and for 12 months after treatment with Mabthera.
  • Should not be administered to nursing mothers.

Adverse effects (Very common and common only; See Data Sheet for full list.)

Follicular lymphoma

  • Infections/Infestations: bacterial and viral infections, sepsis, pneumonia, febrile infection, herpes zoster, respiratory tract infection, fungal infections.
  • Blood/lymph: neutropenia, leucopenia, anaemia, thrombocytopenia.
  • Immune system: angioedema, hypersensitivity.
  • Metabolism/nutrition: hyperglycaemia, weight decrease, peripheral and face oedema, increased LDH, hypocalcaemia.
  • Nervous system: paraesthesia, hypoesthesia, agitation, insomnia, vasodilation, dizziness, anxiety.
  • Eye: lacrimation disorder, conjunctivitis.
  • Ear/labyrinth: tinnitus, ear pain.
  • Cardiac: MI, arrhythmia, AF, tachycardia, cardiac disorder.
  • Vascular: hypertension, hypotension, orthostatic hypotension.
  • Respiratory/thoracic: bronchospasm, respiratory disease, chest pain, cough, dyspnoea, rhinitis.
  • GI: nausea, vomiting, diarrhoea, abdominal pain, dysphagia, stomatitis, constipation, dyspepsia, anorexia, throat irritation.
  • Skin/SC: pruritus, rash, urticarial, alopecia, sweating, night sweats.
  • Musculoskeletal/CT: hypertonia, myalgia, arthralgia, back and neck pain, pain.
  • General/administration: fever, chills, asthenia, headache, tumour pain, flushing, malaise, cold syndrome
  • Investigations: decreased IgG levels.

DLBCL

  • Infections/Infestations: bronchitis, acute bronchitis, sinusitis, hepatitis B
  • Blood/Lymph: neutropenia, febrile neutropenia, thrombocytopenia, pancytopenia, granulocytopenia
  • Skin/SC: alopecia, skin disorder
  • General/administration: fatigue, shivering

Please contact the Roche team for further information on the efficacy and/or safety of our products.

References

  1. Marcus R, Imrie K, Solal-Celigny P, et al. Phase III study of R-CVP compared with cyclophosphamide, vincristine, and prednisone alone in patients with previously untreated advanced follicular lymphoma. J Clin Oncol 2008;26:4579–86.23
  2. Hiddemann W, Kneba M, Dreyling M, et al. Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly improves the outcome for patients with advanced-stage follicular lymphoma compared with therapy with CHOP alone: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group.Blood 2005;106:3725–32.
  3. Herold M, Haas A, Srock S, et al. Rituximab added to first-line mitoxantrone, chlorambucil, and prednisolone chemotherapy followed by interferon maintenance prolongs survival in patients with advanced follicular lymphoma: an East German Study Group Hematology and Oncology Study. J Clin Oncol 2007;25:1986–92.
  4. Salles G, Mounier N, de Guibert S, et al. Rituximab combined with chemotherapy and interferon in follicular lymphoma patients: results of the GELA-GOELAMS FL2000 study. Blood 2008;112:4824–31
  5. Schulz H, Bohlius JF, Trelle S, et Al. Immunochemotherapy with rituximab and overall survival in patients with indolent or mantle cell lymphoma: A systematic review and meta-analysis. J Natl Cancer Inst 2007;99:706-714
  6. Forstpointner R, Unterhalt M, Dreyling M, et al. Maintenance therapy with rituximab leads to a significant prolongation of response duration after salvage therapy with a combination of rituximab, fludarabine, cyclophosphamide, and mitoxantrone (R-FCM) in patients with recurring and refractory follicular and mantle cell lymphomas: Results of a prospective randomized study of the German Low Grade Lymphoma Study Group (GLSG). Blood 2006;108:4003–08.
  7. van Oers MH, Klasa R, Marcus RE, et al: Rituximab maintenance improves clinical outcome of relapsed/resistant follicular non-Hodgkin lymphoma in patients both with and without rituximab during induction: Results of a prospective randomized phase 3 intergroup trial. Blood 2006;108:3295-3301
  8. van Oers MH, Van Glabbeke M, Giurgea L, et al. Rituximab maintenance treatment of relapsed/resistant follicular non-Hodgkin’s lymphoma: long-term outcome of the EORTC 20981 phase III randomized intergroup study. J Clin Oncol 2010;28:2853–58.
  9. Salles G, Seymour JF, Offner F, et al: Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial. Lancet 2011;377:42-51,
  10. Salles G, et al. Clinical insights into the use of MabThera/RITUXAN-based treatments for FL. EHA 2012 Satellite Symposium; 1206-030.
  11. Coiffier B, Lepage E, Briere J, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med 2002;346:235–42.
  12. Feugier P, Van Hoof A, Sebban C, et al. Long-term results of the R-CHOP study in the treatment of elderly patients with diff use large B-cell lymphoma: a study by the Groupe d’Etude des Lymphomes de l”Adulte. J Clin Oncol 2005;23:4117–26.
  13. Pfreundschuh MG, Trumper L, Osterborg A et al. CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good prognosis diffuse large B-cell lymphoma—a randomized controlled trial by the Mab Thera International Trial (MinT) Group. Early stopping after the first interim analysis. Lancet Oncol 2006;7:379–391
  14. Hallek M, Fischer K, Fingerle-Rowson G, et al. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia a randomised, open-label, phase 3 trial. Lancet 2010;376:1164-1174
  15. Robak T, Dmoszynska A, Solal-Ce´ ligny P, et al. Rituximab plus fludarabine and cyclophosphamide prolongs progression-free survival compared with fludarabine and cyclophosphamide alone in previously treated chronic lymphocytic leukemia. J Clin Oncol 2010;28:1756-1765
  16. Boettcher S, Ritgen M, Fischer K, et al. Minimal residual disease quantification is an independent predictor of progression-free and overall survival in chronic lymphocytic leukemia: A multivariate analysis from the randomized GCLLSG CLL8 trial. J Clin Oncol 2012;30:980-988
  17. Foon KA, Boyiadzis M, Land SR, et al. Chemoimmunotherapy with low-dose fludarabine and cyclophosphamide and high dose rituximab in previously untreated patients with chronic lymphocytic leukemia. J Clin Oncol 2009;27:498-503
  18. MabThera® (rituximab) Data Sheet.Available here.

This patient booklet contains information on how MabThera works, how it is given, and commonly asked questions. It also includes general information on the medicine such as common side effects, what to do in the event of a side effect and what to expect during treatment.

This booklet has been created to be a helpful source of information that will support patients throughout their treatment. It is not meant to substitute any guidance, advice or help provided by their doctor, nurse or pharmacist.

More information for patients on MabThera can be found at www.cancerinfo.co.nz and in the Consumer Medicine Information (CMI) leaflet, available here.

Click the image below to download the FAQ booklet.

FAQ Booklet


Click the image below to download the patient booklet.

FAQ Booklet

LBC Patient Booklets

Leukaemia and Blood Cancer New Zealand (LBC) have a variety of patient booklets available for download on their website here. The booklets about NHL and CLL include information on what the diseases are, how they are treated, and potential side effects.