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Gazyva

GAZYVA is an anti-CD20 therapy for first line chronic lymphocytic leukaemia.

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Please review the Data Sheet before prescribing.

Gazyva

GAZYVA is the first glycoengineered, type 2 monoclonal antibody which targets CD20 expressing cells.1 It is registered by Medsafe in combination with chlorambucil for previously-untreated chronic lymphocytic leukaemia (CLL).1

GAZYVA’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.2 B cell numbers return to normal levels within 12 months after completion of therapy.

The CD20 antigen is also not internalised by the cell upon antibody binding, thus allowing the initiation of immune processes.2

GAZYVA is a recombinant monoclonal humanised and glycoengineered type 2 anti-CD20 antibody of the IgG1 isotype.1 Binding of GAZYVA to CD20 may lead to the eradication of CD20-positive B cells by a variety of mechanisms:

  • Enhanced direct cell death induction, an internal cell killing mechanism that is different to apoptosis: GAZYVA inhibits the proliferation of malignant B cells, as well as inducing direct cell death in vitro.3,4
  • Antibody-dependent cellular cytotoxicity (ADCC): GAZYVA binds strongly to Fc receptors on human effector cells, such as macrophages, granulocytes and natural killer (NK) cells, inducing ADCC to destroy target cells.5 GAZYVA has up to a 35-fold increase in ADCC over MabThera.6
  • Complement-dependent cytotoxicity (CDC): GAZYVA directly binds to the C1q complement factor, inducing the complement-dependent activation of macrophages, granulocytes and natural killer cells, resulting in the cell-mediated lysis or phagocytosis of target cells. GAZYVA induces low degrees of CDC activity.6

To download a brochure about GAZYVA's mechanisms of action, click here.

GAZYVA’s Funding Status

GAZYVA is a funded medicine for first line CLL under Special Authority for patients who meet predefined criteria. GAZYVA is unfunded for NHL.

We also provide a Cost Share Programme to assist with the cost of GAZYVA for CLL or NHL patients who do not meet predefined criteria. 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 like GAZYVA.

References

  1. GAZYVA® (obinutuzumab) Data Sheet. Available here.
  2. Klein C, Lammens A, Schäfer W, et al. Epitope interactions of monoclonal antibodies targeting CD20 and their relationship to functional properties. mAbs 2013;5:22-33.
  3. Patz M, Isaeva P, Forcob N, et al. Comparison of the in vitro effects of the anti-CD20 antibodies rituximab and GA101 on chronic lymphocytic leukaemia cells. Br J Haematol 2011;152:295-306.
  4. Mössner E, Brünker P, Moser S, et al. Increasing the efficacy of CD20 antibody therapy through the engineering of a new type II anti-CD20 antibody with enhanced direct and immune effector cell–mediated B-cell cytotoxicity. Blood 2010;115:4393-4402.
  5. Lim SH, Beers SA, French RR, et al. Anti-CD20 monoclonal antibodies: historical and future perspectives. Haematologica 2010;95:135-143.
  6. Cartron G, Watier H, Golay J, et al. From the bench to the bedside: ways to improve rituximab efficacy. Blood 2004;104:2635-2642.
  7. Glennie MJ, French RR, Cragg MS, et al. Mechanisms of killing by anti-CD20 monoclonal antibodies. Mol Immunol 2007;44:3823-3837.


The GAZYVA Cost Share Programme assists with the cost of GAZYVA for New Zealand patients who do not qualify for funding in NHL or CLL under Special Authority.

For information on the Cost Share Programme, please contact us here.

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

Health Insurance Quick Guide

The pivotal study, CLL11, investigated the safety and efficacy of GAZYVA-plus-chlorambucil versus chlorambucil-alone and versus MabThera ® (rituximab)-plus-chlorambucil in 781 patients with comorbidities and previously untreated CLL.1,2

The key efficacy results from the CLL11 study are:

  • 77.3% of patients had a partial or complete response to GAZYVA-plus-chlorambucil compared to 31.4% with chlorambucil-alone.1
  • 22.3% of patients who received GAZYVA-plus-chlorambucil went into complete remission compared to no patients who received chlorambucil-alone.1
  • Patients on GAZYVA-plus-chlorambucil experienced 29.9 months median progression free survival compared to 11.1 months with chlorambucil-alone. That is more than double the progression free survival patients would have anticipated with chlorambucil-alone.2
  • At nearly 3 years of follow up, GAZYVA-plus-chlorambucil offered an overall survival advantage compared to chlorambucil alone, significantly reducing the risk of death by 53% (HR 0.47, 95% CI 0.29–0.76, p=0.0014)2
  • 37.7% of patients receiving GAZYVA-plus-chlorambucil achieved a negative minimal residual disease (MRD) blood test result, versus 3.3% with MabThera-plus-chlorambucil.1 The CLL11 authors stated, “With longer follow-up, the higher rate of eradication of minimal residual disease that was observed with obinutuzumab as compared with rituximab may lead to an overall survival benefit in addition to the improvement in progression-free survival.”1
  • Time to next anti-leukaemic treatment was significantly longer with GAZYVA-plus-chlorambucil compared to MabThera-plus-chlorambucil (42.7 versus 32.7 months, HR 0.54, 95% CI 0.40–0.72, p<0.001).2

Key Safety Information

For full safety information, please refer to the GAZYVA Data Sheet available here.3

Infusion-related reactions (IRRs)

IRRs are the most common adverse effect seen with GAZYVA (all grades 66% with GAZYVA-plus-chlorambucil compared to 38% with MabThera-plus-chlorambucil).3

The majority of IRRs occur with the first infusion, with most patients having no IRRs during the second and subsequent administrations of GAZYVA.3

In the majority of patients, IRRs are mild to moderate and can be managed by the slowing or temporary halting the first infusion. However, severe and life-threatening IRRs requiring symptomatic treatment have also been reported.3

To help prevent IRRs, follow this advice:3

  • Split the first dose over two days (100 mg on day 1 and 900 mg on day 2)
  • Ensure adequate hydration for two days prior to the infusion
  • Pre-medicate with glucocorticoids, antihistamines and analgesics
  • Avoid anti-hypertensives for 12 hours before, during and 1 hour after the completion of infusions
  • For patients with a high tumour burden, circulating lymphocyte count >25 x 109L or renal impairment (CrCl <70 ml/min), administration of an uricostatic (e.g. allopurinol) is also recommended
  • Reassure and prepare patients for IRRs

Refer to the healthcare professional booklet here for information on how to prevent and manage IRRs in your patients.

Warnings and Precautions3

Infusion related reactions (IRRs)

  • Severe, life-threatening IRRs have been reported.
  • Follow premedication instructions and modify infusion rate as advised under Dosage & Administration (see Data Sheet).
  • Stop infusion and permanently discontinue for Grade 4 IRRs, second occurrence of Grade 3 IRR or acute life-threatening respiratory symptoms.
  • Carefully monitor patients with pre-existing cardiac or pulmonary conditions.
  • Consider withholding antihypertensive medication for 12 hours prior to, during, and the first hour after infusion.
  • Patients experiencing IR symptoms should not drive or operate machines until symptoms abate.

Hypersensitivity including anaphylaxis;

  • Stop and discontinue permanently in patients experiencing hypersensitivity (typically after previous exposure and not first infusion).

Tumour lysis syndrome

  • Patients at high risk of TLS (see Data Sheet) should receive prophylaxis with uricostatics and hydration starting 12-24 hrs prior to infusion.
  • All at risk patients should be carefully monitored during initial treatment.
  • For TLS treatment, correct electrolyte abnormalities, monitor renal function and fluid balance; administer supportive care, including dialysis as indicated.

Neutropenia

  • Severe/life-threatening neutropenia including febrile neutropenia, late onset, and prolonged neutropenia have been reported.
  • Closely monitor patients until resolution.
  • Treat concomitant infection; consider G-CSF therapy.

Thrombocytopenia

  • Severe/life-threatening thrombocytopenia including acute thrombocytopenia, and fatal haemorrhagic events have been reported during Cycle 1 infusion.
  • Closely monitor patients; perform regular laboratory tests until the event resolves.
  • Transfusion of blood products is at the discretion of the treating physician.

Cardiac conditions

  • Worsening of pre-existing cardiac conditions has been observed in patients with underlying cardiac disease.
  • These events may occur as part of an IRR and can be fatal.
  • Closely monitor patients with a history of cardiac disease.
  • Hydrate with caution.

Infections

  • Do not administer to patients with active infections and exercise caution in those with a history of recurring or chronic infections.
  • Serious bacterial, fungal, and new or reactivated viral infections can occur during and following the completion of therapy.
  • Potential HBV reactivation; screen all patients prior to treatment.
  • Do not treat patients with active disease and refer patients with positive serology to a specialist before commencing treatment.

Progressive multifocal leucoencephalopathy (PML)

  • PML has been reported in patients treated with anti-CD20 antibodies including GAZYVA.
  • Consider PML in any patient presenting with new-onset neurologic manifestations.
  • Withhold treatment during investigation and permanently discontinue if PML is confirmed.

Immunisation

  • Immunisation with live virus vaccines is not recommended until B-cell recovery.
  • Newborns, to mothers exposed to GAZYVA during pregnancy, should not receive live vaccines until B-cell levels are within normal ranges.

Use with caution in moderate renal impairment (CrCl <50ml/min) and in elderly patients (≥75 years). Patients experience more SAEs and AEs leading to death.

Pregnancy: Category C.

  • Avoid treatment during pregnancy unless potential benefit to mother outweighs potential risk to foetus.
  • Use effective contraception during treatment and for 18 months following treatment.
  • Discontinue breast-feeding during therapy and for 18 months after the last dose.

Adverse Effects: (See Data Sheet for complete list)3

  • IRRs: nausea, chills, hypotension, pyrexia, vomiting, dyspnoea, flushing, hypertension, headache, tachycardia, and diarrhoea. Respiratory and cardiac symptoms including bronchospasm, cough, larynx and throat irritation, wheezing, laryngeal oedema and atrial fibrillation.
  • Blood and lymphatic disorders: neutropenia, thrombocytopenia, leucopenia, anaemia.
  • Infections and Infestations: UTI, oral herpes, rhinitis, pharyngitis, nasopharyngitis.
  • Metabolism and nutrition disorders: Tumour lysis syndrome, hyperuricaemia.
  • Musculoskeletal and connective tissue disorders: arthralgia, back pain, musculoskeletal chest pain.
  • Investigations: decreased WBC and neutrophil count, weight increase, transient elevation in liver enzymes shortly after the first infusion.
  • Neoplasms, benign, malignant or unspecified: squamous cell carcinoma of skin.
  • Gastrointestinal disorders: constipation.
  • Skin and subcutaneous disorders: alopecia.

For information on the use of MabThera for CLL, click here or refer to the Data Sheet available here.

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

References

  1. Goede V, Fischer K, Busch R, et al. Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions N Engl J Med 2014;370(12):1101-1110.
  2. Goede V, Fischer K, Engelke A, et al. Obinutuzumab as frontline treatment of chronic lymphocytic leukemia: updated results of the CLL11 study. Leukemia 2015; 29: 1602–1604
  3. GAZYVA® (obinutuzumab) Data Sheet. Available here.

GAZYVA Patient Booklet

This booklet provides answers to questions that are commonly asked by patients who are considering treatment with GAZYVA. It is not meant to substitute any guidance, advice or help provided by their doctor, nurse or pharmacist.

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

Click the image to download the GAZYVA Patient Booklet.

GAP Booklet


Click the image to download the Infusion Guidelines Booklet

GAP Booklet