B-cell lymphoma vaccine (BiovaxID) for follicular non-hodgkin s lymphoma

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1 B-cell lymphoma vaccine (BiovaxID) for follicular non-hodgkin s lymphoma May 2010 This technology summary is based on information available at the time of research and a limited literature search. It is not intended to be a definitive statement on the safety, efficacy or effectiveness of the health technology covered and should not be used for commercial purposes. The National Horizon Scanning Centre Research Programme is part of the National Institute for Health Research

2 B-cell lymphoma vaccine (BiovaxID) for follicular non-hodgkin s lymphoma Target group Follicular non-hodgkin s lymphoma (FNHL) grade 1, 2, or 3a, with stage II bulky disease or stage III/IV, in first complete or unconfirmed remission achieved with chemotherapy maintenance therapy. Technology description B-cell lymphoma vaccine (BiovaxID, FNHLId1) consists of an autologous, lymphoma associated, idiotype immunoglobulin antigen conjugated to keyhole limpet haemocyanin (KLH). This vaccine is developed from the patient s malignant B-cells obtained from biopsy, fused with the heterohybridoma line and cultured. It is designed to stimulate a patient s immune system to specifically target, recognise and destroy malignant B-cells which may remain following chemotherapy while sparing normal cells. BiovaxID is administered by subcutaneous injection (SC) at 0.5mg once monthly in combination with GM-CSF 100µg/m² SC daily for four days every month, with five vaccines given over 6 months. Innovation and/or advantages BiovaxID is a new immunostimulant cancer vaccine that may be associated with a superior safety profile than existing maintenance therapy (rituximab) and offers the potential for longer disease free survival. Developer Biovest International Inc. Availability, launch or marketing dates, and licensing plans BiovaxID is a designated orphan drug in the EU and USA. It is currently in phase III clinical trials. NHS or Government priority area This topic is relevant to the NHS Cancer Plan (2000) and Cancer Reform Strategy (2007). Relevant guidance NICE technology appraisal in development. Rituximab for the maintenance treatment of follicular non-hodgkin s lymphoma following response to first line chemotherapy. Expected January NICE technology appraisal. Rituximab for the treatment of relapsed or refractory stage II or IV follicular non-hodgkin s lymphoma (review of technology appraisal guidance 2 37) NICE technology appraisal. Rituximab for the treatment of follicular lymphoma NICE technology appraisal. Rituximab for aggressive non-hodgkin s lymphoma European Society for Medical Oncology (ESMO). Newly diagnosed and relapsed follicular lymphoma: ESMO clinical recommendations for diagnosis, treatment and follow up

3 Clinical need and burden of disease NHLs are malignant tumours of the lymphoid system that usually manifest by enlargement of the lymph nodes throughout the body. The NHLs are traditionally divided into two prognostic groups: Indolent or low-grade lymphomas with a long median survival. The majority of lymphomas, including FNHL, fall into this group. They are currently incurable at advanced stages with a median survival of 8 to 10 years. Aggressive or high-grade lymphomas. These have a short natural history and a 50-60% cure rate. These are more likely to be amenable to cure. NHL is staged (stages I to IV) by how widely dispersed affected lymph nodes and extralymphatic disease are around the body. In England and Wales there were 9,431 new cases of NHL diagnosed in 2006, and 4,011 deaths registered in Follicular lymphoma, which is the most common subtype of NHL, accounts for about 25% of all NHL diagnoses i.e. approximately 2,360 new cases in Disease remissions characteristically become shorter with each successive treatment. Existing comparators and treatments Management options used in sequence include: Watching and waiting whilst the disease remains stable and the patient symptom free. Radiotherapy to affected lymph nodes. Single agent chemotherapy such as chlorambucil with or without steroids, or fludarabine or rituximab. Combination chemotherapy such as cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) with or without additional agents such as fludarabine or rituximab (R-CHOP). Radioimmunotherapy Ƴ 90 radiolabelled ibritumomab tiuxetan (Zevalin). High-dose chemotherapy with stem cell support second and subsequent line therapy. Rituximab monotherapy can be used as maintenance therapy in patients with replapsed FNHL who are in remission. Efficacy and safety Trial FNHL in first remission; phase II. FNHL; phase II. BV301, NCT ; BiovaxID or control vaccine; phase III. Biovest International. Sponsor Accentia Biopharmaceuticals, Inc. Accentia Biopharmaceuticals, Inc. Status Published. Published. Trial complete but unpublished. Source of Abstract 8, editorial Publication. Trial registry, information manufacturer. Location USA. USA. USA, Russia and Ukraine. Design Non-randomised, Non-randomised, Randomised, activecontrolled. uncontrolled. uncontrolled. Participants and schedule n=20; adults; FNHL; chemotherapy-induced first clinical complete remission. Received BiovaxID, 0.5mg n=41; adults; FNHL; chemotherapy-induced clinical remission. Received 5 doses of BiovaxID over 20 weeks. n=117; adults; FNHL; surface IgM or IgG phenotype; stage III-IV with lymph node >2cm or stage II with >5cm; 3

4 once monthly in combination with GM-CSF 100µg/m² for 4 days a mth, over 4 mths, with booster doses at 6, 9, 12, 15, 18 and 21 mths. complete remission after chemotherapy. Randomised to GM-CSF 100µg/m² for 4 days a mth, with 5 idiotype (BiovaxID) vaccinations or KLH (control) vaccinations over a 6 mth period. Follow-up Until relapse. Until relapse. 4 yrs or until relapse. Primary Disease-free survival. Overall survival and Disease-free survival. outcome progression-free survival. Secondary outcomes Key results Adverse effects (AEs) Overall survival. Safety. Molecular complete remission; molecular disease-free survival impact; immunologic response to tumour; overall survival; safety. Median disease-free survival, 96.5 mths; overall survival, 95%. None reported. Median progression-free survival, 4.4 yrs. Transient local skin reaction, arthralgia and fever. Median disease-free survival, 44.2 mths with BiovaxID vs 30.6 mths for control; 44% increase in cancer-free survival (13.6 mths). Non-specific cardiovascular, gastrointestinal, musculoskeletal, neurological AEs and pain. Estimated cost and cost impact Rituximab, 375mg/m², as maintenance therapy costs per annum a,12. Claimed or potential impact speculative Patients Reduced mortality or increased length of survival Other: Services Increased use: biopsy, administration of vaccine Decreased use Costs Increased unit cost compared to alternative New costs: additional treatment option Reduction in associated morbidity or Improved quality of life for patients and/or carers Service organisation Other: may increase time in remission Increased costs: more patients coming for treatment Savings: may delay need for treatment for relapse Quicker, earlier or more accurate diagnosis or identification of disease None identified Staff requirements None identified Increased costs: capital investment needed Other: a Person with an average body surface area of 1.7m² (assuming wastage) 4

5 References 1 National Institute for Health and Clinical Excellence. Rituximab for the maintenance treatment of follicular non-hodgkin s lymphoma following response to first-line chemotherapy. Technology appraisal in development. London: NICE; expected completion January th wave. 2 National Institute for Health and Clinical Excellence. Rituximab for the treatment of relapsed or refractory stage III or IV follicular non-hodgkin s lymphoma (review of technology appraisal guidance 37). Technology appraisal TA137. London: NICE; February Rituximab for the treatment of follicular lymphoma. Technology appraisal TA110. London: NICE; September National Institute for Health and Clinical Excellence. Rituximab for the treatment of aggressive non-hodgkin s lymphoma. Technology appraisal TA65. London: NICE; September European Society for Medical Oncology. Newly diagnosed and relapsed follicular lymphoma: ESMO clinical recommendations for diagnosis, treatment and follow up. Clinical recommendations. Annals of Oncology Cancerstats. Cancer Research UK Accessed 31 March LymphomaInfo.net 8 Santos C, Stern L, Katz L, et al. BiovaxID vaccine therapy of follicular lymphoma in first remission: Long term follow-up of a phase II trial and status of a controlled, randomized phase III trial. Blood, 2005, 106: Abstract Longo D.L. Idiotype vaccination in follicular lymphoma: Knocking on the doorway to cure. Journal of the National Cancer Institute 2006; 98: Hsu, F.J, Caspar, C.B, Czerwinski, D et al. Tumor-specific idiotype vaccines in the treatment of patients with B-cell lymphoma Long-term results of a clinical trial. Blood 1997; 89: ClinicalTrials.gov. Phase 3, randomized, double-blind, active-controlled study of FNHLId1 with local GM- CSF in patients with first complete remission. Accessed 12 April British Medical Association and Royal Pharmaceutical Society of Great Britain. British National Formulary. Number 59. BMJ Publishing Group, London. March The National Institute for Health Research National Horizon Scanning Centre Research Programme is funded by the Department of Health. The views expressed in this publication are not necessarily those of the NHS, the NIHR or the Department of Health The National Horizon Scanning Centre, Department of Public Health and Epidemiology University of Birmingham, 90 Vincent Drive, Edgbaston, Birmingham, B15 2SP, England Tel: +44 (0) Fax +44 (0)