Injectable MabThera® (Rituximab) Cuts Administration Time From Approximately Two Hours To About Five Minutes Without Compromising Efficacy
Data from the Phase III SABRINA trial presented at the annual meeting of the American Society of Hematology (ASH) in Atlanta (BO22334) could mean that patients living with a form of blood cancer in the UK may soon be able to receive their treatment more quickly. A new subcutaneous (SC) injection of MabThera, used for the treatment and maintenance of non-Hodgkin lymphoma (NHL), ca n be administered in approximately five minutes instead of via intravenous (IV) infusion, which usually takes over two hours.1,2
The SABRINA trial compared the MabThera SC formulation with MabThera IV in patients with previously untreated follicular lymphoma, a type of NHL. The trial met its final end point, demonstrating non-inferiority of MabThera serum concentration and also comparable efficacy for SC.1
This is good news for eligible patients as SC administration enables the delivery of MabThera in approximately five minutes versus over two hours without compromising efficacy and safety, 1,2 saving patient time in hospital receiving their treatment. It could also benefit the NHS by freeing up capacity in chemotherapy suites.
The results showed that the objective response rate (the percentage of patients whose cancer shrinks by over 50% or disappears) was 90.5% (95% CI: 80.4, 96.4) in the SC arm and 84.4% (95% CI: 73.1, 92.2) in the IV arm. Complete response (CR/CRu) rates were 46.0% (29/63 pts, 95% CI: 33.4, 59.1) for the SC arm and 29.7% (19/64 pts, 95% CI: 18.9, 42.4) for the IV arm. Stable and progressive disease rates were similar in each arm. 1
Based on this data, Roche has applied for an updated licence with the European Medicines Authority to allow eligible NHL patients in the UK to receive MabThera subcutaneously.
Dr Andrew Davies, Consultant in Medical Oncology at the University of Southampton, commented that “This is a new formulation of a drug we are very familiar with and have been using for many years. The SABRINA study demonstrates that rituximab subcutaneous injection is equivalent to rituximab IV and has a comparable safety profile. In the near future patients will be able to benefit from shorter, more convenient and potentially less complicated hospital visits. The greatly reduced administration time is not only a big plus for NHL patients, but also has the potential to ease the capacity burden in busy chemotherapy day units and allow more patients to be treated. In Southampton, we have observed a high degree of patient preference and satisfaction with this new formulation of rituximab.”
After a median follow-up of approximately nine months, the overall safety profile for MabThera SC was as would be expected for IV administration, with no new or unexpected adverse events. Adverse events include neutropenia, pruritus, chills, injection site erythema and vomiting. 1
Treatment involving MabThera is the standard of care in its licenced indications of follicular lymphoma and diffuse large B-cell non-Hodgkin’s lymphoma. 3,4,5
MabThera SC represents a significant advance in the way that NHL cancer treatment is delivered. Through its combination with a recombinant human enzyme called hyaluronidase, penetrability of the layer of tissue under the skin is temporarily increased, facilitating injection and absorption of MabThera into the body. In addition to reducing the time that a patient is required to spend receiving their treatment in hospital, the ready to use formulation may also reduce pharmacy time compared to IV, as the preparation is less complex, compared to intravenous doses of MabThera. MabThera is currently licensed in an IV formulation only.
About non-Hodgkins Lymphoma (NHL)
Non-Hodkgin lymphoma describes a set of related cancers of the lymphatic system. NHLs can be fast-growing (high-grade or aggressive), including diffuse large B-cell lymphoma, or slow-growing (low-grade or indolent), such as follicular lymphoma. Over 12,200 people are diagnosed with NHL each year in the UK. It is more common in the over-55s and it is one of the most common cancers in people aged 75 and over. 6
About MabTheraâ (rituximab)
MabThera is an antibody therapy used to treat NHL. It binds to a particular protein – the CD20 antigen – on the surface of normal and malignant B-cells and recruits the body’s natural defenses to attack and kill the marked B-cells. Unlike chemotherapy, MabThera kills only B-cells. 5,7 As MabThera is an antibody therapy, it is more discriminate than chemotherapy, and therefore has a different safety profile and fewer of the unpleasant side effects typically associated with chemotherapy e.g. vomiting, hair loss and mouth ulcers.
In the UK, MabThera is indicated in oncology for the treatment of: 5
- Non-Hodgkin’s lymphoma (NHL)
- the treatment of previously untreated patients with stage III-IV follicular lymphoma in combination with chemotherapy;
- maintenance therapy is indicated for the treatment of follicular lymphoma patients responding to induction therapy;
- treatment of patients with stage III-IV follicular lymphoma who are chemoresistant or are in their second or subsequent relapse after chemotherapy;
- treatment of patients with CD20 positive diffuse large B cell non-Hodgkin’s lymphoma in combination with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) chemotherapy.
- Chronic lymphocytic leukaemia (CLL)
- in combination with chemotherapy for the treatment of patients with previously untreated and relapsed/refractory chronic lymphocytic leukaemia.
A summary of product characteristics for MabThera is available on the EMA website: http://www.ema.europa.eu
About the SABRINA study
The Phase III SABRINA Study was designed to demonstrate the pharmacokinetics (PK), safety and overall response rate (ORR) achieved with subcutaneous (SC) administration of MabThera (rituximab) in combination with chemotherapy, in comparison with intravenous (IV) administration in patients with follicular lymphoma (FL) in the first-line setting.1 The trial met its primary endpoint of demonstrating non-inferior MabThera serum concentration after SC injection compared with MabThera IV infusion. Based on this data, Roche has made a submission for an updated licence for MabThera with the European Medicines Agency to allow all eligible NHL patients to receive MabThera subcutaneously.
About subcutaneous delivery
MabThera SC uses Enhanze™ Technology, developed by Halozyme Therapeutics, Inc. which enables the injection of large volumes of a medication under the skin (subcutaneous). It works by reversibly breaking down a gel-like substance (hyaluronan) that forms part of the framework of the tissues under the skin.
1) Davies. A et al. Pharmacokinetics (PK), Safety and Overall Response Rate (ORR) Achieved with Subcutaneous (SC) Administration of Rituximab in Combination with Chemotherapy were Comparable to Those Ahieved with Intravenous (IV) Administration in Patients (pts) with Follicular Lymphoma (FL) in the First-Line Setting: Sttagge 1 Results of the Phase III SABRINA Study (BO22334). Presented at the American Society of Hematolgy Annual Meeting 2012 Abstract # BO22334
2) Roche data on file RXUKDONF00147
3) Dreyling. M. On behalf of the ESMO Guidelines Working Group. Newly diagnosed and relapsed follicular lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol (2011) 22 (suppl 6): vi59-vi63.
4) British Committee for Standards in Haematology. Guidelines on the investigation and management of follicular lymphoma. September 2011.
5) MabThera (rituximab) Summary of Product Characteristics. Last accessed 14.11.12
6) Lymphoma Association. Information and support: frequently asked questions. Last accessed 14.11.12
7) Macmillan Cancer Support. Rituximab (MabThera®) Last accessed 14.11.12