Orlanda, Florida, USA, 6 December 2010 Janssen Pharmaceutical Companies today announced the results from data presented at the 52nd American Society for Hematology Annual Meeting, which demonstrated the efficacy, safety and impact on quality of life of VELCADE® (bortezomib) in the treatment of multiple myeloma in different settings and with different routes of administration.
The results of a study comparing subcutaneous versus intravenous administration showed that the efficacy of VELCADE administered subcutaneously is similar to intravenous administration in patients with multiple myeloma while some safety advantages were observed.1
In this large multicentre, international, randomised, phase 3 open-label trial, 222 patients from 53 centres in 10 countries globally were enrolled and randomised to receive VELCADE either subcutaneously (SC) or intravenously (IV).
The study results demonstrated that the efficacy of VELCADE in patients with relapsed multiple myeloma was similar with SC and IV administration with respect to complete and partial response rates, time to disease progression, progression-free survival, one-year survival, time to response and duration of response. The data highlight the efficacy of VELCADE irrespective of its route of administration. Median progression-free survival was 10.2 months in the SC arm compared to 8.0 months in the IV arm, and one year overall survival was 72.6 percent in the SC group and 76.7 percent in the IV arm.
Some safety advantages were also observed with SC administration. The incidence of grade ≥3 treatment emergent adverse events was 57 percent for SC vs. 70 percent for IV administration.
The incidences of the following adverse events were significantly lower in the SC compared to the IV arm: any peripheral neuropathy (PN) (38 percent SC vs. 53 percent IV), grade 3 and higher PN (6 percent SC vs. 16 percent IV), and gastrointestinal disorders (37 percent SC vs. 58 percent IV).
SC administration of VELCADE also demonstrated acceptable local tolerability. Only 6 percent of patients had at least one SC local injection site reaction reported as an adverse event, with the most common being redness. All local injection site reactions were resolved with a median time to resolution of 6 days.
"We are very encouraged by the findings from this study as subcutaneous administration of VELCADE would be a good option for multiple myeloma patients as it is easier to administer and could improve patient compliance. There are also advantages where venous access is difficult and also for those patients who are at risk of developing peripheral neuropathy," says Professor Philippe Moreau, University Hospital, Nantes, France.
VELCADE administered intravenously is effective as maintenance monotherapy
Results from the UPFRONT study were also presented at the meeting. The results showed that combination therapy with three VELCADE-based regimes (VcD: Vc-dexamethasone, VcTD: Vc-thalidomide-dexamethasone, and VcMP: Vc-melphalan-prednisone) followed by VELCADE maintenance monotherapy in previously untreated multiple myeloma patients ineligible for high-dose therapy and stem cell transplantation improved complete response and also very good partial response rates as compared to the rates with induction.2 Quality of life was also assessed, and the study showed that by the end of the treatment period, patients who received one of the three VELCADE-based regimens reported significant improvements in quality of life compared with baseline values. 3
All three VELCADE-based regimens showed substantial efficacy after eight cycles, with objective response rates of 68 percent, 78 percent and 71 percent for VcD, VcTD, and VcMP, respectively. After five cycles of VELCADE maintenance, the objective response rate increased to 71 percent, 79 percent, and 73 percent in the VcD, VcTD, and VcMP arms, respectively.
Complete response / near complete response rates increased after maintenance treatment with VELCADE in all treatment arms.
"These data are very significant given that elderly and infirm patients can further benefit from prolonged VELCADE monotherapy, achieving more robust and sustained responses over time with lesser toxicity," says Professsor Ruben Niesvizky, Centre of Excellence for Lymphoma and Myeloma, Weill Cornell Medical College, New York Presbyterian Hospital, NY.
IV VELCADE well tolerated as maintenance monotherapy
In terms of tolerability, maintenance with VELCADE monotherapy was well tolerated when administered after all three induction regimens. The rates of severe adverse events were similar at the end of the five cycles of VELCADE maintenance as they were after the eight induction cycles for all three treatment arms.
After 13 treatment cycles, the five most common grade ≥3 adverse events were peripheral neuropathy (18 percent, 28 percent, and 21 percent for VcD, VcTD, and VcMP, respectively), fatigue (10 percent, 15 percent, 8 percent), diarrhoea (11 percent, 5 percent, 10 percent), neutropenia (1 percent, 3 percent, 21 percent), and pneumonia (11 percent, 6 percent, 6 percent). Study drug discontinuation due to adverse events was highest in the VcTD arm (41 percent, vs. 29 percent with VcD and 35 percent with VcMP).
About Multiple Myeloma
Multiple myeloma, a cancer of the blood, is the second most common haematological malignancy; it accounts for 1 percent of all cancers.4 Estimates by the European Network of Cancer Registries suggest there are 21,420 new cases of multiple myeloma in Europe each year and around 15,000 deaths from this illness. It is estimated that 60,000 people in Europe are currently living with multiple myeloma.4 Traditionally, multiple myeloma was associated with a poor prognosis, with a median survival of 3-5 years from diagnosis.
The focus of treatment in multiple myeloma is generally not curative; instead the primary goal is to reduce symptoms and improve quality of life. The choice of treatment is influenced by the age and general health of the patient, the number and types of previous treatments and the complications of the disease.5
Notes to editors
About VELCADE (bortezomib)
Velcade is co-developed by Millennium: The Takeda Oncology Company and Ortho Biotech Oncology Research & Development, a unit of Johnson & Johnson Pharmaceutical Research & Development, L.L.C. Millennium: The Takeda Oncology Company is responsible for commercialization of VELCADE in the U.S., Janssen-Cilag is responsible for commercialization in Europe and the rest of the world. Takeda Pharmaceutical Company Limited and Janssen Pharmaceutical K.K. entered into a co-promote agreement in May 2010 for VELCADE in Japan. VELCADE is approved in more than 90 countries and has been used to treat more than 160,000 patients worldwide.
Janssen Pharmaceutical Companies of Johnson & Johnson are dedicated to addressing and solving the most important unmet medical needs of our time, including oncology (e.g., multiple myeloma and prostate cancer), immunology (e.g., psoriasis), neuroscience (e.g., schizophrenia, dementia and pain), infectious disease (e.g., HIV/AIDS, Hepatitis C and tuberculosis), and cardiovascular and metabolic diseases (e.g., diabetes).
Driven by our commitment to patients, we develop sustainable, integrated healthcare solutions by working side-by-side with healthcare stakeholders, based on partnerships of trust and transparency.
More information can be found at www.janssen-emea.com
1 Moreau P et al. A Phase 3 Prospective Randomized International Study (MMY-3021) Comparing Subcutaneous and Intravenous Administration of Bortezomib In Patients with Relapsed Multiple Myeloma. Abstract presented at American Society of Hematology Annual Meeting 2010.
2 Niesvizky R et al. Phase 3b UPFRONT Study: Safety and Efficacy of Weekly Bortezomib Maintenance Therapy After Bortezomib-Based Induction Regimens in Elderly, Newly Diagnosed Multiple Myeloma Patients. Abstract presented at American Society of Hematology Annual Meeting 2010.
3 Niesvizky R et al. Phase 3b Patient-Reported Quality of Life in Elderly, Newly Diagnosed Multiple Myeloma Patients Treated with Bortezomib-Based Regimens: Results from the Phase 3b UPFRONT Study. Abstract presented at American Society of Hematology Annual Meeting 2010.
4 European Network of Myeloma Patient Groups http://www.myeloma-euronet.org/en/multiple-myeloma/faq.php
5 Smith A et al. Guidelines on the diagnosis and management of multiple myeloma. British Journal of Haematology 2005; 132: 410-451. Available at http://www.guideline.gov/content.aspx?id=9555 accessed November 2010