National Institute for Health and Care Excellence Backs Darzalex®▼ (daratumumab) in Combination with Velcade® (bortezomib), Thalidomide and Dexamethasone (DVTd) for Patients with Newly Diagnosed Multiple Myeloma

National Institute for Health and Care Excellence Backs Darzalex^®▼ (daratumumab) in Combination with Velcade^® (bortezomib), Thalidomide and Dexamethasone (DVTd) for Patients with Newly Diagnosed Multiple Myeloma

High Wycombe, 22^nd December 2021 – The Janssen Pharmaceutical Companies of Johnson & Johnson welcomes the decision from the National Institute for Health and Care Excellence (NICE) recommending the use of Darzalex^®▼ (daratumumab) in combination with Velcade^® (bortezomib), thalidomide and dexamethasone (DVTd) as induction and consolidation treatment for untreated multiple myeloma in adults, when an autologous stem cell transplant (ASCT) is suitable.

[1] This positive Final Appraisal Document (FAD) means eligible patients in England and Wales will be able to access DVTd on the NHS, in line with the rest of the UK.[2]^,[3]

“Multiple myeloma is a relapsing and remitting cancer, and while existing therapies can control it, these patients are in need of effective and well-tolerated treatment options that are given as early as possible in the treatment pathway to elicit a deep response and improve outcomes,” said Dr Karthik Ramasamy, Consultant Haematologist at Oxford University Hospitals NHS Foundation Trust and Lead Clinician for Myeloma for the Thames Valley Cancer Network.* “A front-line treatment option such as daratumumab in combination with VTd will give clinicians an effective regimen to produce deeper and longer remissions for newly diagnosed myeloma patients compared to VTd alone.”

Currently, around 24,000 people are living with multiple myeloma in the UK.[4] The decision to recommend DVTd as a front-line treatment has the potential to offer eligible NHS patients longer periods of remission and improved progression-free survival versus bortezomib, thalidomide and dexamethasone (VTd) alone, while possibly delaying complications associated with multiple myeloma – an option NICE says will be welcomed by this group of people.¹

“We are delighted that people with multiple myeloma in England and Wales will now be able to access DVTd on the NHS,” said Amanda Cunnington, Director of Health Economics, Market Access, Reimbursement and Health Affairs, Janssen-Cilag Limited “Today’s decision means access will now be equal across the UK and we’re proud to have worked collaboratively with stakeholders to achieve this outcome. Importantly, our work in multiple myeloma doesn’t stop here, and we remain committed to furthering advances in science and evolving innovation in blood cancers.”

The NICE recommendation is based on data from the Phase 3 CASSIOPEIA study (Part 1) with a median follow-up of 18.8 months which compared DVTd to standard of care (bortezomib, thalidomide and dexamethasone (VTd) alone) as induction and consolidation therapy in newly diagnosed multiple myeloma patients eligible for ASCT.[5]^,[6] The primary endpoint was the proportion of patients who achieved a stringent complete response (sCR) after consolidation.⁶** The secondary endpoints included overall survival, progression-free survival (PFS), and the proportion of patients without minimal residual disease (MRD).⁶ After consolidation, the sCR rate in the DVTd arm was 29 percent compared to VTd alone which was 20 percent (Odds Ratio [OR] = 1.60; 95 percent confidence interval [CI], 1.21-2.12; P=0.0010).⁶ PFS at a median follow-up of 18.8 months was improved in the DVTd group compared to VTd alone (Hazard Ratio [HR] = 0.47; 95 percent CI, 0.33-0.67; P<0.0001), and median PFS was not reached in either arm.⁶ The rate of 18-month PFS was 93 percent for DVTd compared to 85 percent for VTd alone.⁶

The most common (≥10 percent) Grade 3/4 treatment-emergent adverse events (TEAEs) for DVTd and VTd, respectively, were neutropenia (28 percent vs. 15 percent), lymphopenia (17 percent vs. 10 percent), stomatitis (13 percent vs. 16 percent) and thrombocytopenia (11 percent vs. 7 percent).⁶ Infusion-related reactions (IRRs) of any grade occurred in 35 percent of patients in the DVTd arm (IRR figures were not recorded in the VTd arm).⁶ Infections were reported in 65 percent of patients in the DVTd arm and 57 percent of patients in the VTd arm.⁶ 7 percent of patients in the DVTd arm discontinued treatment due to an adverse event, compared to 8 percent in the VTd arm.⁶

*Dr Karthik Ramasamy has received consultancy honoraria from Janssen. Dr Ramasamy has not been compensated for any media work.

**Stringent complete response is a more rigorous response category developed by the International Myeloma Working Group to eliminate ambiguities in the response assessment and make cross-trial comparisons of efficacy simpler.[7] It differs to complete response as it includes an additional criterion for the normalisation of the kappa and lambda serum free light chain ratio plus the absence of clonal plasma cells in bone marrow by immunohistochemistry or immunofluorescence with a sensitivity of 10^-3.[8]

[1] National Institute for Health and Care Excellence. Final Appraisal Document. Daratumumab in combination for untreated multiple myeloma when stem cell transplant is suitable.

[2] Scottish Medicines Consortium. Daratumumab (Darzalex) in combination with bortezomib, thalidomide and dexamethasone for the treatment of adult patients with newly diagnosed multiple myeloma who are eligible for autologous stem cell transplant (SMC2302). Available at https://www.scottishmedicines.org.uk/medicines-advice/daratumumab-darzalex-full-smc2302. Last accessed December 2021.

[3] Health & Social Care Northern Ireland. Daratumumab (Darzalex^®) is accepted for use in combination with bortezomib, thalidomide and dexamethasone, for the treatment of adult patients with newly diagnosed multiple myeloma who are eligible for autologous stem cell transplant. Available at https://niformulary.hscni.net/managed-entry/managed-entry-decisions. Last accessed December 2021.

[4] Myeloma UK. What is myeloma? Available at https://www.myeloma.org.uk/understanding-myeloma/what-is-myeloma. Last accessed December 2021.

[5] ClinicalTrials.gov. A study to evaluate daratumumab in transplant eligible participants with previously untreated multiple myeloma (Cassiopeia). NCT02541383. Available at

https://clinicaltrials.gov/ct2/show/NCT02541383. Last accessed December 2021.

[6] Moreau P, Attal M, Hulin C, et al. Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomised, open-label, phase 3 study. Lancet. 2019;394:29-38.

[7] Kapoor P et al. Importance of Achieving Stringent Complete Response After Autologous Stem-Cell Transplantation in Multiple Myeloma. Journal of Clinical Oncology. 2013;31:36,4529-4535.

[8] Cedena MT, Martin-Clavero E, Wong S, et al. The clinical significance of stringent complete response in multiple myeloma is surpassed by minimal residual disease measurements. PLoS One. 2020;15(8):e0237155.

[9] van de Donk NWCJ, Usmani SZ. CD38 Antibodies in Multiple Myeloma: Mechanisms of Action and Modes of Resistance. Front Immunol. 2018;9:2134.

[10] DARZALEX 1,800mg solution for injection. Summary of Product Characteristics. Available at https://www.medicines.org.uk/emc/product/11488/smpc. Last accessed December 2021.

[11] DARZALEX 20mg/mL concentrate for solution for infusion. Summary of Product Characteristics. Available at https://www.medicines.org.uk/emc/product/7250/smpc. Last accessed December 2021.

[12] Cancer Research UK. Myeloma statistics. Available at https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/myeloma. Last accessed December 2021.

[13] Myeloma UK. Symptoms & complications. Available at https://www.myeloma.org.uk/understanding-myeloma/symptoms-and-complications. Last accessed December 2021.