Daratumumab Now Reimbursed as Second-line and Beyond Combination Therapy for Adult Patients with Multiple Myeloma

The Janssen Pharmaceutical Companies of Johnson & Johnson welcomes the Taiwan National Health Insurance Administration (NHIA) decision to reimburse daratumumab as second-line or subsequent combination therapy regimens for adult patients with multiple myeloma where their disease has progressed or is not responsive to first-line therapy.¹

From April 1, 2020, daratumumab will be reimbursed in combination with lenalidomide/ dexamethasone or bortezomib/dexamethasone to treat adults with multiple myeloma with good performance (ECOG < 2) who have received at least one prior therapy containing bortezomib or lenalidomide.¹ Pre-authorization is always required: first application is for 10 infusions, followed by every 4 infusions until a total of 22 infusions are completed.¹ Daratumumab should not be combined with ixazomib, carfilzomib or pomalidomide.¹

Daratumumab is the first CD38-directed antibody approved in the world to treat multiple myeloma and the only therapy in this class in Taiwan that is approved to treat this condition.² CD38 is a surface protein that is present in high numbers on multiple myeloma cells, regardless of the stage of disease.^2,3

Dr. Yeh Shih-Peng, Attending Physician of the Division of Hematology and Oncology, China Medical University Hospital, said “Multiple myeloma is an incurable blood cancer, which means the cancer is likely to return after a period of remission. Each reoccurrence makes it harder to treat the disease, so having a new treatment option available is good news for patients.

“This government subsidy will benefit around 400 patients and will help reduce their financial burden. Many patients will be encouraged to know that there is a new treatment available that extends progression free survival, while offering good quality of life,” he said.

Recent research presented at the American Society of Hematology congress last year found that patients treated in second-line with daratumumab in combination with lenalidomide/dexamethasone or bortezomib/dexamethasone experienced significant improvements in progression free survival – 4.4 years (53.3 months) compared with 1.6 years (19.6 months) for patients treated with lenalidomide/dexamethasone alone,⁵ and 27 months versus 7.9 months for those treated with bortezomib/dexamethasone alone.⁶    

The overall safety of daratumumab in combination with lenalidomide/dexamethasone or bortezomib/dexamethasone was consistent with the known safety profiles demonstrated for daratumumab monotherapy.⁴ The most common side-effects for daratumumab compared with lenalidomide/dexamethasone alone included neutropenia (65% vs 48%), anemia (40% vs 41%), thrombocytopenia (31% vs 32%), pneumonia (25% vs 17%), and diarrhea (59% vs 38%). Similar rates of discontinuations due to treatment related side-effects were observed across treatment groups (17% vs 15%).⁴

In 2007, only 386 multiple myeloma patients were diagnosed according to the Taiwan Cancer Registry Annual Report,⁶ however 626 patients were diagnosed with multiple myeloma in 2016 – an increase of more than 60% in 10 years.⁷

Daratumumab is the only CD-38 antibody approved as combination therapy in Taiwan for the treatment of adult patients with multiple myeloma whose disease has progressed or is not responsive to first line therapy. Daratumumab was approved for the treatment of adult patients with relapsed and refractory multiple myeloma in Taiwan in 2017 and reimbursed in April 2020.¹

References:

1.     The announcement of National Insurance Administration, Ministry of Health and Welfare. https://www.nhi.gov.tw/BBS_Detail.aspx?n=73CEDFC921268679&sms=D6D5367550F18590&s=F2169683761DB1AE

2.     US Food and Drug Administration. FDA approves Darzalex for patients with previously treated multiple myeloma. Press release. November 16, 2015

https://wayback.archive-it.org/7993/20170111160754/http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm472875.htm. Accessed April 2019

3.     DARZALEX® (daratumumab) EU summary of product characteristics. Janssen-Cilag International NV, Beerse, Belgium, 2016

4.     Kaufman J et al, Four-Year Follow-up of the Phase 3 Pollux Study of Daratumumab Plus Lenalidomide and Dexamethasone (D-Rd) Versus Lenalidomide and Dexamethasone (Rd) Alone in Relapsed or Refractory Multiple Myeloma (RRMM) Blood (2019) 134 (Supplement_1): 1866. Available at https://ashpublications.org/blood/article/134/Supplement_1/1866/427677/Four-Year-Follow-up-of-the-Phase-3-Pollux-Study-of

5.     Kaufman J et al, Four-Year Follow-up of the Phase 3 Pollux Study of Daratumumab Plus Lenalidomide and Dexamethasone (D-Rd) Versus Lenalidomide and Dexamethasone (Rd) Alone in Relapsed or Refractory Multiple Myeloma (RRMM) Blood (2019) 134 (Supplement_1): 1866. Available at file:///C:/Users/tlo4/AppData/Local/Microsoft/Windows/INetCache/Content.Outlook/44SZN1FV/Kaufman%20JL%20et%20al_4-yr%20FU%20-%20POLLUX_ASH%202019_Poster%23_1866.pdf

6.     Weisel et al. Efficacy and Safety of Daratumumab, Bortezomib, and Dexamethasone (D-Vd) Versus Bortezomib and Dexamethasone (Vd) in First Relapse Patients (pts) With Multiple Myeloma (MM): Four-Year Update of CASTOR. Presented at ASH 2019.

7.     2007 Cancer Registry Report in Taiwan.  https://www.hpa.gov.tw/Pages/Detail.aspx?nodeid=269&pid=6516

8.     2016 Cancer Registry Report in Taiwan.  https://www.hpa.gov.tw/Pages/Detail.aspx?nodeid=269&pid=10227

9.     Janssen Research & Development, LLC. A Study Comparing Daratumumab, Lenalidomide, and Dexamethasone With Lenalidomide and Dexamethasone in Relapsed or Refractory Multiple Myeloma. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2018 July 24]. Available at: https://clinicaltrials.gov/ct2/show/NCT02076009?term=mmy3003&rank=1 Identifier: NCT02136134.

10.   Janssen Research & Development, LLC. Addition of Daratumumab to Combination of Bortezomib and Dexamethasone in Participants With Relapsed or Refractory Multiple Myeloma. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2018 July 24]. Available at: https://clinicaltrials.gov/ct2/show/NCT02136134?term=mmy3004&rank=1 Identifie : NCT02076009.

11.   Janssen Research & Development, LLC. A Study to Evaluate Daratumumab in Transplant Eligible Participants With Previously Untreated Multiple Myeloma (Cassiopeia). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2018 July 24]. Available at: https://clinicaltrials.gov/ct2/show/NCT02541383?term=mmy3006 Identifier: NCT02541383.

12.   Janssen Research & Development, LLC. A Study of Combination of Daratumumab and Velcade (Bortezomib) Melphalan-Prednisone (DVMP) Compared to Velcade Melphalan-Prednisone (VMP) in Participants With Previously Untreated Multiple Myeloma In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2018 July 24]. Available at: https://clinicaltrials.gov/ct2/show/NCT02195479?term=mmy3007&rank=1 Identifier: NCT02195479.

13.   Janssen Research & Development, LLC. Study Comparing Daratumumab, Lenalidomide, and Dexamethasone With Lenalidomide and Dexamethasone in Participants With Previously Untreated Multiple Myeloma. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2018 July 24]. Available at: https://clinicaltrials.gov/ct2/show/NCT02252172?term=mmy3008&rank=1 Identifier: NCT02252172.

14.   Janssen Research & Development, LLC. A Study of VELCADE (Bortezomib) Melphalan-Prednisone (VMP) Compared to Daratumumab in Combination With VMP (D-VMP), in Participants With Previously Untreated Multiple Myeloma Who Are Ineligible for High-Dose Therapy (Asia Pacific Region). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2018 July 24]. Available at: https://clinicaltrials.gov/ct2/show/NCT03217812?term=MMY3011&rank=1 Identifier: NCT03217812.

15.   European Myeloma Network. Compare Progression Free Survival Btw Daratumumab/Pomalidomide/Dexamethasone vs Pomalidomide/Dexamethasone (EMN14). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2018 July 24] Available at: https://clinicaltrials.gov/ct2/show/NCT03180736?term=MMY3013&rank=2 Identifier: NCT03180736

16.   Amgen. Study of Carfilzomib, Daratumumab and Dexamethasone for Patients With Relapsed and/or Refractory Multiple Myeloma. (CANDOR). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2018 July 24] Available at: https://clinicaltrials.gov/ct2/show/NCT03158688?term=NCT03158688&rank=1 Identifier: NCT03158688.

17.   Janssen Research & Development, LLC. A Study to Evaluate 3 Dose Schedules of Daratumumab in Participants with Smoldering Multiple Myeloma In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000-[cited 2018 March 19]. Available at: https://clinicaltrials.gov/ct2/show/NCT02316106?term=smm2001&rank=1 Identifier: NCT02316106.

18.   American Cancer Society. "What Is Multiple Myeloma?" http://www.cancer.org/cancer/multiplemyeloma/detailedguide/multiple-myeloma-what-is-multiple-myeloma Accessed May 2019.

19.   Kumar, SK et al. Leukemia. 2012 Jan; 26(1):149-57.

20.   National Cancer Institute. “NCI Dictionary of Cancer Terms: Refractory.” https://www.cancer.gov/publications/dictionaries/cancer-terms?CdrID=350245  Accessed May 2019

21.   Richardson, et al. “The Treatment of Relapsed and Refractory Multiple Myeloma.” ASH Education Book. January 1, 2007 vol. 2007 no. 1 317-323.