DARWIN EU® Multiple myeloma: patient characterisation, treatments and survival in the period 2012-2022

Study type

• Study topic:
  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Disease epidemiology

  Drug utilisation

  Effectiveness study (incl. comparative)
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Medicinal product name, other:
  Etidronate (ATC code: M05BA01), Etidronate (ATC code: L01XH03)
• Study drug International non-proprietary name (INN) or common name:
  AXICABTAGENE CILOLEUCEL

  BORTEZOMIB

  BREXUCABTAGENE AUTOLEUCEL

  CARFILZOMIB

  CISPLATIN

  CYCLOPHOSPHAMIDE

  DARATUMUMAB

  DENOSUMAB

  DEXAMETHASONE

  ELOTUZUMAB

  IDECABTAGENE VICLEUCEL

  ISATUXIMAB

  LENALIDOMIDE

  LISOCABTAGENE MARALEUCEL

  POMALIDOMIDE

  SELINEXOR

  THALIDOMIDE

  TISAGENLECLEUCEL

  VENETOCLAX

  ZOLEDRONIC ACID
• Anatomical Therapeutic Chemical (ATC) code:
  (H02AB02) dexamethasone

  dexamethasone

  (H02AB07) prednisone

  prednisone

  (L01AA01) cyclophosphamide

  cyclophosphamide

  (L01AA03) melphalan

  melphalan

  (L01AA09) bendamustine

  bendamustine

  (L01CA02) vincristine

  vincristine

  (L01CB01) etoposide

  etoposide

  (L01DB01) doxorubicin

  doxorubicin

  (L01XA01) cisplatin

  cisplatin

  (L01XC23) elotuzumab

  elotuzumab

  (L01XC24) daratumumab

  daratumumab

  (L01XC38) isatuximab

  isatuximab

  (L01XG02) carfilzomib

  carfilzomib

  (L01XG03) ixazomib

  ixazomib

  (L01XL06) brexucabtagene autoleucel

  brexucabtagene autoleucel

  (L01XL07) idecabtagene vicleucel

  idecabtagene vicleucel

  (L01XL08) lisocabtagene maraleucel

  lisocabtagene maraleucel

  (L01XX32) bortezomib

  bortezomib

  (L01XX52) venetoclax

  venetoclax

  (L01XX66) selinexor

  selinexor

  (L01XX70) axicabtagene ciloleucel

  axicabtagene ciloleucel

  (L01XX71) tisagenlecleucel

  tisagenlecleucel

  (L04AX02) thalidomide

  thalidomide

  (L04AX04) lenalidomide

  lenalidomide

  (L04AX06) pomalidomide

  pomalidomide

  (M05BA02) clodronic acid

  clodronic acid

  (M05BA03) pamidronic acid

  pamidronic acid

  (M05BA06) ibandronic acid

  ibandronic acid

  (M05BA08) zoledronic acid

  zoledronic acid

  (M05BX04) denosumab

  denosumab

  (M05BA01) etidronic acid

  etidronic acid
• Medical condition to be studied:
  Plasma cell myeloma

  Plasmacytoma
• Additional medical condition(s):
  Amyloid light chain amyloidosis due to multiple myeloma, Asymptomatic multiple myeloma, Bone marrow: myeloma cells, Extramedullary plasmacytoma, Hypogammaglobulinemia due to multiple myeloma, IgA myeloma, IgD myeloma, IgG myeloma, Indolent multiple myeloma, Kappa light chain myeloma, Lambda light chain myeloma, Light chain myeloma, Light chain nephropathy due to multiple myeloma, Multiple myeloma, Multiple myeloma in remission, Multiple solitary plasmacytomas, Myeloma-associated amyloidosis, Myeloma kidney, Neuropathy due to multiple myeloma, Non-secretory myeloma, Osteoporosis co-occurrent and due to multiple myeloma, Osteosclerotic myeloma, Plasma cell leukemia, Plasma cell leukemia in relapse, Plasma cell leukemia in remission, Primary cutaneous plasmacytoma, Relapse multiple myeloma, Smoldering myeloma, Solitary osseous myeloma

Population studied

• Short description of the study population:
  The study population included all individuals identified in the contributing databases between 01/01/2012 and 31/12/2022 with a first diagnosis of multiple myeloma. Participants with a diagnosis of cancer (any, excluding non-melanoma skin cancer) any time prior to the diagnosis of multiple myeloma were excluded.
• Age groups:
  • Children (2 to < 12 years)
  • Adolescents (12 to < 18 years)
  • Adults (18 to < 46 years)
  • Adults (46 to < 65 years)
  • Adults (65 to < 75 years)
  • Adults (75 to < 85 years)
  • Adults (85 years and over)
• Estimated number of subjects:
  20000000

Study design details

• Study design:
  Population-based cohort study.
• Main study objective:
  To characterise patients with multiple myeloma(MM) diagnosed 2012-2022. Specific objectives are to describe demographic and clinical characteristics of patients with MM at the time of diagnosis, MM treatments and MM treatment sequences and to estimate survival of incident MM cases during the study.
• Setting:
  Inpatient and outpatient setting from 6 databases in 5 European countries.
• Outcomes:
  Treatment/s initiated at index date, 1 to 30, 1 to 90 and/or 1 to 365 days post index date, and death.
• Data analysis plan:
  Large-scale patient-level characterisation will be conducted. Age and sex at time of multiple myeloma diagnosis, medical history and medication use will be described. The number and % of patients receiving each of a pre-specified list of multiple myeloma treatments and treatment combinations will also be described. Additionally, treatment patterns and sequences over time will be described. Survival will be estimated as the probability of survival from any cause of death and will be reported using Kaplan-Meier plots. This analysis will be conducted only for databases with complete information on mortality. A minimum cell count of 5 will be used when reporting results, with any smaller counts obscured.
• Summary results:
  CONCLUSION ; In this study we provided a characterisation of 30,319 patients newly diagnosed with multiple myeloma in between 2012 and 2022 across Europe. The most frequent co-morbidities at and prior to the date of diagnoses were hypertension, renal impairment, hyperlipidemia, osteoarthritis, urinary tract infection, diabetes mellitus, and obesity, while the most frequent medications were drugs for acid related disorders, agents acting on the renin-angiotensin system, lipid modifying agents, opioids and psycholeptics. ; Regarding multiple myeloma treatments, the most frequently used class of treatment in the year following diagnosis were glucocorticoids, followed by PIs, chemotherapies and IMiDs. Treatment sequences were described in CDWBordeaux, where the most common treatment sequences observed were only Melphalan, followed by Dexamethasone-Thalidomide-Bortezomib-Cyclophosphamide-Melphalan, Daratumumab, and Prednisone-Melphalan-Bortezomib. No difference in treatment was observed by sex, while IMiDs and PIs were consistently seen to be used less in older individuals. ; The observed 5-year survival estimates were 0.49 (0.42 to 0.58) in IMASIS, 0.65 (0.64 to 0.66) in NCR, and 0.69 (0.67 to 0.7) in SIDIAP. Survival estimates were higher for CDWBordeaux and EBB, with 5-year survival estimated at 0.78 (0.75 to 0.81) and 0.76 (0.67 to 0.86). Survival probabilities were consistently similar by sex, but varied substantially by age groups, with a decrease in survival observed with older age.