Multiple Myeloma: GBD 2017

Disease Overview

Multiple myeloma (MM) is a clonal plasma cell neoplasm with substantial morbidity and mortality, characterized by end organ damage—renal impairment, hypercalcemia, lytic bony lesions, and anemia. According to Global Burden of Multiple Myeloma [Cowan et al. 2018], in 2016 there were 138 509 (95% UI, 121 000-155 480) incident cases of MM, with an age-standardized incidence rate (ASIR) of 2.1 per 100 000 persons (95% UI, 1.8-2.3). Multiple myeloma was responsible for 98 437 (95% UI, 87 383-109 815) deaths globally with an age-standardized death rate (ASDR) of 1.5 per 100 000 persons (95% UI, 1.3-1.7). Multiple myeloma was responsible for 2.1 million (95% UI, 1.9-2.3 million) DALYs at the global level in 2016, with an age-standardized rate of 30.5 (95% UI, 27.4-33.9) DALYs per 100 000 person-years. From 1990 to 2016, MM incident cases increased by 126%, and deaths increased by 94%. Among SDI quintiles, the largest increase (192%) was seen in middle SDI countries (from 7974 [95% UI, 7233-8821] in 1990 to 23 273 [95% UI, 21 136-26 947] in 2016). Of the 126% increase in incident cases at the global level, population growth contributed 40.4%, an aging world population contributed 52.9%, and increases in age-specific incidence rates contributed 32.6%. Among the regions, the largest increase in incident cases from 1990 to 2016 was seen in East Asia (China, North Korea, and Taiwan), with a rise of 262% (from 4760 [95% UI, 4271-5575] in 1990 to 17 218 [95% UI, 14 482-19 093] in 2016). The largest contributor to this increase was a rise in age-specific incidence rates (contributing 157%), followed by an aging population (contributing 85%) and population growth (contributing 20%).

With the development of better therapies, myeloma has changed from an untreatable ailment to one that is still not curable but treatable with mostly outpatient therapy. Although several new treatment options for multiple myeloma are now available, there is no cure for this disease. And almost all patient with multiple myeloma develop relapse/refractory. Relapse is an inevitable feature of multiple myeloma, resulting in a continued need for new active treatments. The combination of pomalidomide and low-dose dexamethasone is an approved and established option for the treatment of relapsed and refractory myeloma in patients who have received at least two previous therapies. A randomised, multicentre, open-label, phase 3 study [Attal et al. 2019] was taken to compare isatuximab plus pomalidomide and dexamethasone with pomalidomide and dexamethasone in patients with relapsed and refractory multiple myeloma. Result shows that the addition of isatuximab to pomalidomide and dexamethasone was associated with a significant and clinically meaningful benefit in progression-free survival in heavily treated patients with relapsed and refractory multiple myeloma with results from both the investigators and an independent response committee being consistent.

GBD 2017 Modeling Strategy

Multiple myeloma in GBD 2017

The GBD modelling strategy can be found in the GBD YLD Capstone Appendix [GBD-2017-YLD-Capstone-Appendix-1-Multiple-Myeloma].

sequelae	health states	health state lay descriptions	disability weights
Diagnosis and primary therapy phase	Cancer, diagnosis and primary therapy	has pain, nausea, fatigue, weight loss and high anxiety	0.288(0.193-0.399)
Controlled phase	Generic uncomplicated disease: worry and daily medication	medication every day and causes some worry but minimal interference with daily activities	0.049(0.031-0.072)
Metastatic phase	Cancer, metastatic	has severe pain, extreme fatigue, weight loss and high anxiety	0.451(0.307-0.600)
Terminal phase	Terminal phase, with medication	has lost a lot of weight and regularly uses strong medication to avoid constant pain.	0.540(0.377-0.687)

International Classification of Diseases (ICD) codes mapped to the Global Burden of Disease cause (multiple myeloma):

• ICD10 C88-C90.32

• ICD9 203-203.9

Cause Hierarchy

Restrictions

The following table describes any restrictions on the effects of this cause (such as being only fatal or only nonfatal), as well as restrictions on the age and sex of simulants to which different aspects of the cause model apply.

Restrictions

Restriction Type	Value	Notes
Male only	False
Female only	False
YLL only	False
YLD only	False
YLL age group start	15 to 19	GBD age group id 8
YLL age group end	95 plus	GBD age group id 235
YLD age group start	15 to 19	GBD age group id 8
YLD age group end	95 plus	GBD age group id 235

Vivarium Modeling Strategy

Scope

Todo

Add scope.

Model Assumptions and Limitations

There is no remission data for multiple myeloma. Within GBD 2017, after diagnosis/ treatment if a patient survives more than 10 years, they are considered cured for calculating disability. For simulation models, this means that if the simulation is run for more than 10 years, then excess mortality rate exists due to cancer after 10 years and the number of deaths increase. But as per GBD 2017, after 10 years, the patients do not have excess mortality rate. So, this model might over estimate deaths in that scenario.

Cause Model Diagram

State and Transition Data Tables

State Definitions

State	Definition
S	Susceptible to MM
MM	with MM
RR	with relapse/refractory

States Data

State	Measure	Value	Notes
S	prevalence	1-prevalence_c486
S	excess mortality rate	0
S	disabilty weights	0
MM	prevalence	prevalence_c486
MM	excess mortality rate	\(\frac{\text{deaths\_c486}}{\text{population} \times \text{prevalence\_c486}}\)
MM	disability weights	\(\displaystyle{\sum_{s\in \text{sequelae\_c486}}} \scriptstyle{\text{disability\_weight}_s \,\times\, \text{prevalence}_s}\)	total disability weight over all sequelae with ids s_366, s_367, s_368, s_369
MM	cause specific mortality rate	\(\frac{\text{deaths\_c486}}{\text{population}}\)
RR	prevalence
RR	excess mortality rate
RR	disability weights

Transition Data

Transition	Source	Sink	Value	Notes
i_MM	S	MM	\(\frac{\text{incidence\_rate\_c486}}{\text{1 - prevalence\_c486}}\)	Incidence rate in total population is divided by 1-prevalence_c486 to get incidence rate among the susceptible population.
i_RR	MM	RR

Data Sources

Measure	Sources	Description	Notes
prevalence_c486	como	Prevalence of cause multiple myeloma
deaths_c486	codcorrect	Deaths from multiple myeloma
population	demography	Mid-year population for given country
incidence_rate_c486	como	Incidence rate for multiple myeloma
disability_weight_s{sid}	YLD appendix	Disability weights associated with each sequelae
prevalence_s{sid}	como	Prevalence of each sequelae

Validation Criteria

Todo

Describe tests for model validation.

References

[GBD-2017-YLD-Capstone-Appendix-1-Multiple-Myeloma]

Supplement to: GBD 2017 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 2018; 392: 1789–858 (pp. 310-317)