CMP 100: ICI MULTIPLE MYELOMA

PRECEPTORSHIP
20th May 2020

Multiple Myeloma Data in SSA

Unit 052020
Fredrick Chite Asirwa, MD
Consultant Physician. Medical Oncologist & Hematologist
Executive Director, International Cancer Institute (ICI)
Email: director@intercancer.com

Overall PI/PD-Blueprint for innovative access Program, SSA &

Multi-National Lung Cancer Control Program (MLCCP), SSA
PI/PD-Shining Tower Project, SSA.

International Cancer Institute 1

www.intercancer.com
 Learning Objectives

At the end of this educational activity, participants should be

able to:
1. To appreciate the Multiple Myeloma data in SSA vs.
Globally
2. To appreciate the epidemiology of MM in SSA
3. To learn about Multiple Myeloma outcome data in sub-
Saharan Africa (SSA)
4. To learn about Multiple Myeloma outcome data in Kenya

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International Cancer Institute 3
 Multiple Myeloma
• Multiple myeloma (MM) is the second most common hematologic
malignancy, with an estimated incidence of 30,770 new cases and
12,770 deaths in the USA in 2018 and an estimated 48,300 new cases
in Europe in 2018

• Multiple myeloma (MM) is a clonal plasma cell neoplasm,

characterized by end organ damage—renal impairment,
hypercalcemia, lytic bony lesions, and anemia.

• Due to better therapies, myeloma has changed from an untreatable

ailment to a treatable but still incurable.

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INSIGHT MM: a large, global, prospective, non-interventional, real-world study of patients with multiple myeloma (2019)
Costello et al

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 MM Cont’d
• United States National Cancer Institute SEER program
estimated a 5-year relative survival of:
– 29.3% for patients with MM who were diagnosed in 1990–1992,
– 52.4% for those diagnosed in 2008–2014.

In the UK, the estimated 5-year net survival for male and female
patients diagnosed with MM between 2011 and 2015, was 51.9% and
50.8%, respectively, compared with 22.4% and 21.9%, respectively,
for those diagnosed between 1990 and 1991.

In a Swedish population-based study, the 5-year relative survival rate

improved from 0.28 to 0.41 for patients diagnosed with MM in 1973–
1982 and 2003–2013, respectively

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 MM Cont’d
• MM is two- to threefold more common in African–Americans (AAs)
compared with European–Americans. ? Genetic Predisposition?
Ref: Linda et al (2018) Differences in genomic abnormalities among African individuals with monoclonal
gammopathies using calculated ancestry
Blood Can J

• Studies in Africa indicate MM to represent 8.2% of all blood cancers

(Alao et al., 2010).
• M>W
• X2 in Blacks then Caucasians (Waxman et al., 2010; Landgren and
Weiss, 2009).
• The median age of patients with MM is 68 years for men and 70 years
for women. Only 18% of patients are younger than 50 years, and 3%
of patients are younger than 40 years. The male-to-female ratio of MM
is approximately 3:2 (Waxman et al., 2010)

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 Cont’d
 MGUS is a predisposing factor
 The mechanism driving the increased prevalence of
t(11;14), t(14;16), and t(14;20) translocations among
individuals of African descent is unclear

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Smoldering Multiple Myeloma

27% will convert in 15 years

Roughly 2% per year

Kyle R et al. N Engl J Med 2007;356:2582-2590

 2-microglobulin

 An elevated 2-
microglobulin (≥2.5) is an
adverse prognostic factor
– IgA subtype as well

 Model using 2m ≥2.5, IgA

isotype associated to 2m
≥2.5
– Median survival >111 mos.
(0 factors) vs. 43.1 (1) vs.
17.8 mos. (2)

Facon et al., 2001.

 Genetic Abnormalities In
Myeloma
Translocations Trisomies

Deletions involving chromosomes 1, 13 , 14, 17

FISH abnormality Frequency
(%)
Trisomy (ies) without IgH abnormality 201 (42%)

IgH abnormality without trisomy (ies) 146 (30%)

IgH abnormality with Trisomy (ies) 74 (15%)

Monosomy 14 in absence of IgH translocations or 22 (4.5%)

trisomy (ies)
Other cytogenetic abnormalities 26 (5.5%)

Normal 15 (3%)
Kumar S, Blood. 2012;119(9):2100-2105
Frequency of FISH abnormalities in IFM
experience

Missing t(14:16), approximately 10% of MM

IFM= Intergroupe Francophone du Myelome; FISH= Fluorescence In Situ

Hybridization Avet-Loiseau, 2007

 Del 13 impact is dependant upon other findings
m.

13 + t(4:14) 13 + del 17p

Del 13 OS without 17p or

t(4:14)

13 only

Avet-Loiseau, 2007
All t(4:14) is a poor risk factor, but
not all are the same…

Moreau et al, Leukemia 2007

 Revised ISS staging

Palumbo et al,
JCO 2015
 Tumor Biology: Disease Aggressiveness
Myeloma Risk-Stratification

Standard-Risk Intermediate-Risk High-Risk

All others including:  t(4;14)  t(14;16) (C-MAF)
 Trisomies (FGFR3/MMSET)  t(14;20) (MAF-B)
 t(11;14) (CCND1)
 t(6;14) (CCND3)
 Del 17p

Kumar S, et al. Blood. 2012;119:2100-2105

*Presence of trisomies ameliorates high risk msmart.org
 Tumor Burden: Revised International Staging System
(RISS)

Stage ~ 5-yr OS
Stage I 80%
ISS I, and normal LDH, and No high risk FISH

Stage II 60%
Not meeting criteria for Stage I or III

Stage III 40%

ISS III and either high LDH or high risk FISH

High Risk FISH = del 17p, t(4;14) or t(14;16)

Palumbo A. J Clin Oncol 2015 In Press

Clinical Presentation

 Weakness and Fatigue

 Bone Pain
 Fractures
 Infection
 Renal failure
 Clinical Presentation

 Monoclonal (M) protein

 SPEP: 82%
 SIFE: 93%

 SPEP+SIFE+ either FLC or UPEP/UIFE: 97-98%

 Clinical Presentation

 Increased plasma cells in the bone marrow

(96%)

CRAB features
 Hypercalcemia ≥ 11 (13%)

 Renal failure, serum creatinine ≥ 2.0 (19%)

 Anemia (normochromic normocytic; 73%)

 Lytic bone lesions (67%)

M protein in Myeloma
 IgG (50%)
 IgA (20%)
 Light chain only (20%)
 Rarely IgD (2%)
 Ghana
• A retrospective review of 169 MM cases diagnosed in a
Ghanaian tertiary hospital from 2002-2016 (Acquah, 2019)
Background: Africans have an increased risk for multiple myeloma (MM) compared to other races.
Objective: This report describes the clinic-pathological features of MM patients in Ghana at diagnosis,
and the factors affecting their survival.
Methods: A retrospective review of 169 MM cases diagnosed in a Ghanaian tertiary hospital from 2002-
2016.
Results: Median age was 58 years, with 29% ≤50 years. One-third presented >12 months after onset of
symptoms, which included bone pain (96%), anaemia (67%), weight loss (55%) and fractures (44%).
Myeloma-related tissue impairment included hypercalcaemia (36%), renal impairment (33%), severe
anaemia (52%) and osteolytic lesions (76%); 51.3% of patients were diagnosed in ISS Stage III. Median
survival was 33 months; 1-year and 5-year overall survival were 51.6% and 15.5%, respectively. Neither
the age at diagnosis nor the duration of symptoms prior to diagnosis correlated with prognosis. Median
survival improved with early ISS stage, haemoglobin >8g/dL, plasmacytosis <20%, and normal creatinine
and calcium levels.
Conclusion: Early onset and late stage presentation are common at diagnosis of MM patients in Ghana,
but do not affect survival. Studies into genetic associations are recommended.

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• Nigeria
• Kenya
• South Africa
• Zambia
• Tanzania
• Uganda
• (Egypt)
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 Kenya
• Started MM program in 2011
• This presentation is on 2011-2018 data
• PI: Chite Asirwa MD
– Co-Investigators
• Dr. Teresa Lotodo-Hematopathologist
• Mercy Oduor-Pharmacovigilance PharmD Officer
• MM Team

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 No of patients

Year
Age distribution

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 Gender

Female
40%
Male
60%

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 Enrolled vs Deceased Patients
200
180
160
140
No. of Patients

120
100
80
60
40
20
0
2009 2010 2011 2012 2013 2014 2015 2016 2017 2018
Enrolled 2 3 9 21 45 60 79 110 135 178
Deceased 7 11 6 21 19 8 4

Year
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 Myeloma true burden: Limitations
• Data informing the models to estimate the burden of
myeloma are often scarce, especially in LMICs/Cancer
Registries
• Diagnostics unavailability and inaccessibility
• Drugs for treatments-unavailable in most centers
• Lack of outcome data
• Transplantations options availability
• Specialists to manage MM
• Pharmacovigilance programs lacking and inadequate
patient support

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 Open-Book Assignment
1. Review the Multiple Myeloma data from your center and write a
paragraph on the following:
– Time period (e.g. April 2019-March 2020)
– Number seen/diagnosed
– Male/Female, Age, and treatments available/given
For those in non-clinical settings/with no MM diagnostics and
care; Do literature review and write one-two paragraphs on MM
in your country (20 marks)
2. In your current centers of practice; Identify and explain the
interventions that are likely have the greatest impact in MM
outcomes. (20 marks)
(You are free to form groups and discuss and write one shared paper/group. Ensure you
include all the names of those who participated. Send your final work by Monday next
week (May 27th 2020) by 4:00pm EAT)

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 Thank you

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