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Myeloma: Symptoms to diagnosis
Can we do better?
[Hospital name]
[Date]
What is myeloma?
ā€¢ Cancer of plasma cells Leads to:
ā€¢ Bone infiltration
- fractures (especially vertebral wedge fractures), hypercalcaemia
- pain
ā€¢ Renal damage
ā€¢ Anaemia
ā€¢ Immunosuppression
- infections
Novel therapies have dramatically improved survival in the last 15 years*
ā€¢ Median overall survival improved from ~2 ļƒ  5 years
ā€¢ Younger patients 7+ years
~5,700 cases per year in the UK
Median age: 72
* CRUK Myeloma Statistics: http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/myeloma
How does myeloma present?
Myeloma is the cancer with the longest pathway to diagnosis in the UK
ā€¢ Median time to diagnosis: 163 days*
ā€¢ ~1/3 present via emergency route
Does it matter?
ā€¢ Long time to diagnosis ļƒ  end organ damage ā€“ may be irreversible
(kyphosis, dialysis, fatal infection)
ā€¢ Survival at 12 months: 62% emergency admission vs 88%ā€  GP
ā€¢ Patient frustration & loss of trust in healthcare staff
Why?
* Howell DA et al. BMC Hematol. 2013;13(1):9
ā€  Public Health England ā€œRoutes to Diagnosis 2006-2016ā€
Presenting symptoms are non-specific
The commonest myeloma symptoms are vague:
ā€¢ Back pain is common in non-myeloma population
ā€¢ Chest, abdominal, limb pain etc (not necessarily
ā€˜bone painā€™)
ā€¢ Systemic symptoms ā€“ generally unwell
THINK MYELOMA: In any patient with persistent unexplained pain +/- generally unwell or
anaemia of unknown cause ļƒ  perform a myeloma screen
Data from TEAMM trial: Commonest presenting symptoms from 765 patients
Time from first symptom to seeing a
haematologist
Median
time
(Days)
Intra-hospital
delay
(Median IQR)
51% referred direct to haematology by GP 59 N/A
29% via acute services* (by GP or self referral) 59 9d (2-30)
21% via other non haematology speciality
e.g. Orthopaedics, Gastroenterology, Respiratory,
Renal
120 30d (9-60)
Patients presenting via non-haematology or non-acute services experience long diagnostic delays
(median 120 days)
TEAMM trial data. True diagnostic intervals will be greater because 1. patient recall of symptom duration is often underestimated, 2. does not
account for time from 1st haematology appointment to histological confirmation
* Acute services: A&E or Acute Assessment Unit
Myeloma screening tests
ā€¢ FBC, ESR, creatinine, calcium
ā€¢ Immunoglobulins, protein electrophoresis AND urinary Bence Jones protein or serum free light chains (sFLC)
ā€¢ Imaging*: skeletal survey is too insensitive ļƒ  whole body CT, MRI, PET-CT
Interpreting serum free light chains:
ā€¢ Normally kappa and lambda light chains are excreted
in similar amounts and the K:L ratio is close to one
ā€¢ In inflammation and renal impairment, absolute levels
K and L are higher but K:L ratio remains close to one
98% of myeloma cases have a K:L ratio > 7.0 or < 0.08 and/or a paraprotein >10g/l (caveat - will
not detect non-secretory myeloma: rare <1% cases)
* NICE guideline [NG35] February 2016
Monoclonal gammopathy of undetermined
significance (MGUS)
ā€¢ Pre-malignant monoclonal plasma cell disorder
ā€¢ Myeloma is always preceded by MGUS
ā€¢ MGUS is common and incidence rises with age: age >50, incidence 3% (Caucasian heritage), 5-8%
(African heritage)
ā€¢ Not all patients with a paraprotein or abnormal FCL K:L ratio have myeloma ā€“ the majority do not
Risk stratification for MGUS (score 1 for each
factor*)
ā€¢ Level of paraprotein > 15g/L
ā€¢ Non-IgG vs IgG (score 1 for non-IgG)
ā€¢ Abnormal FLC ratio
Risk of transformation to
myeloma and follow up
requirements (or not) are
determined by these criteria
*Rajkumar SV et al, Blood. 2005;106(3):812-7
Local pathways or
protocols

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Myeloma-UK-Grand-Rounds-Slide-Set-2020.pptx

  • 1. Myeloma: Symptoms to diagnosis Can we do better? [Hospital name] [Date]
  • 2. What is myeloma? ā€¢ Cancer of plasma cells Leads to: ā€¢ Bone infiltration - fractures (especially vertebral wedge fractures), hypercalcaemia - pain ā€¢ Renal damage ā€¢ Anaemia ā€¢ Immunosuppression - infections Novel therapies have dramatically improved survival in the last 15 years* ā€¢ Median overall survival improved from ~2 ļƒ  5 years ā€¢ Younger patients 7+ years ~5,700 cases per year in the UK Median age: 72 * CRUK Myeloma Statistics: http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/myeloma
  • 3. How does myeloma present? Myeloma is the cancer with the longest pathway to diagnosis in the UK ā€¢ Median time to diagnosis: 163 days* ā€¢ ~1/3 present via emergency route Does it matter? ā€¢ Long time to diagnosis ļƒ  end organ damage ā€“ may be irreversible (kyphosis, dialysis, fatal infection) ā€¢ Survival at 12 months: 62% emergency admission vs 88%ā€  GP ā€¢ Patient frustration & loss of trust in healthcare staff Why? * Howell DA et al. BMC Hematol. 2013;13(1):9 ā€  Public Health England ā€œRoutes to Diagnosis 2006-2016ā€
  • 4. Presenting symptoms are non-specific The commonest myeloma symptoms are vague: ā€¢ Back pain is common in non-myeloma population ā€¢ Chest, abdominal, limb pain etc (not necessarily ā€˜bone painā€™) ā€¢ Systemic symptoms ā€“ generally unwell THINK MYELOMA: In any patient with persistent unexplained pain +/- generally unwell or anaemia of unknown cause ļƒ  perform a myeloma screen Data from TEAMM trial: Commonest presenting symptoms from 765 patients
  • 5. Time from first symptom to seeing a haematologist Median time (Days) Intra-hospital delay (Median IQR) 51% referred direct to haematology by GP 59 N/A 29% via acute services* (by GP or self referral) 59 9d (2-30) 21% via other non haematology speciality e.g. Orthopaedics, Gastroenterology, Respiratory, Renal 120 30d (9-60) Patients presenting via non-haematology or non-acute services experience long diagnostic delays (median 120 days) TEAMM trial data. True diagnostic intervals will be greater because 1. patient recall of symptom duration is often underestimated, 2. does not account for time from 1st haematology appointment to histological confirmation * Acute services: A&E or Acute Assessment Unit
  • 6. Myeloma screening tests ā€¢ FBC, ESR, creatinine, calcium ā€¢ Immunoglobulins, protein electrophoresis AND urinary Bence Jones protein or serum free light chains (sFLC) ā€¢ Imaging*: skeletal survey is too insensitive ļƒ  whole body CT, MRI, PET-CT Interpreting serum free light chains: ā€¢ Normally kappa and lambda light chains are excreted in similar amounts and the K:L ratio is close to one ā€¢ In inflammation and renal impairment, absolute levels K and L are higher but K:L ratio remains close to one 98% of myeloma cases have a K:L ratio > 7.0 or < 0.08 and/or a paraprotein >10g/l (caveat - will not detect non-secretory myeloma: rare <1% cases) * NICE guideline [NG35] February 2016
  • 7. Monoclonal gammopathy of undetermined significance (MGUS) ā€¢ Pre-malignant monoclonal plasma cell disorder ā€¢ Myeloma is always preceded by MGUS ā€¢ MGUS is common and incidence rises with age: age >50, incidence 3% (Caucasian heritage), 5-8% (African heritage) ā€¢ Not all patients with a paraprotein or abnormal FCL K:L ratio have myeloma ā€“ the majority do not Risk stratification for MGUS (score 1 for each factor*) ā€¢ Level of paraprotein > 15g/L ā€¢ Non-IgG vs IgG (score 1 for non-IgG) ā€¢ Abnormal FLC ratio Risk of transformation to myeloma and follow up requirements (or not) are determined by these criteria *Rajkumar SV et al, Blood. 2005;106(3):812-7