Myeloma: Symptoms to diagnosis Can we do better? [Hospital name] [Date]

What is myeloma? Leads to: Cancer of plasma cells Bone infiltration ~5,700 cases per year in the UK Median age: 72 What is myeloma? Cancer of plasma cells Leads to: Bone infiltration - fractures (especially vertebral wedge fractures), hypercalcaemia - pain Renal damage Anaemia Immunosuppression - infections Novel therapies have dramatically improved survival in the last 15 years* Median overall survival improved from ~2  5 years Younger patients 7+ years * 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 Median time to diagnosis: 163 days* ~1/3 present via emergency route Does it matter? Long time to diagnosis  end organ damage – may be irreversible (kyphosis, dialysis, fatal infection) Survival at 12 months: 61% emergency admission vs 87%† GP Patient frustration & loss of trust in healthcare staff Why? * Howell DA et al. BMC Hematol. 2013;13(1):9 † Public Health England “Routes to Diagnosis 2006-2016”

Presenting symptoms are non-specific The commonest myeloma symptoms are vague: Back pain is common in non-myeloma population Chest, abdominal, limb pain etc (not necessarily ‘bone pain’) Systemic symptoms – generally unwell THINK MYELOMA: In any patient with persistent unexplained pain +/- generally unwell of anaemia of unknown cause  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) 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 FBC, ESR, creatinine, calcium Immunoglobulins, protein electrophoresis AND urinary Bence jones protein or serum free light chains (sFLC) Imaging*: skeletal survey is too insensitive  whole body CT, MRI, PET-CT Interpreting serum free light chains: Normally kappa and lambda light chains are excreted in similar amounts and the K:L ratio is close to one 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) Pre-malignant monoclonal plasma cell disorder Myeloma is always preceded by MGUS MGUS is common and incidence rises with age: age >50, incidence 3% (Caucasian origin), 5-8% (African origin) Not all patients with a paraprotein or abnormal FCL K:L ratio have myeloma – the majority do not Risk stratification for MGUS (score 1 for each factor*) Level of paraprotein > 15g/L Non-IgG vs IgG (score 1 for non-IgG) 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