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Multiple Myeloma -primary care review

Neoplastic proliferation of plasma cells in the bone marrow and occasionally in other organs as the liver , spleen and lymph nodes.


Rare disease which occurs predominantly in the geriatric population with a median age of diagnosis of about 70 yrs MM represents 1.8 % of all new cancer cases in the US 2nd most common haematological malignancy ( after lymphoma ) Seen more often in African Americans in comparison to European American population More common in men and extremely rare in those below 30 Generally not considered a genetic disease , although there is some evidence that genetic abnormalities in oncogenes as CMYC , NRAS and KRAS may play a role in development of plasma cell proliferation.


Malignancy of plasma cells characterized by malignant proliferation of monoclonal plasma cells in the bone marrow Plasma cell malignancies include a spectrum of conditions as
○ monoclonal gammopathy of undetermined significance○ smoldering multiple myeloma ( SMM )○ clinical multiple myeloma○ plasma cell leukaemia In multiple myeloma plasma cells make a clone of itself and these malignant plasma cells or myeloma cells accumulate in the bone marrow. The malignant cells secrete an antibody , called the M protein or M-spike or paraprotein or myeloma protein- these can be detected in blood and or urine of most patients ( it is a part of spectrum of monoclonal gammopathy ) It is now known that almost all cases of MM evolve from the MGUS precursor state Risk of progression to MM is quoted at 1 % per year Not all MGUS cases progress to MM and some may develop into Waldenström’s macroglobulinemia , primary AL amyloidosis or a lymphoproliferative disorder.


end organ damage may take several years accumulation of the monoclonal protein can cause organ or tissue damage other main effects are as follows ( main effect is on the bones )


Bone –osteolytic lesion ( hallmark of MM )
○ uncoupling of the bone remodeling process
○ activation of osteoclasts and suppression of osteoblasts resulting in bone loss
○ about 60 % of patients with MM will develop a fracture during the course of the disease
( pathological fracture ) bone pain hypercalcemia due to unopposed osteolysis


Blood -clonal , malignant plasma cells accumulate in the bone marrow anaemia can be present in > 60 % of patients on diagnosis


Renal -light chains can cause tubular obstruction and tubulo-interstitial inflammation -this can cause acute kidney injury


Spinal cord compression-due to retropulsion of pathological vertebral fractures or extramedullary soft tissue plasmocytomas


Risk factors -Age ( neoplasm of older adults ) Sex ( about 1.5 times more common in men than women ) Race ( twice more common among African Americans ) Family history ( family clusters of MM have been described )


Smouldering myeloma diagnostic features consistent with myeloma but no end organ damage or tissue injury-ie asymptomatic


Plasma cell leukaemia an aggressive subgroup of myeloma with presence of peripheral blood plasma cells-arising de-novo or from an existing myeloma


MGUS pre-malignant disorder- can progress to MM or other lymphoproliferative disorders at the rate of 1 % / year


Can present with constellation of symptoms – diagnosis can be challenging 
( often delayed ) Asymptomatic patients may be identified through incidental findings on routine testing as anaemia , hypercalcemia and evidence of kidney damage ( e.g proteinuria ) or paraproteinemia

 Presenting features are due to infiltration of malignant plasma cells into the bones or other organs ( eg myelosuppression , hepatosplenomegaly ) 

○ bone pain and pathological fractures ( vertebral crush fractures , long bone fractures )
○ anaemia○ recurrent infections ( for e.g pneumonia , pyelonephritis )
○ hypercalcemia
○ renal impairment

Paraprotein load – hyperviscosity , peripheral neuropathy or 
light chains in serum ( eg renal failure due to light chain nephropathy )
 Older adults may c/o constitutional symptoms as fatigue , weight loss , bone pain ( particularly back and neck )
 Anemia related symptoms as pallor , palpitations , worsening of heart failure , chest pain
 Hyperviscosity related symptoms as
○ paraesthesia ( peripheral neuropathy ) ○ headache ○ dyspnoea
○ nasal bleeding ○ blurred vision ○ confusion
 Symptoms related to renal impairment as oedema 
 Other presenting symptoms may include hepatomegaly , splenomegaly , lymphadenopathy and fever.


Emergency presentation -acute renal failure hypercalcemia spinal cord compression hyperviscosity hemostatica abnormalities which can cause bleeding or thrombosis


Differentials -Waldenstrom’s macroglobulinemia Lymphoma CLL Smoldering multiple myeloma Primary amyloidosis MGUS Primary bone malignancy ( sarcoma , lymphoma ) HIV / AIDS


A clinical suspicion of MM should be considered in patients aged > 50 who present with vague symptoms as fatigue , lethargy , bone pain ,weight loss or recurrent infections in whom testing shows anaemia , raised calcium levels , renal impairment with elevated ESR or plasma viscosity.


FBC Serum urea and creatinine ESR or plasma viscosity Serum calcium and albumin Immunoglobulins and serum electrophoresis Urinary Bence Jones protein XR of symptomatic areas ( may reveal pathological fractures )


Diagnostic criteria have been defined by
 International Myeloma Working group.


Management -Management will depend upon
 disease risk stratification functional status / comorbidities staging ( International staging system ) gene expression profile aim of management is to prevent end organ damage and attain disease free survival ideal management involves 2-3 drug myeloablative chemotherapy followed by autologous stem cell transplantation.


Complications -as a result of the disease itself pain due to bone disease anaemia drug induced complications nephropathy hypercalcemia increased risk infections due to the disease itself and immunosuppression peripheral neuropathy cognitive deficits in patients treated with immunomodulators increased risk of development of both secondary hematologic and solid organ cancers increased risk of thromboembolism.


Pain control -avoid NSAIDs ( renal impairment ) consider agents as gabapentin , amitriptyline for neuropathic pain.


Bone pain -bisphosphonates Denosumab

Spinal disease -refer to specialist spinal teams to consider interventions as bracing , vertebroplasty or kyphoplasty


Increased risk infection-ensure vaccination for e.g pneumococcal , influenza prophylactic medications for e,g acyclovir to prevent shingles


  1. Smith DYong KMultiple myeloma doi:10.1136/bmj.f3863
  2. Michels TC, Petersen KE. Multiple Myeloma: Diagnosis and Treatment. Am Fam Physician. 2017 Mar 15;95(6):373-383. PMID: 28318212.
  3. Albagoush SA, Azevedo AM. Multiple Myeloma. [Updated 2021 Jul 30]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from:
  4. Padala, S.A.; Barsouk, A.; Barsouk, A.; Rawla, P.; Vakiti, A.; Kolhe, R.; Kota, V.; Ajebo, G.H. Epidemiology, Staging, and Management of Multiple Myeloma. Med. Sci. 20219, 3.
  5. Medical Masterclass contributors. and John Firth. “Haematology: multiple myeloma.” Clinical medicine (London, England) vol. 19,1 (2019): 58-60. doi:10.7861/clinmedicine.19-1-58
  6. Terpos, E., Ntanasis-Stathopoulos, I., Gavriatopoulou, M. et al. Pathogenesis of bone disease in multiple myeloma: from bench to bedside. Blood Cancer Journal 8, 7 (2018).
  7. CKS NHS Multiple Myeloma


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