Incorporates the 2014 BCSH guidelines on diagnosis and management of multiple myeloma, plus the 2012 guidelines for supportive care in myeloma.

BCSH Guidelines advocate either immunohistochemistry on trephine to best quantify plasma cell infiltrate at diagnosis or flow cytometry – as we expect to underestimate plasma cell numbers by flow, I’ve emphasised the trephine.

“Bone marrow aspirate shows an increase in plasma cells, > 10% (see diagnostic criteria). Bone marrow trephine may show areas of plasma cell replacement when the aspirate is non-diagnostic, reflecting the focal nature of marrow involvement, at least in the early stages. The current BCSH guidelines emphasise the importance of the trephine and of immunohistochemistry when assessing the extent of myelomatous infiltrate – “Plasma cell phenotyping by flow cytometry and/or immunohistochemistry on trephine biopsy sections is recommended in all cases” (Bird et al, 2014).”

BCSH Guidelines suggest performing a panel of FISH assays for important recurrent translocations at diagnosis and suggest that conventional karyotyping should only be performed if part of a clinical trial in which the patient is a participant.

“Certain cytogenetic and molecular genetic abnormalities can predict outcome in myeloma. The following are demonstrable using FISH and confer a poor prognosis: t(4;14), t(14;16), t(14;20), del17p and +1q. Chromosome 13 deletions are not actually an independent prognostic marker but are closely associated with other high risk abnormalities such as t(4;14) so are seen in poor risk disease. The European Myeloma Network recommend FISH testing specifically for t(4;14), t(14;16) and 17p13 deletions although there is no current evidence to suggest that therapy should be altered based on cytogenetic results. The expense of these tests are often difficult to justify when other routine prognostic tools are available.

Cytogenetics may be required for some trials in myeloma but the current consensus is that conventional karyotyping is of little value”.

I have mentioned CT skeletal survey as an alternative to standard skeletal survey. However, the current BCSH guidelines still have plain radiographs rather than CT skeletal survey as the diagnostic standard.

I have not mentioned PET CT but plan to shortly. It is an appropriate means of assessing disease in non-secretory / minimally-secretory disease (although bone marrow examination would be an alternative).

Lenalidomide now gets a mention as a PHARMAC-funded option:

"Lenalidomide is approved for use as second or third line therapy in myeloma and is now funded by PHARMAC. Special authority for subsidy can be obtained for treatment of relapsed/refractory myeloma with progressive disease, either as third line treatment or as second line in patients who have experienced severe (grade 3), dose-limiting, peripheral neuropathy with bortezomib/thalidomide that precludes further treatment with either of these agents."

Sections on thromboprophylaxis, risk-stratification when selecting optimal thromboprophylaxis, and tables for dose-adjustment of lenalidomide in renal impairment and cytopenias.

Mention of the place for 2nd autologous transplants and advisability of harvesting sufficient stem cells for 2 high dose procedures in selected patients.

Section addressing question about need for biochemistry tests prior to administration of pamidronate and zolendronic acid:

In patients with existing renal impairment, on monthly pamidronate, I think we should check creatinine before every infusion and withhold if the creatinine has risen to >10% above baseline. If no pre-existing renal impairment and patient is on monthly pamidronate, I think we can afford to only check biochemistry when the patient attends their clinic appointment (usually every 2 or 3 months).

In the smaller group of patients receiving zolendronic acid regularly, the following dose adjustments are recommended by the manufacturer in the presence of renal impairment. As the risk seems to be greater with zolendronic acid, I would propose that the creatinine clearance be calculated prior to every infusion of zolendronic acid and dose-adjusted as follows:

Baseline creatinine clearance (mL/min)	Zometa recommended dose*
> 60	4.0 mg zoledronic acid
50–60	3.5 mg* zoledronic acid
40–49	3.3 mg* zoledronic acid
30–39	3.0 mg* zoledronic acid

“Prescribing IV Bisphosphonate

Pamidronate

30 mg in 250 ml normal saline over 1 hour, repeat every month.

Note: A copy of the prescription sheet for Pamidronate is available.

See the Pamidronate Data Sheets on Medsafe.

Patients with pre-existing renal impairment are thought to be particularly susceptible to bisphosphonate-induced renal damage.

The creatinine clearance should be determined before starting pamidronate infusions and the dose and rate determined according to the manufacturer’s instructions – slow infusion rate to 20 mg/hr if mild to moderate renal impairment; not recommended if creatinine clearance 30ml/min. In patients known to have renal impairment, the creatinine should be checked prior to each monthly pamidronate and the dose withheld if the creatinine has risen >10% above baseline.

The table below summarises the recommended dose reductions of bisphosphonates in cases where the benefit of calcium reduction is likely to outweigh the risk of renal damage.

Creatinine Clearance	Pamidronate	Zolendronate
30/35-60 mL/min	No dose modification. The infusion rate should not exceed 90 mg over 4 hours	No dose modification
10-30 mL/min	30 mg to be given over 2-4 hours	Not recommended
<10 mL/min	30 mg to be given over 2-4 hours	Not recommended