ROYAL FREE & UNIVERSITY COLLEGE MEDICAL SCHOOL

NATIONAL AMYLOIDOSIS CENTRE

Prof PN Hawkins PhD FRCP FRCPath Clinical Director

020 7433 2815 (PA 2816) p.hawkins@medsch.ucl.ac.uk

Prof MB Pepys FRS, Head, Dept of Medicine

020 7433 2802 m.pepys@medsch.ucl.ac.uk

Dr JD Gillmore MD PhD MRCP, Senior Lecturer

020 7433 2726 j.gillmore@medsch.ucl.ac.uk

Dr HJ Lachmann MD MRCP, Senior Lecturer

020 7433 2804 h.lachmann@medsch.ucl.ac.uk

Dr AD Wechalekar MD MRCP MRCPath, Senior Lecturer

020 7433 2758 a.wechalekar@medsch.ucl.ac.uk

General Enquiries: 020 7433 2725

Ramon Lamarca (Unit Secretary) 020 7433 2811

ORAL MELPHALAN AND DEXAMETHASONE (MEL-DEX) REGIMEN

Stem cell harvesting with G-CSF alone (or with cyclophosphamide (1-2g/m2) + G-CSF in case of failure with
G-CSF alone) should be considered in all patients aged 70 yrs who may be potential autologous stem cell
transplant candidates prior to administration of oral melphalan and dexamethasone.

Mel-Dex regimen:

Day 1-4:

Oral melphalan 0.22 mg/kg daily

Day 1-4 and 15-18

Dexamethasone 40mg daily p.o if tolerated

If tolerated, the cycle is repeated every 28 days continuing to maximal response with a minimum of 3 cycles.

All patients should receive co-trimoxazole, antifungal and antiviral prophylaxis.

Attenuated Mel-Dex regimen:

Patients who are not fit to receive full dose Mel-Dex (e.g. elderly, ECOG performance status 3-4, severe fluid
overload or renal failure) or who do not tolerate full dose Mel-Dex should be given a dose attenuated version as
follows:

Day 1-4:

Oral melphalan 0.22 mg/kg daily

Day 1-4 and 15-18

Dexamethasone 20mg daily p.o.; for patients with poor tolerance and no
improvement after optimisation of diuretic doses then dexamethasone can be
dose reduced to 10mg or less for further cycles.

If tolerated, the cycle is repeated every 28 days continuing to maximal response with a minimum of 3 cycles.

Prophylaxis with co-trimoxazole, antifungal and antiviral prophylaxis should be considered.

Suggested dose modification of Mel-Dex:

a)
Dexamethasone Toxicity
Patients with AL amyloidosis are prone to dexamethasone toxicity and will require careful monitoring. The main
toxicity in such patients is likely to be fluid overload, in which case diuretic therapy should be optimized, if
necessary by addition of spironolactone. Patients often need frequent diuretic adjustments. Albumin
National Amyloidosis Centre, Royal Free & University College Medical School, Rowland Hill Street, London NW3 2PF, UK
Fax: +44 (0)20 7433 2817 www.ucl.ac.uk/medicine/nac

infusions can help to optimize fluid management in hyopalbuniaemic patients. If the response to additional
diuretic therapy is inadequate, step-wise dexamethasone dose reduction by 6 mg but keeping to the schedule
should be the next therapeutic intervention. Omission of one of the 4-day pulses of dexamethasone in a 4 week
cycle would be the next step if a 4-day pulse of 8 mg daily is not tolerated. Switching to an alternative
corticosteroid, e.g. methylprednisolone, is unlikely be of major benefit as the mineralocorticoid action is greater
for most other corticosteroids than for dexamethasone at comparable doses.
b)
Adjustments for neutropenia and/or thrombocytopenia
Myelosuppression is not a common feature of AL amyloidosis and is likely to be drug related in this group of
patients. If cytopenias occur in the course of treatment and are considered to be chemotherapy-induced,
9
modification of the regimen may be indicated. It is advised that the neutrophil count should be 1x10 /l and
9
platelets 75x10 /l before giving treatment. Delays of 1-2 weeks are acceptable but delays beyond 2 weeks on
more than one occasion would be an indication to give G-CSF. In case of cytopenia(s) delaying treatment,
G-CSF should be used for the next cycle. CAREFUL FLUID BALANCE MONITORING IS NEEDED DURING GCSF TREATMENT. In case of cytopenia delaying chemotherapy 2 weeks the next cycle should consist of dose
reduction of melphalan to 0.11mg/kg.
c)
Adjustment for renal insufficiency
The dose of melphalan should be reduced to 0.11mg/kg if the serum creatinine is 200mol/l.

Assessment of response and duration of therapy:

All patients should have measurements of the serum free light chain concentration (and paraprotein if detectable
at the onset to treatment) at the end of each cycle of chemotherapy. We can provide this service at the NAC.
Serum or clotted whole blood samples should be sent through the post at ambient temperature and a kit for this is
provided to patients.
Treatment, if tolerated, should be pursued to plateau or best response. We would seldom recommend more than
6 cycles of this protocol, and 3 may be sufficient.
1. ALL PATIENTS MUST BE RE-ASSESSED FOR CLONAL RESPONSE AT THE END OF THE THIRD
CYCLE AND PATIENTS WHO SHOW NO CLONAL RESPONSE AT ALL MUST BE CONSIDERED
FOR AN ALTERNATIVE REGIME.
2. At this time patients who have achieved a complete response (monoclonal protein no longer detectable
and normal free light chains) may stop or receive one further cycle after achievement of CR.
3. Treatment should continue to a plateau or CR for all other patients unless toxicity/adverse events deem
further chemotherapy undesirable.
Choices about continuing or changing treatment will also be governed by the acceptability and adverse effects of
chemotherapy.

Please direct any queries to any of the following:

Dr Julian Gillmore
Dr Ashutosh Wechalekar
Dr Helen Lachmann
Prof Philip Hawkins

020 7433 2726

0207433 2758
020 7433 2804
020 7433 2815

j.gillmore@medsch.ucl.ac.uk
a.wechalekar@medsch.ucl.ac.uk
h.lachmann@medsch.ucl.ac.uk
p.hawkins@medsch.ucl.ac.uk

National Amyloidosis Centre, Royal Free & University College Medical School, Rowland Hill Street, London NW3 2PF, UK
Fax: +44 (0)20 7433 2817 www.ucl.ac.uk/medicine/nac