Multiple myeloma (incidence:3-5/100,000 people) Diagnostic triad: plasmacytosis(> 10%) + M-spike/Bence Jones protein + osteolytic lesion

MULTIPLE MYELOMA (incidence:3-5/100,000 people) Diagnostic triad: plasmacytosis(> 10%) + M-spike/Bence Jones protein + osteolytic lesion

Clinical triad: bone pain + anemia + renal insufficiency 98-99% of patients will have a monoclonal protein in serum/urine lgG=60%, lgA=20%, Bence Jones (only)= 10%, lgD=1%, lgE=0.01% Prognosis: stage dependent (e.g., IA=~62 months;IIIB~15 months)

start chemotherapy if stage IB-IIIB

Melphalan (0.25 mg/kg or 9 mg/m² for 4 days or 0.15 mg/kg for 7 days) Prednisone 50 mg bid for 4 days or 20 mg tid for 7 days

take melphalan in fasting state (food J- absorption > 1/3)

q 5-6 weeks (encourage patient to walk and drink at least 2-3 L of fluids/day) avoid diuretics analgesic on fixed schedule

Continue treatment as long as M-protein continues to decline

yes(4-6 months)

BMT (allogenic if donor available) or autologous BMT

Obtain CBC q 2-3 weeks after 1 cycle (to monitor melphalan bioavailability;

if some degree of leukopenia and thrombocytopenia is observed continue with same dose; if CBC unchanged increase dose of melphalan 2-4 mg/day cycle until leukopenia/thrombocytopenia is observed;

withold treatment if WBC <2,500/ccu (ANC<1,800/ccu) or platelet<100,000/ccu)

Maintenance treatment:

interferon «-2b 3 MU/m² 3 times a week SC (see CML chapter for side effects)

Response to treatment:

Serum M-protein decreases to < 50% of the pretreatment value on 2 separate measurements (taken at 4 week intervals)

Urine M-protein decreases to < 10% of pretreatment value (changes not considered significant if there is renal failure)

resistant

30-50%

relapse

(progression on

initial treatment or failure

to acheive initial response)

Check CBC before each chemotherapy cycle

Treatment monitoring—determine

CBC before each treatment cycle (see Fig. 38-2)

Calcium, creatinine q 1-2 months

SPE and IPE to follow M-spike concentration

q 2 months (SPE more reliable than IPE

if M-peak visible) 24 h urine collection for total protein and light

chain analysis (q 2-3 months) /?2-microglobulin in q 2 months Skeletal x-ray survey (q 6-12 m) Marrow aspirate if pancytopenia develops

(to distinguish between multiple myeloma

50-60%

chance for response

VAD + verapamil

and treatment effect)

VAD regimen:

(40% response)

Vincristine 0.4 mg and doxorubicine 9 mg/m² for 4 days in continuous infusion

Dexamethasone 40 mg for 4 days starting on days 1, 9 and 17 q 28 days

Antacids/H2 blockers and trimethoprim-sulfamethoxazole for prophylaxis (1 DS bid)

Anti-emetics before treatment

Glucorticoids:

Dexamethasone 40 mg for 4 days starting on days 1, 9 and 17 q 28 days; or prednisone 100 mg qod (decrease dose to 50% qod if response is noted)

Antacids/H2 blockers and

trimethoprim-sulfamethoxazole for prophylaxis (1 DS bid)

| 2 cycles

Continue as long as response is achieved;

after maximal response, give 4 additional cycles before treatment is stopped

yes

no

Third line treatment:

EDAP or cr-interferon 3 MU/m² 3 times a week or sequential hemibody irradiation

Determine glycoprotein P-170 (multidrug resistance protein)

cannot be assayed

or negative