Pegylated Liposomal Doxorubicin (PLD), Dexamethasone and Low Dose Thalidomide (DDt): An Active Regimen in the Frontline Therapy for Multiple Myeloma (MM).

Objectives and Methods: Thalidomide/dexamethasone is considered one of the current standard induction therapies for MM. We evaluated efficacy and toxicity of adding PLD to dexamethasone and low dose thalidomide. Stem cell harvest yield and QOL using FACT-G/Fact-Leu Tools were also assessed. Patients were treated with PLD (Doxil®) 40mg/m2 IV d1, thalidomide 100 mg PO Q HS, and dexamethasone 40 mg PO d1–4 and 15–18 Q 28 days for up to 4 cycles. Eligible patients subsequently underwent autologous stem cell harvest and transplant. Patients received prophylactic antimicrobials, erythropoietin injections and biphosphonate therapy.

Results: Between 8/03 and 3/07, 25 patients were enrolled; 1 excluded for incorrect diagnosis. Median age 61 (49–79yrs); 17 males. Subclasses included IgGλ-9, IgGκ-7, non-secretory-3, IgAκ-2, IgAl-2 and κ light chain-1. At presentation, the patients had Drurie Salmon Stage IA-2, IB-1, IIA-5, IIIA-11, IIIB-5 (ISS stage 1–10, 2–8 and 3–6). Median B2M 3.5 (range: 1.1–41 mg/L). Eleven patients completed 4 cycles; one withdrew after cycle 1; 10 were taken off study (8 due to grade 3–4 toxicity: 5-infection, 1 acute renal failure, 1 dehydration and 1 arrhythmia; and 2 due to treatment delays more than 2 weeks secondary to infection). Median cycles received prior to being taken off study were 2. Two patients developed venous thrombotic events (VTE): one after cycle 1 while on low dose coumadin; another died of pulmonary embolism after cycle 1, while on aspirin, requiring amendment of protocol to therapeutic doses of coumadin. No further VTE were observed. There was another death due to pneumonia after cycle 2. Thirteen patients underwent stem cell harvest with cyclophosphamide and growth factor mobilization. The median harvest yield was 5.76 x106 CD34/kg (range: 3.87 – 31.94); median harvest days-3 (range: 1–7). Of the 20 patients who received at least one cycle and assessable for response, the ORR was 95% using SWOG/IBMTR criteria: PR-35%/75%; VGPR–40%/nCR-5%; CR-20%/15%; 1 had PD. The median serum M-protein response after cycle 1 (n=19): −53% (+17 to−86%), cycle 2 (n=18): −80.5% (−38% to −100%). One patient achieved CR after 2 cycles. Further responses after the 3rd and 4th cycles were minimal. The scores in most of the Fact-G/Fact-Leu subscales showed increasing trend corresponding to overall improvement in the patient’s QOL throughout the course of therapy as compared to baseline. The improvement was most noted in the emotional well-being subscale.

Conclusions: DDt represents an active induction therapy for patients with MM. Major responses and treatment-related toxicity occur early in the course of therapy, arguing for early stem cell harvest and autologous transplant after two cycles of treatment. No adverse impact on stem cell harvest is associated with this therapy. Full dose anticoagulation to prevent VTE is essential when using this combination regimen. The overall QOL of patients improved while on treatment as compared to baseline.