Updated Results of the Phase II Study of Pegylated Liposomal Doxorubicin (PLD), Low Dose Dexamethasone (DEX) and Lenalidomide (LEN) In Patients with Newly Diagnosed (ND) Multiple Myeloma (MM)

We previously reported the interim results of a phase II trial of PLD, low dose DEX and LEN in patients with NDMM. After a median of 4 cycles, the overall response rate (ORR) was 71% with 50% of patients achieving VGPR or better (ASCO 2009 Ann Meeting Proc #8518). However, due to a high rate of grade 3/4 fatigue and neutropenia, a dose reduction in PLD was recommended in order to improve tolerance and avoid treatment interruption. We herein report the updated results of this combination.

The first 29 patients received PLD (40 mg/m2 on day 1), DEX (40 mg on days 1–4) and LEN (25 mg Days 1–21) every 28 days (for 2 cycles beyond best response). Prophylactic low dose aspirin, acyclovir and fluoroquinolone were recommended. Patients not eligible or not wishing to proceed with high-dose therapy continued on the tolerated dose of LEN and DEX until disease progression or unacceptable toxicity. PLD was reduced to 30 mg/m2 after the first 29 patients as described in background section.

Between 2/2008 and 7/2010, 47 of a planned 60 patients were enrolled. 3 patients were screen failures and are not included in subsequent analysis. The mean age was 63 years (36-78) and 53% were males. The median β2microglobulin was 2.8 mg/dL (21% had β2m>3.5). Using the IMWG criteria and after a median of 6 cycles of therapy, 5 patients had CR or sCR, 15 patients had VGPR, 14 patients had a PR, 6 patients had SD, 1 patient had PD, 3 patients were not evaluable (failure to complete 1 cycle of therapy for reasons other than PD). The overall response rate was 83% with 49% VGPR and better. For the cohort of patients treated after the dose reduction of PLD, the ORR was 88%, and VGPR and better was noted in 50%. In the patients treated with the reduced dose of PLD, no grade 4 toxicities were noted and the following grade 3 toxicities were noted: neutropenia (25%), fatigue (12.5%), infections (18%, only 1 patient had febrile neutropenia). No grade 3 or 4 venous thromboembolic events, anemia and thrombocytopenia were noted. This compares favorably with 48%, 10%, 7%, 21%, and 20% grade 3/4 neutropenia, anemia, thrombocytopenia, fatigue and infections, respectively, in the 29 patients treated at the higher dose of PLD. 18 patients proceeded to high-dose therapy (median CD34+ 4.24×10⁶, 8 patients had stem cell collection with GCSF alone, 8 with AMD3100, 2 with cyclophosphamide). 9 patients received maintenance therapy with lenalidomide and dexamethasone. Survival and progression free results remain immature.

The combination of PLD, LEN and DEX is an active regimen in patients with NDMM. The dose reduction of PLD in this regimen resulted in better tolerance without a compromise in efficacy due to less frequent treatment interruptions.

Baz:celgene: Consultancy, Research Funding; millenium: Research Funding; orthobiotec: Research Funding. Off Label Use: use of pegylated liposomal doxorubicin and lenalidomide in newly diagnosed myeloma rather than in relapsed or refractory myeloma. Hussein:celgene: Employment. Sullivan:Merck: Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees; Merrion: Membership on an entity's Board of Directors or advisory committees. Alsina:Millennium Pharmaceuticals, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding; Ortho Biotech: Research Funding.