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)
Authors: Baz Rachid , Hussein Mohamad A , Sullivan Daniel , Ochoa-Bayona Jose-Leonel , Hartley Monique A , Shain Kenneth , Nishihori Taiga , Paleveda Jennifer , Kosakowski Kara , Dalton William S. , Alsina Melissa 
Published: October 2019

Abstract
Abstract 3054

Background:
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.

Methods:
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.

Results:
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.

Conclusion:
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.

Disclosures:
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.