Hematopoietic Stem Cell Transplant Program at Roswell Park: Endeavors to Improve Outcomes of Multiple Myeloma


Multiple myeloma is a malignant disorder involving clonal expansion of plasma cells in the bone marrow. It is an incurable hematological malignancy, and therapeutic strategies to achieve long-term control require autologous hematopoietic stem cell transplant. In the past few years treatment of this disease has evolved significantly with utilization of novel agents including proteasome inhibitors and immunomodulatory drugs like lenalidomide.

Lenalidomide Slows Disease Progression, Prolongs Survival in Phase III Study

A phase III, randomized, double-blind, placebo-controlled trial, led by Roswell Park Comprehensive Cancer Center investigators, established that lenalidomide maintenance therapy after autologous hematopoietic stem cell transplant significantly prolonged time to progression as well as overall survival in patients with multiple myeloma. A total of 460 patients, having undergone hematopoietic stem cell transplantation, were randomized at day 100 after stem cell transplant to lenalidomide or placebo until disease progression. Eligibility criteria included age less than 71 years and presence of stable disease or a marginal, partial, or complete response.

At planned interim analysis there was significant improvement in time to progression (20% disease progression in lenalidomide group vs. 44% in placebo group, P<0.001). In their final publications in the New England Journal of Medicine, the authors reported a significant difference in the median time to progression (46 months vs. 27 months P<0.001) as well overall survival with addition of maintenance lenalidomide. Fifteen percent of patients in lenalidomide group vs. 34% in placebo group died at a median follow-up of 34 months (p=0.03).

Expanding on Lenalidomide Study Results with Two Additional Studies

The efforts to further improve the outcome and ultimately find curative therapy for this disease are ongoing. Roswell Park investigators are currently evaluating various treatment strategies directed to this goal. Notable amongst them are two ongoing clinical trials that have been designed to advance the results of the abovementioned phase III lenalidomide trial.

Clinical Trial #1:

The first trial is aimed at evaluating and comparing clinical outcome with tandem transplants versus single autologous transplant followed by consolidation and maintenance therapy. This is especially relevant in the era of novel and efficacious therapies like proteasome inhibitors and immunomodulatory drugs. This trial, being conducted through the Blood and Marrow Transplant Clinical Trials Network, is a three-arm randomized phase III study evaluating “Single Autologous Transplant With or Without Consolidation Therapy Versus Tandem Autologous Transplant With Lenalidomide Maintenance for Patients With Multiple Myeloma.”

Additionally, Roswell Park is working in collaboration with other investigators of this study to standardize the parameters that define minimal residual disease in correlation with clinical outcome.

Clinical Trial #2

The second trial is focused on evaluating the necessity of autologous stem cell transplant in front-line setting for multiple myeloma. This is a Phase III, multicenter, randomized, open-label study designed to evaluate the clinical benefit from the drug combination Lenolidomide/ Bortezomib /Dexamethasone (RVD) without immediate autologous stem cell transplant followed by lenalidomide maintenance (Arm A) versus RVD plus autologous stem cell transplant followed by lenalidomide maintenance (Arm B).

Read more: A Randomized Phase III Study Comparing Conventional Dose Treatment Using a Combination of Lenalidomide, Bortezomib and Dexamethasone (RVD) to High-Dose Treatment with Peripheral Stem Cell Transplant in the Initial Management of Myeloma in Patients up to 65 Years of Age