The results of a small, retrospective study indicate that donor stem cell trans­plan­ta­tion may be effective and well tolerated in multiple myeloma patients who have a deep response to initial therapy.

Specifically, the researchers found that for the majority of patients, stem cell trans­plan­ta­tion deepened their initial response to a complete or stringent com­plete response.

Two years following transplantation, three-quarters of the patients were disease-free, which according to the researchers shows that donor transplantation may be a good tool for the pre­ven­tion of early relapse and progression of the disease.

However, the study investigators point out that a larger number of patients will be needed to evaluate the effi­cacy of donor transplantation as consolidation therapy (following initial therapy). A Phase 2 study is cur­rent­ly underway to follow up on these findings.

Background

Autologous stem cell transplantation is frequently used as early treatment in myeloma patients up to 65 years of age. In this process, the patient’s own stem cells are collected before receiving high-dose chemo­therapy, which destroys the cancerous cells as well as the patient’s healthy bone marrow cells. The stem cells are then returned to the patient following chemotherapy, and the stem cells eventually mature to re­place the destroyed cells.

The role of donor (allogeneic) stem cell transplantation in multiple myeloma, however, is still controversial. In this procedure, the patient receives stem cells from a matched donor instead of from his or her own body.

Although donor transplantation gives myeloma patients a better chance for a cure than autologous trans­plan­ta­tion, it also carries a greater risk of life-threatening diseases such as graft-versus-host disease (GVHD), a condition in which immune cells from the donor attack the recipient’s cells.

Because of these risks, donor stem cell transplants are mostly done in the context of clinical trials.

Consolidation therapy is a short course of treatment meant to deepen a patient's response to prior treat­ments. It is different from maintenance therapy, which typically involves a longer regimen meant to prevent disease progression while maintaining a favorable quality of life.

According to the investigators of the current study, the use of donor stem cell transplantation as con­soli­da­tion therapy has not been well studied.

They therefore sought to investigate the efficacy of donor transplantation as consolidation therapy in patients who had reached a very good partial response or a complete response after initial therapy.

Study Design

Researchers from the Lee Moffitt Cancer Center in Tampa, Florida, retrospectively analyzed data from 22 multiple myeloma patients who, between 2007 and 2012, had achieved a very good partial response or a complete response after initial therapy with Velcade ^[1] (bortezomib) or Revlimid ^[2] (lenalidomide) and went on to receive a donor transplant as consolidation therapy. The median patient age was 49 years.

Patients had received either Velcade plus fludarabine (Fludara) and melphalan ^[1] (Alkeran) or fludarabine and melphalan alone as a reduced-intensity conditioning regimen prior to donor transplantation.

Patients in the Velcade-conditioning group received 30 mg/m² of fludarabine for four straight days up until the third day before trans­plan­ta­tion, 70 mg/m² of melphalan for two days up until the third day before trans­plan­ta­tion, and 1.3 mg/m² of Velcade immediately after the last dose of melphalan.

Patients who did not receive Velcade as part of their conditioning regimen received 40 mg/m² of fludarabine for four days up until the third day before trans­plan­ta­tion and 70 mg/m² of melphalan for two days until the third day before trans­plan­ta­tion.

The researchers also retrospectively identified 41 myeloma patients with similar characteristics who re­ceived an autologous transplant to serve as a comparison group. These patients had a median age of 54 years and had reached their first very good partial response or complete response just prior to trans­plan­ta­tion.

Study Results

Prior to receiving a donor transplant, 27 percent of patients achieved a stringent complete response. This measure increased to 68 percent after donor transplantation.

Of the patients who had reached a very good partial response prior to donor transplantation, 33 percent im­proved their response to a complete response and 42 percent improved to a stringent complete response fol­low­ing donor transplantation.

Among the patients who underwent autologous transplantation, 21 percent of patients reached a complete response and 57 percent reached a stringent complete response after transplantation.

Two years post-transplant, 8 percent of patients in the donor transplant group relapsed, compared to 46 percent in the autologous transplant group.

The estimated two-year progression-free survival rate for patients who underwent donor transplantation was 75 percent, compared to 52 percent for patients who underwent autologous transplantation.

The estimated two-year overall survival rate for the donor transplant group was 78 percent, versus 90 per­cent for the autologous transplant group.

Graft-versus-host disease (GVHD) was a common side effect among patients undergoing donor trans­plan­ta­tion.

Overall, 45 percent of patients experienced moderate to severe acute GVHD, which occurs within 100 days of transplantation. Furthermore, 46 percent of patients experienced chronic GVHD, which occurs 100 or more days after transplantation.

After donor transplantation, 18 percent of patients died of GVHD-related complications and 5 percent died from disease progression.

For more information, please see the study in the journal Bone Marrow Transplantation ^[3] (abstract).