Results from a small German study indicate that a stem cell transplant using the patient’s own cells, followed by a transplant using cells from a donor, may improve the prognosis of multiple myeloma patients with high-risk chromosomal abnormalities.

Patients in the study who had high-risk chromosomal abnormalities had similar rates of molecular remission, which is a more stringent form of a complete response, and progression-free survival as patients without high-risk chromosomal abnormalities.

According to the German researchers, their findings show that patients with high-risk chromosomal abnormalities can achieve long-term remission.

However, the treatment protocol used during the trial did result in a substantial number of treatment-related deaths, and it therefore may not be appropriate for many patients.

The goal of myeloma therapy is to ensure long-term remission in patients. With improved treatment options, patients are living substantially longer with the disease. However, most patients eventually relapse, despite advanced treatments and transplant protocols.

Previous research has shown that patients achieving a molecular remission have a high probability of long-term disease control. Molecular remission is a subcategory of complete response, where a more sensitive test is used to determine whether there is still evidence of myeloma in the patient’s bone marrow.

In the current study, German researchers assessed the impact of molecular remission on treatment outcomes in a trial involving recently diagnosed myeloma patients with Stage 2 or Stage 3 disease (according to the Durie-Salmon scale).

Between April 2000 and October 2008, the researchers recruited 73 multiple myeloma patients to receive an autologous transplant followed by a donor (allogeneic) transplant. Autologous transplants use stem cells from the patient’s body, while donor transplants use stem cells from a donor.

The patients in this study were younger than most myeloma patients, with a median age of 49.

Several patients had chromosomal abnormalities, including translocation 4;14 (11 percent) and del17p (11 percent). Patients with t(4;14), which is a translocation of a region of chromosome 4 to chromosome 14, and del17p, which is a deletion of a portion of chromosome 17, are considered high-risk patients.

Prior to receiving their first transplant during the trial, most patients received initial anti-myeloma therapy involving one of several older myeloma treatment regimens, such as combination therapy with vincristine ^[1] (Oncovin), doxorubicin ^[2] (Adriamycin), and dexamethasone ^[3] (Decadron).

However, some patients who joined the trial in its later years received initial therapy that included a newer anti-myeloma agent, such as Velcade ^[4] (bortezomib).

Most patients in the trial received only one treatment regimen between their diagnosis and the transplants that took place during the trial.  There were, however, some patients who did not respond to their initial treatment who received salvage therapy before the transplants in the trial.

As high-dose therapy before their autologous transplant, each patient received 200 mg/m² of melphalan ^[5] (Alkeran) divided over two days before the transplant.

Prior to their donor transplant, each patient received a reduced dose of 140 mg/m² of melphalan and 180 mg/m² of fludarabine (Fludara), as well as antithymocyte globulin (ATG) to help reduce the risk of graft-versus-host-disease (GVHD).  GVHD is a  transplant-related complication in which the donor cells recognize the patient’s cells as “foreign” and attack them.

About one fifth of the patients in the trial also received donor lymphocyte infusions after their donor transplant.  Donor lymphocyte infusion is a procedure in which white blood cells are collected from a patient’s stem cell donor and infused into the patient sometime after the donor stem cell transplant. This was done during the trial in patients who either still had signs of their own original immune system after the donor transplant, or who had signs of residual disease after the transplant.

The median time between the two transplants was 110 days. The median follow-up time was six years.

Overall, 60 percent of the patients in the trial achieved a complete response, 6 percent a near complete response, and 21 percent a partial response.

Additionally, 41 percent of patients achieved a molecular remission. The molecular remission rate was slightly higher in patients with del 17p or t(4;14) compared to patients without these abnormalities (50 percent versus 40 percent).

Twenty-one percent of patients achieved a sustained molecular remission, which the researchers defined as the achievement of at least four consecutive bone marrow samples negative for myeloma. The sustained molecular remission rate was slightly lower in patients with high-risk chromosomal abnormalities compared to patients without them (8 percent versus 12 percent).

The five-year progression-free survival rate for all patients was 29 percent and did not differ significantly between patients with or without high-risk chromosomal abnormalities (24 percent versus 30 percent, respectively).

There was a difference in five-year progression-free survival, however, depending on whether or not a patient achieved a complete response after their second transplant.  Those who achieved a complete response had a significantly higher progression-free survival than those who did not (41 percent versus 17 percent).

Moreover, patients who achieved a molecular remission had a better five-year progression-free survival rate than those who had a complete response without molecular remission (57 percent versus 26 percent).

There were even differences in progression-free survival among the patients with a molecular remission.  Those who had a sustained molecular remission had a significantly higher five-year progression-free survival than those whose molecular remission was not sustained (85 percent versus 31 percent).

The impact of depth of response – that is, how complete a patient's response to treatment was – is also evident in the overall survival results from the study.

The five-year overall survival rate for all patients was 54 percent. Patients with a complete response had a 74 percent five-year survival rate versus 38 percent for those who did not achieve a complete response.

Likewise, patients who achieved a molecular remission had a better five-year overall survival than those who did not (89 percent versus 39 percent).  There also was a trend for the five-year overall survival to be higher in patients with a sustained molecular remission versus those whose molecular remission was not sustained (91 percent versus 87 percent).

The authors of the current study did not report whether there was any differences in overall survival between patients with or without high-risk chromosomal abnormalities.  However, in correspondence with The Myeloma Beacon, the lead author of the study - Dr. Nicolaus Kröger from the University Medical Center in Hamburg, Germany - clarified that there was, in fact, no significant difference in overall survival between patients with or without high-risk abnormalities.

Although the double transplant regimen pursued during this trial did achieve a very deep response in a number of patients, it also was accompanied by substantial risk.  Ultimately, 23 percent of the patients in the trial died during their first year of therapy due to the treatment itself.

For more information, please see the study in Biology of Blood and Marrow Transplantation ^[6] (abstract).