The results of a recent retrospective study show that multiple myeloma patients who receive a donor stem cell transplant upfront experience better progression-free survival and overall survival compared to patients who receive a donor transplant after relapse or disease progression.

Additionally, the study investigators found that having a related stem cell donor and achieving a complete response after the transplant led to better outcomes. On the other hand, treatment with novel agents prior to the transplant had no effect on survival.

“We have once again confirmed that the benefit from allogeneic [donor] transplantation is greatest when performed early on in the disease. However, in clinical practice, more relapsed and refractory patients are being offered a transplant. There is no randomized data for this patient group, making it all the more urgent to perform a study in this patient group,” said the study’s lead investigator Dr. Sabine Gerull of University Hospital in Basel, Switzerland.

The study investigators conclude that randomized studies analyzing the benefit of donor stem cell transplantation at the time of relapse are still needed.

However, according to Dr. Shaji Kumar of the Mayo Clinic in Rochester, Minnesota, who was not involved with the study, “Randomized trials that have been done in the upfront setting have failed to show any advantage for the allogeneic transplant.”

“I would say that the results here do not have any impact on our view of allogeneic transplant in myeloma. It may offer a treatment option for selected patients, but should preferably be all done under a clinical trial setting,” added Dr. Kumar.

Since the introduction of novel agents such as thalidomide ^[1] (Thalomid), Velcade ^[2] (bortezomib), and Revlimid ^[3] (lenalidomide), the life expectancy of multiple myeloma patients has significantly improved. However for the majority of patients, the disease remains incurable.

Allogeneic (donor) stem cell transplantation gives myeloma patients a chance for long-term remission. In this procedure, patients receive chemotherapy that kills both myeloma cells and healthy stem cells. They subsequently receive stem cells from a healthy donor to replenish the lost blood cells.

Despite their potential in myeloma, donor stem cell transplants are not a common treatment option due to serious risks and complications, such as graft-versus-host disease (GVHD)(see related Beacon ^[4] news). GHVD is a condition in which the donor cells recognize the patient's cells as foreign and attack them.

Previous studies have led to conflicting results regarding whether a donor stem cell transplant is more or less beneficial than other available treatments (see related Beacon ^[5] news).

Furthermore, many prior studies evaluating donor stem cell transplantation are conducted with patients who were pre-treated with conventional chemotherapy.

In the current study, Swiss researchers sought to determine the role of donor stem cell transplantation in the context of novel agents.

They retrospectively analyzed the medical records of 95 myeloma patients who received a donor stem cell transplant in Switzerland between 1988 and 2011.

The median age of the study participants when they were diagnosed was 47 years, and patients received a donor transplant at a median of 22 months after diagnosis.

Prior to the donor transplant, patients had received a median of two lines of therapy; 53 percent of patients were treated with novel agents and 68 percent received an autologous stem cell transplant.

Of the 95 patients included in the study, 49 percent of patients received a donor transplant upfront, while the remaining patients received it after relapse or disease progression. The majority of patients (70 percent) received stem cells from a sibling.

As part of the transplant, patients received high-dose chemotherapy (34 percent), reduced-intensity chemotherapy (44 percent), or non-myeloablative conditioning (22 percent), which uses lower doses of radiation and chemotherapy.

The median follow-up time was 53 months.

Overall, the five-year progression-free survival rate was 29 percent and the five-year overall survival rate was 51 percent.

The study investigators found that patients who received a donor transplant upfront had better two-year progression-free survival (63 percent) compared to patients who received a transplant following relapse or progressive disease (25 percent). They also had better two-year overall survival (81 percent versus 52 percent, respectively).

Furthermore, patients who received zero to two lines of therapy before the transplant demonstrated better two-year progression-free survival and overall survival (55 percent and 73 percent, respectively) than those who received three or more lines of therapy (25 percent and 52 percent, respectively).

Having a related donor was also associated with superior two-year progression-free survival (52 percent) and two-year overall survival (74 percent), compared to having an unrelated donor (25 percent and 48 percent, respectively). Achieving a complete response after the donor transplant also led to improved progression-free survival.

There was no significant difference in progression-free survival or overall survival for patients who received novel agents prior to the transplant versus those who did not.

Patients who received novel agents were more likely than those treated with conventional drugs to receive a transplant after relapse or disease progression (72 percent versus 27 percent), receive more than two lines of chemotherapy prior to transplant (60 percent versus 11 percent), have an unrelated donor (48 percent versus 11 percent), and receive reduced-intensity chemotherapy (80 percent versus 51 percent).

Other factors that did not have an effect on outcome included patient age, the year of transplant, the number of prior autologous transplants, and the type of conditioning regimen.

According to the Swiss researchers, their results are comparable to those of prior studies, which have found an adverse effect of advanced disease on transplant outcomes and improved progression-free survival for patients who reach a complete response after transplant.

Acute GVHD, which develops within the first three months after the transplant, occurred in 58 percent of patients; chronic GVHD, which develops after the first three months following the transplant, occurred in 53 percent of patients.

The donor transplant failed in 3 percent of patients.

Five years post transplant, the treatment-related death rate was 18 percent.

For more information, please see the study in Bone Marrow Transplantation ^[6] (abstract).