A new study by Spanish researchers sheds light on the role of stem cell transplantation in the treatment of newly diagnosed multiple myeloma.

The study focuses on newly diagnosed patients who, in a clinical trial, did not respond to initial rounds of chemotherapy to treat their disease.

It finds that, among these non-responding patients, the ones who had stable disease after their initial round of chemotherapy responded well to stem cell transplantation.

In contrast, the patients whose disease not only did not respond to initial therapy, but continued to progress, got little or no benefit from stem cell transplantation.

The Spanish researchers point out that their results confirm the need for new treatment approaches, including experimental drugs, for myeloma patients whose disease continues to progress after initial therapy.

Dr. Peter Voorhees, hematologist and internist at the University of North Carolina Chapel Hill, who was not involved in the study, agrees with the Spanish researchers that patients with disease that progresses in the face of induction therapy were not well served by autologous stem cell transplantation. "For myeloma patients whose disease continues to progress after initial therapy, the focus should be on better defining their disease biology.  Such research may help lead to the development of new therapies that will have a greater impact on their disease," said Dr. Voorhees.

The new study is based on a retrospective analysis of data for 80 multiple myeloma patients who participated in a Spanish clinical trial known as PETHEMA/GEM-2000.

The 80 patients were diagnosed between 1999 and 2004, and all of them received multiple cycles of initial ("induction") chemotherapy  followed by at least one stem cell transplant.  Half of the patients also received a second stem cell transplant.

The first stem cell transplant for all patients was an autologous transplant, in which patients are infused with their own stem cells collected prior to high-dose chemotherapy designed to kill most of patients' remaining stem cells.

The majority of the second transplants also were autologous transplants.  However, about a quarter of the second transplants were allogeneic transplants, in which stem cells from a donor are used for the transplant.

Currently, almost all younger myeloma patients receive a stem cell transplant at some point during the treatment of their disease.  The increasing use of stem cell transplantation in the treatment of younger myeloma patients is considered one of the reasons the average survival of these patients has increased over time (see related Beacon news).

There remains some controversy, however, regarding which patients benefit most from the procedure (see related Beacon news).

All of the 80 patients in the Spanish study were considered "refractory" (not responsive) to their initial cycles of chemotherapy.  Patients were considered refractory if they never achieved a minimal response or better following induction therapy.

The Spanish researchers divided the 80 refractory patients further into the following two subgroups: those whose disease did not respond, but remained stable, after their induction therapy; and those whose disease was "progressive" -- that is, continued to progress -- after the induction therapy.

Of the 80 refractory patients, 61 percent were classified as having stable disease following initial therapy, and 39 percent were classified as having progressive disease.

In their analysis, the researchers focused on differences in response rates and survival times between the two groups of refractory patients.

The researchers did not find any statistically significant differences in the percentages of patients achieving a partial response or better to the first stem cell transplant.

Among the refractory patients who had stable disease, 54 percent had a partial response or better to the first stem cell transplant, compared to 58 percent among the patients with progressive disease.

Among the patients with stable disease, however, 38 percent remained in stable condition or achieved minimal response after the first stem cell transplant, compared to just 7 percent of the progressive disease patients.

Furthermore, more than a fifth of the patients in the progressive disease group saw their disease continue to progress within three months of the first stem cell transplant, compared to just 2 percent of the stable disease patients.

The differences between the two groups in terms of disease stability and rate of progression also were reflected in survival time differences.

Median overall survival after the first stem cell transplant was 1.1 years in the progressive disease group and 6 years in the stable disease group.

Median progression-free survival likewise differed significantly between the two groups of patients; 0.6 years compared to 2.3 years, respectively.

According to the Spanish researchers, the overall and progression-free survival times for the refractory patients with stable disease are similar to those of non-refractory patients -- that is, patients who responded to their induction therapy.

This suggests that stem cell treatment is beneficial for refractory patients provided their disease is stable after induction therapy.

It also is possible, the authors note, that the stable refractory patients may simply have a less aggressive form of myeloma, which on its own would lead to extended survival times.

In contrast, the researchers believe their analysis is more conclusive in regard to refractory patients whose disease continues to progress after induction therapy.  These patients do not appear to benefit from a stem cell transplant.

Dr. Voorhess points out, however, that there are two caveats to the Spanish researchers study.  First, he notes that some patients in the study were treated with a tandem transplant approach.  It is, therefore, unclear whether a single autologous stem cell transplant would produce effects in patients with stable disease on induction therapy.

He also points out that that the patients in the study were treated with conventional chemotherapy for induction rather than with novel agents.  “Stable disease on Revlimid (lenalidomide) / Velcade (bortezomib) / dexamethasone (Decadron) induction therapy is likely a different animal than stable disease on conventional chemotherapy,” he states.

For more information, see the article in the journal Haematologica (pdf).