Results of a retrospective British study add to the body of research indicating that a second stem cell transplant can be effective salvage therapy for certain relapsed multiple myeloma patients.

The British researchers found that patients who achieved a long re­mis­sion after their first transplant were more likely to have a long remis­sion after their second transplant.  This finding has been seen in previ­ous research on the issue (see related Beacon news articles 1, 2, and 3).

The British investigators also found signs that treatment with Vel­cade (bortezomib) after a patient's first transplant may extend survival after the second transplant.

However, when the researchers controlled for the different factors that might affect a patient's survival after a second transplant, they found only one factor had a significant independent impact: the patient's disease status prior to the second transplant.

The deeper a patient's remission at the time of their second transplant, the longer they survived after the transplant.

The researchers recommend larger clinical trials to confirm these results and to better define the role of salvage transplantation in multiple myeloma.

A common treatment option for myeloma patients is an autologous stem cell transplant.  The transplant process starts with a patient’s own stem cells being collected.  Next, the patient receives the actual treatment that is part of the process, which is high-dose chemotherapy. Finally, the patient's stem cells are re-infused into the patient to replace the healthy cells destroyed by chemotherapy.

The British researchers point out that most patients relapse after their first stem cell transplant and require further treatment, known as salvage therapy. While treatment with newer anti-myeloma drugs has shown promise as salvage therapy, there is, according to the British researchers, little data available regarding the efficacy of a second transplant.

To shed further light on the issue, the British researchers retrospectively analyzed the records of 83 patients who received a second stem cell transplant as salvage therapy.  Most of the transplants were performed after 1999, with 41 percent performed in the years 2000-2005, and 58 percent in the years 2006-2011.

The median patient age was 61 years at the time of the second transplant.

The researchers were also interested in studying whether ethnicity was a predictor of success after the second transplant. Overall, 72 percent of patients in the author's study were Caucasian, 13 percent were of African descent, and 15 percent were of Asian descent.

Most of the patients (77 percent) received novel agents such as Velcade, thalidomide (Thalomid), or Revlimid (lenalidomide) after the first transplant and before their second transplant.

More patients received a reduced dose of melphalan (Alkeran) before the second transplant than before the first (54 percent versus 23 percent, respectively).

The median time to progression after the first stem cell transplant was 21.5 months, and the median time between the first and second transplant was 35.4 months.

Following the second transplant, the median progression-free survival was 15.5 months and the median overall survival was 31.5 months.

Once they controlled for several different factors that might affect progression-free survival after the second transplant, the researchers found that only two factors were statistically significant: time to progression following the first transplant, and disease status at the time of the second transplant

In addition, only disease status at the time of transplantation had a significant independent effect on overall survival.

There were signs in initial analyses done by the authors that several factors – such as length of remission after the patient's first transplant, and treatment with Velcade after the first transplant – might affect overall survival after the second transplant.

However, once the authors controlled for all the factors that might affect survival, only disease status at the time of the transplant was statistically significant.

Patients who, at the time of their second transplant, were still in a relatively deep response to their prior therapies lived longer than other patients.

The median three-year overall survival rate was 47 percent for all patients in the authors' sample. Patients who received the second transplant while in a very good partial response or better had a significantly better three-year overall survival rate (86 percent), compared to patients in a partial response (51 percent) and patients not in a partial response (24 percent).

For more details on the relationship between overall survival and disease status prior to the second transplant, see the overall survival graph on the right. (Clicking on the graph will display a larger version of it.)

According to the investigators, ethnicity did not play a role in the success of the second transplant after they controlled for other factors that could affect survival, such as disease state. The authors believe this result fits well with the findings of previous research. Several other studies have shown that race is not an independent factor affecting a myeloma patient's response to stem cell transplantation.

While the investigators did not publish detailed safety data related to the second transplant, they stressed that the second transplant was very effective in these patients even though they were heavily pre-treated.

That said, 7 percent of the patients in the sample died within 100 days of the second transplant due to causes other than disease relapse.

For more information, please see the study in the journal Leukemia and Lymphoma (abstract).