Findings from a recent retrospective study indicate that a second autologous stem cell transplant may be an effective and safe salvage therapy for certain relapsed and refractory multiple myeloma patients.

In particular, the researchers found that the second stem cell transplant was particularly effective for patients who did not progress for at least 12 months following the first stem cell transplant.

For patients who relapse more quickly, the researchers recommend salvage therapy with novel agents, such as Velcade (bortezomib), thalidomide (Thalomid), Revlimid (lenalidomide), or investigational drugs.

High-dose chemotherapy followed by autologous stem cell transplantation is a common treatment option for patients with multiple myeloma. The procedure involves collecting a patient’s own stem cells before the patient receives high-dose chemotherapy, which destroys both healthy and cancerous cells. The stem cells are then re-infused into the patient to replace the destroyed cells.

However, according to the researchers, most patients relapse after an initial stem cell transplant. Thus, they require further treatment, which is known as salvage therapy. Drug-based regimens involving novel agents have already been shown to be effective salvage therapies (see related Beacon news).

Previous studies have shown that second transplants may be an effective salvage therapy for relapsed and refractory multiple myeloma patients (see related Beacon news).

However, according to the investigators from the Mayo Clinic, the previous studies only involved small numbers of patients.

They therefore retrospectively analyzed the records of 1,033 patients who underwent an initial stem cell transplant at their institution between 1994 and 2009. Of this group, 153 patients went on to undergo a second stem cell transplant, and 64 percent of those 153 patients received the second transplant as a salvage therapy. The remaining patients received the second transplant as part of an upfront tandem protocol; these patients were not included in the subsequent analysis.

The median age of the patients who received the second transplant as salvage therapy was 54 years at diagnosis and 60 years at the time of the second transplant.

The median time between the first and second transplant was 46 months.  The median time between relapse after the first transplant and the second transplant was 14.5 months.

Patients received a median of three regimens between the two transplants; 50 percent of patients received treatment with Velcade, 40 percent with Revlimid, and 32 percent with thalidomide.

The median follow-up time from diagnosis was 129 months.

The investigators reported that 87 percent of patients responded to the second transplant, with 31 percent achieving a complete response, 20 percent achieving a very good partial response, and 36 percent achieving a partial response. The researchers described these response rates as comparable to those of salvage therapies with novel agents.

The median progression-free survival time after the second transplant was 10.3 months. The researchers found that a short duration of response after the first transplant, more lines of therapy before the second transplant, and not achieving a complete response after the second transplant were associated with shorter progression-free survival times.

The median overall survival times were 8.5 years from diagnosis and 2.75 years from the time of the second transplant.

The researchers also found that only a shorter duration of response after the first transplant was associated with a shorter overall survival time. For example, patients who progressed within 12 months of their first transplant had significantly shorter overall survival times after their second transplant (12.6 months) than patients who progressed more slowly (43 months).

The researchers then compared the survival data for these patients who underwent a salvage transplant to that of patients with similar disease characteristics who had not received a second transplant as salvage therapy. They found that the median overall survival time from diagnosis was longer for patients receiving a second transplant (8.5 years) than for patients not receiving a second transplant (7.7 years).

According to the investigators, the second transplant had an acceptable safety profile. The most common side effects were the presence of bacteria in the bloodstream (31 percent) and mouth ulcers (27 percent). Four percent of the patients died due to treatment-related causes, which, according to the investigators, indicates a favorable benefit-risk ratio.  

The researchers note that 83 percent of patients have relapsed to date and that 73 percent have received additional salvage therapies after the second transplant.

For more information, please refer to the study in Bone Marrow Transplantation (abstract).