Long-term follow-up results of a European study indicate that an autologous stem cell transplant followed by a “mini” donor stem cell transplant may be more effective than one or two autologous stem cell transplants in multiple myeloma patients.

“The results show that [“mini”] donor stem cell transplantation was superior to autologous stem cell transplantation concerning relapse rates and long-term progression-free survival and overall survival,” said Dr. Gösta Gahrton of the Karolinska University Hospital in Sweden and one of the study authors.

“The results have strengthened the role of this type of treatment program in multiple myeloma and may lead to more patients being considered for this treatment,” he added.

However, Dr. Ravi Vij of the Washington University School of Medicine in St. Louis, who was not involved in the study, stated that longer follow-up of additional studies that have so far been reported with short follow-up are needed before considering all eligible myeloma patients as candidates for donor stem cell transplantation.

“I don’t think [this study] will have immediate practice-changing implications because we do have other trials that seem to contradict the findings of this trial,” Dr. Vij told The Myeloma Beacon.

Current Role Of Transplantation In Multiple Myeloma

Autologous stem cell transplantation is the current standard of care for myeloma patients up to 65 years of age. In this process, the patient’s own stem cells are collected before receiving high-dose chemotherapy, which destroys both healthy and cancerous cells. The stem cells are then returned to the patient following chemotherapy and eventually mature to replace the destroyed cells.

The role of donor (allogeneic) stem cell transplantation in multiple myeloma, however, is still controversial. In this procedure, the patient receives stem cells from a matched donor instead of from his or her own body.

Although donor transplantation gives myeloma patients a better chance for a cure than autologous transplantation, it also carries a greater risk of life-threatening diseases such as graft-versus-host disease (GVHD), a condition in which white blood cells from the donor attack cells in the recipient, and serious infections.

Because of these risks, Dr. Vij explained that donor stem cell transplants are mostly done in the context of clinical trials.

A new procedure known as non-myeloablative, or “mini,” donor stem cell transplantation is considered safer for myeloma patients because it uses lower doses of chemotherapy and radiation than traditional donor stem cell transplants.

“[Traditional donor transplantation] is associated with a high risk of transplant-related death, which results in a poorer outcome for patients compared to [“mini” donor transplantation],” explained Dr. Gahrton.

Study Design

In this study, researchers aimed to determine whether a “mini” donor stem cell transplant following an autologous stem cell transplant yields a survival benefit compared to autologous stem cell transplant alone in myeloma patients.

The study included 357 previously untreated multiple myeloma patients. The 108 patients who had a matched donor were placed into the auto-allo treatment group, which received an autologous transplant followed by a “mini” donor transplant. The 249 patients who did not have a matched donor were placed into the auto treatment group, which received one or two autologous transplants.

Patients in the auto-allo treatment group had a median age of 54 years, and patients in the auto treatment group had a median age of 57 years.

Twenty-seven percent and 25 percent of patients in the auto-allo and auto groups, respectively, had the chromosomal abnormality del(13q14), which the study authors identified as a marker for poor prognosis in myeloma patients.

All patients had received a combination of vincristine ^[1] (Oncovin), doxorubicin ^[2] (Adriamycin), and dexamethasone ^[3] (Decadron), or a similar combination as induction therapy. They then received 200 mg/m² of melphalan ^[4] (Alkeran) followed by an autologous stem cell transplant.

Of the 108 patients in the auto-allo group, 84 percent then received a preparative regimen of 30 mg/m² of fludarabine daily for three days followed by a “mini” donor transplant. The other patients in the auto-allo group did not continue with treatment for various reasons, most commonly because of disease progression.

Of the 249 patients in the auto group, 58 percent received only the first autologous stem cell transplant, while 42 percent received a second autologous transplant

Study Results

After a median follow-up time of 60 months, researchers found that patients in the auto-allo group had a higher complete response rate (51 percent versus 41 percent) than patients in the auto group.

These patients also had a higher progression-free survival rate (35 percent versus 18 percent) and overall survival rate (65 percent versus 58 percent) than patients in the auto group.

Furthermore, patients in the auto-allo group who received their donor transplant had higher complete response (56 percent versus 44 percent), progression-free survival (39 percent versus 19 percent), and overall survival (63 percent versus 60 percent) rates compared to patients in the auto group who received two autologous stem cell transplants.

“[These results] were not very surprising, since donor stem cell transplantation has an immunological effect against cancer that is not present in autologous stem cell transplantation,” commented Dr. Gahrton.

In addition, both patients with del(13q14) and patients without del(13q14) achieved better outcomes in the auto-allo group than in the auto group.

Overall, 31 percent of patients who received a “mini” donor transplant developed acute GVHD, which occurs within 100 days of transplantation, and 54 percent developed chronic GVHD, which occurs at least 100 days after transplantation.

Both Dr. Gahrton and Dr. Vij recommended longer follow-up studies investigating the role of donor stem cell transplantation for myeloma patients.

“Further studies should include novel drugs like [Velcade ^[5]] bortezomib before or after [“mini” donor stem cell] transplantation, since this may further improve the treatment outcome for myeloma patients,” added Dr. Gahrton.

For more information, please see the article in the Journal of Clinical Oncology ^[6] (abstract).