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Donor Stem Cell Transplant Offers No Comparative Benefit As Second Transplant In Multiple Myeloma Patients (ASH 2010)

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Published: Dec 6, 2010 7:08 pm

Interim results of a Phase 3 trial show no statistically significant differ­ences in relapse and overall survival rates between multiple myeloma patients who received a donor stem cell transplant as their second transplant compared to patients receiving two sequential transplants with their own stem cells.

Patients who received a donor transplant had an increased risk of death and other serious side effects, which outweighed the therapeutic benefits of the procedure.

The results of the trial were presented yesterday by Dr. Amrita Krishnan from the City of Hope Cancer Center in Duarte, California, at the American Society of Hematology’s 2010 annual meeting in Orlando.

“We did see evidence of the graft-versus-myeloma effect [a benefit associated with donor transplants] with a 60 percent reduction in the risk of disease progression,” explained Dr. Krishnan. “However, that was not enough to offset the transplant-related mortality, which, at 12 percent, was low in our study, but still enough to overcome the benefits of a [donor] transplant.”

Dr. Krishnan suggested further research be conducted to reduce the transplant-related death rate in order to gain the benefits of the donor transplant approach without the associated risks.

The findings generated discussion in the audience as to whether or not donor transplants should continue to be used in multiple myeloma.

There was a consensus in the audience that donor stem cell transplantation should be limited to clinical trial settings for multiple myeloma patients with standard-risk disease.

Dr. Krishnan pointed out that it is too early to tell if donor transplants are broadly inappropriate for myeloma patients. She believed they still need to be considered for high-risk patients. She added that longer follow-up studies are necessary to determine the long-term outcome of donor transplants.

Research has shown that multiple myeloma patients who undergo a stem cell transplant using their own stem cells have improved overall survival outcomes. In the procedure, the patient’s own stem cells are collected prior to receiving high-dose chemotherapy, which often destroys both healthy and cancerous cells. This procedure is known as autologous stem cell transplantation. Following chemotherapy, the patient receives an infusion of the previously collected stem cells, which will mature to replace the destroyed cells.

In some cases, patients may receive two sequential transplants, which is called tandem transplantation. Research has indicated that tandem transplantation generally results in superior overall survival outcomes compared to single transplantation.

Although it is not a common procedure, myeloma patients may also receive a transplant with stem cells from a matched donor (often a sibling). This procedure is known as allogeneic stem cell transplantation. Allogeneic transplants are currently the only treatment that has the potential to completely eliminate all myeloma cells from a patient's body.

Although past studies have indicated that allogeneic transplantation following high-dose chemotherapy is associated with a high rate of death and side effects, there have been promising results for pairing allogeneic transplantation with reduced-intensity chemotherapy.

Based on promising preliminary results, researchers from the Blood and Marrow Transplant Clinical Trials Network conducted a study to determine if autologous stem cell transplantation followed by reduced-intensity allogeneic transplantation is more effective than tandem autologous transplantation.

The researchers assigned 710 multiple myeloma patients to one of two treatment arms: auto-auto or auto-allo. Patients were enrolled in the auto-auto arm if they did not have a matched sibling stem cell donor.

Of the 710 patients in the study, 625 were categorized as standard-risk.

The auto-auto treatment group underwent tandem autologous stem cell transplantation with 200 mg/m2 of melphalan (Alkeran)-based chemotherapy. Patients were also randomly assigned to receive maintenance therapy of thalidomide (Thalomid) and dexamethasone (Decadron) or observation for one year.

Patients in the auto-allo arm underwent autologous stem cell transplantation with 200 mg/m2 of melphalan-based chemotherapy. Patients then received total body irradiation, followed by allogeneic stem cell transplantation using the stem cells from a matched sibling donor.

After three years, progression-free survival was 46 percent for patients receiving auto-auto transplants, compared to 43 percent for the patients receiving auto-allo transplants. Similarly, overall survival was 80 percent and 77 percent for the two groups, respectively.

In the auto-auto arm, 50 percent of patients relapsed, compared to 46 percent of patients in the auto-allo arm. However, 11 percent of patients in the auto-allo arm died due to treatment-related causes, compared to 4 percent of auto-auto patients.

Researchers also found that the progression-free survival and overall survival were comparable between patients in the auto-auto arm who received maintenance therapy and those who did not. Dr. Krishnan explained that this might be attributed to the fact that 84 percent of patients did not complete the maintenance therapy due to poor tolerability of the regimen. She added that new maintenance regimens including Revlimid (lenalidomide) are being studied for use after donor transplantation.

For more information, please refer to abstract 41 on the American Society of Hematology annual meeting website.

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  • Lynda Clark said:

    I was part of this trial, one of the auto/auto participants (my sibling wasn't a match). Had to stop the maintenance regimen early, but still doing great, no recurrence, still in remission. I consider being part of a clinical trial good for me and other patients.

  • Lori Puente said:

    I was unhappy to read that some in the audience were calling for a stop to allo transplants for MM based on this study, one study. The Baby out With the Bathwater routine. There are patients with Multiple Myeloma where it is their last and only hope of pulling this thing out of the fire. For them the typically 30%+ morbidity associated is a completely reasonable odd to consider this option, because if they don't they will 100% die. Leukemia patients, same thing.

    In the long run, I really hope we can find something less invasive. I feel that way about many of the cancers we see in the western world.

    Great reporting, again, TMB!