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Should high-dose chemo/transplant still be considered first-line therapy in myeloma?

Should high-dose chemo/transplant still be considered first-line therapy in myeloma?

ABSTRACT: Advanced autologous stem cell transplant techniques and high-dose chemotherapy vie to meet the goal of prolonged disease control.

With the availability of newer drugs for treating multiple myeloma, such as proteosome inhibitors and immunomodulatory drugs (IMiDs), outcomes and depth of response are steadily improving. These developments have led to a debate about whether high-dose chemotherapy and autologous stem cell transplant should still be considered first-line therapy or whether newer drug regimens should replace transplant.

Oncology News International spoke with two myeloma experts: Donna Reece, MD, argued that transplant should not be abandoned as first-line therapy, while Morie Gertz, MD, posited that a drug regimen offers the advantage of long-term disease suppression.

Transplant: Not a barbaric procedure
“I don’t believe we have sufficient data yet to support abandoning transplant,” said Dr. Reece, who is director of the Program for Multiple Myeloma and Related Disorders at Princess Margaret Hospital in Toronto. “The new drugs are clearly more exciting than the older drugs in our armamentarium, but we do not yet have complete data on median time to progression and survival with these newer agents. Perhaps in the future, we will have enough information to justify this paradigm shift, but that is not the case at present.”

The goal of management for multiple myeloma is the achievement of prolonged periods of disease control with a good quality of life by the judicious use of sequential treatment regimens, she said. “The goal has realistically never been cure in most centers,” she added.

Outcomes are improving with both new transplant techniques and newer drug-only regimens. With older transplant techniques, median progression-free survival (PFS) is 2.5 to three years, and appears to be longer in more recent studies, she said. “We don’t know the progression-free survival with newer drug-only combinations, such as Revlimid/dexamethasone (RD) or Revlimid/bortezomib/dexamethasone (RVD),” she emphasized (see Table).

The ECOG E4A01 trial compared lenalidomide plus high-dose dexamethasone with lenalidomide plus low-dose weekly dexamethasone. The high-dose arm was much more toxic than the low-dose arm, and median time to progression for both groups was about two years (ASCO 2008 abstract 8504).

“Some of these patients went on to transplant, so this trial does not tell us about the true time to progression with Revlimid/dexamethasone. To make a decision to abandon transplant as part of initial therapy, I would need those data,” she emphasized.

A separate retrospective analysis of 100 patients treated with lenalidomide/dexamethasone at the Mayo Clinic in Rochester, Minn., reported a median time to progression of 31 months (Blood online, March 26, 2009).

Median time-to-progression is similar for older transplant studies and for studies of newer drug-only regimens: 2.5 to three years for transplant and 31 months with lenalidomide/dexamethasone. However, cost is an issue. One autologous stem cell transplant is about half the cost of one year of Revlimid therapy: transplant costs about $44,000, while the cost of one year of treatment with Revlimid is about $112,000 in Canada, Dr. Reece said.

“Some people say that taking pills is easy while transplant is associated with a great deal of morbidity. Transplant is not that bad. Patients have a definite period of fatigue, but it is hardly a barbaric procedure. Mortality in our center is approximately 1.5%, and some patients clearly achieve remissions which last for seven or eight years,” she said.

Since achieving remission is almost universal with modern treatment, the availability of effective salvage therapies is another important consideration in selecting first-line therapy. While there are ample data on the use of lenalidomide/dexamethasone as salvage therapy after transplant, there are no data on salvage strategies after first-line stem cell transplant or after first-line lenalidomide/dexamethasone or other newer combination therapies such as RVD.

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