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Delaying Transplant after Immunomodulatory Therapy Does Not Worsen Outcomes

Value-Based Care in Myeloma - Transplant Considerations, Multiple Myeloma
Caroline Helwick

Results of a recent study suggest that delaying autologous stem-cell transplantation (ASCT) after immunomodulatory therapy is effective and leads to comparable survival rates as with early transplantation in patients with multiple myeloma (Kumar SK, et al. Cancer. 2012;118:1585-1592). The study results indicate that survival outcomes are not compromised when ASCT is delayed if stem cells are harvested early; however, the study was not randomized and was conducted before the bortezomib era.

Shaji Kumar, MD, Associate Professor of Medicine, Hematology Division, Mayo Clinic, Rochester, MN, led the study of 290 patients with untreated myeloma. “With the increasing tolerability and efficacy of upfront treatments, ASCT continues to be used later in the course of the disease. Prior to the new drugs becoming available, a French randomized trial had shown that a delayed transplant at the time of first relapse is equivalent to an early transplant in terms of overall survival (OS) but is inferior with respect to quality of life. We do not know if this holds true for the current era. Our retrospective experience suggests that it does,” Dr Kumar told Value-Based Care in Myeloma.

Study Details

Patients received immunomodulatory drug (IMiD)-based initial therapy, including 123 patients who received thalidomide/dexamethasone (TD) and 167 who received lenalidomide/dexamethasone (LD) induction before ASCT. Patients who underwent a stem-cell harvest attempt were considered eligible for a transplant and were included.

Individuals who underwent ASCT within 12 months of diagnosis and within 2 months of harvest were considered to have an “early” transplant (N = 173; 60%), whereas those who received ASCT more than 12 months after diagnosis were considered to have a delayed ASCT (N = 112; 40%). At the time of the analysis, 42 patients in the delayed group had undergone ASCT.

Median time to transplant was 5.3 months for the early ASCT group and 44.5 months for the delayed ASCT group. Patients in the delayed ASCT group did not have a less favorable outcome, Dr Kumar and his colleagues reported.

Excellent 4-Year Survival, Regardless of Timing

The 4-year OS rate from the time of diagnosis was 73% in both groups and was comparable, regardless of what induction regimen was received. Patients who received TD had a 4-year OS rate of 68% with early ASCT and a rate of 64% with delayed ASCT; those who received LD had an 82% OS rate at 4 years when transplanted early and 86% with delayed ASCT.

The times to progression after ASCT were also similar between the early and delayed approaches: 20 months and 16 months, respectively, which were not significantly different.

“The current results indicated that, in transplantation-eligible patients who receive IMiDs as initial therapy followed by early stem-cell mobilization, delayed ASCT results in similar OS compared with early ASCT. It is noteworthy that an excellent 4-year survival rate of >80% was observed among transplantation-eligible patients who received initial therapy with LD, regardless of the timing of transplantation,” according to Dr Kumar and colleagues.

Dr Kumar added a few caveats in an interview. “The overall survival appears to be equivalent for both approaches; however, this assumes that transplant as a treatment for relapsed myeloma is considered early in the relapsed disease, that is, prior to too many other treatments for relapsed disease. Also, this study is retrospective; hence, there might be some biases. Moreover, we do not have quality-of-life data,” he noted. “The definitive answer will come from the ongoing clinical trials.”

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Last modified: May 20, 2015
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