Results of a recent analysis suggest that newly diagnosed multiple myeloma patients receiving Revlimid or thalidomide as initial therapy have similar prognoses regardless of whether they receive an early stem cell transplant or delay the transplant and continue their initial treatment.

Specifically, the authors of the analysis found that myeloma patients who received a stem cell transplant early in the course of their disease had a comparable survival rate and time to disease progression as patients who continued Revlimid (lenalidomide) or thalidomide (Thalomid) as initial therapy and intended to do the transplant later.

Based on these findings, the researchers conclude that patients receiving Revlimid or thalidomide as initial therapy should have the option of continuing the treatment and delaying the stem cell transplant if they wish to do so.

“There are no definitive recommendations [for which patients should receive an early transplant]. This depends on side effects they are having with the treatment, patient preference, age, etc. It is a decision that the physician and patient need to make depending on the goals,” Dr. Shaji Kumar of the Mayo Clinic in Rochester, Minnesota, told The Beacon.  Dr. Kumar is the lead author of the current study.

The authors of the study acknowledge, however, that their analysis was retrospective in nature and therefore did not allow for a comparison of quality of life between patients receiving early and delayed transplants. Thus, they recommend prospective trials comparing early and delayed transplants to explore whether these two approaches give patients a similar quality of life.

“Quality of life is important because patients who delay transplant are on continued therapy for long periods of time and may have side effects related to the therapy,” said Dr. Kumar.

Dr. Gary Schiller of the Ronald Reagan UCLA Medical Center in Los Angeles, who was not involved in the study, agreed that information about patients’ quality of life is important in evaluating early versus delayed stem cell transplants.

“[Because the study is retrospective, it lacks] a quality of life instrument, [and] one doesn’t know how well the late transplant was tolerated. One may also suspect that patients eligible for late transplant may never have reached transplant due to toxicity, early death, lack of response, or organ toxicity,” said Dr. Schiller.

Despite the current study's findings, Dr. Schiller said he "would continue to consolidate remissions with stem cell transplant early, when it is well-tolerated, nearly uniformly successful, and easily feasible for most patients with intermediate to advanced stage myeloma up to age 75.”

In recent decades, novel agents such as thalidomide, Revlimid, and Velcade have improved overall survival and treatment outcomes in myeloma patients.

According to the study authors, the high response rates and high tolerability associated with these therapies have led myeloma patients to increasingly choose to delay stem cell transplantation, the current standard of treatment for myeloma patients below 65 years of age.

Previous studies have suggested that early and delayed stem cell transplants have similar efficacies in myeloma patients receiving steroid-based therapies or alkylating agents, a type of chemotherapy that prevents DNA replication in cancer cells.

It is unclear, however, whether early and delayed transplants also have similar efficacies in patients receiving treatment with novel agents.

To investigate this issue, researchers retrospectively assessed the outcomes of 290 newly diagnosed multiple myeloma patients who received either Revlimid or thalidomide as initial therapy.  All patients attended the Mayo Clinic at least once in the period from 2001 to 2008.

Initial therapy consisted of thalidomide plus dexamethasone (Decadron) in 42 percent of patients and Revlimid plus dexamethasone in 58 percent of patients.

Patients who received a stem cell transplant within 12 months of diagnosis and within two months of stem cell collection were placed into the early transplant group (61 percent). Early transplant patients had a median age of 58 years. They received a stem cell transplant a median of five months after diagnosis. Prior to the transplant, they had received initial therapy for a median of four months, which consisted of thalidomide plus dexamethasone in 51 percent of patients and Revlimid plus dexamethasone in 49 percent of patients.

Patients who continued initial therapy were placed into the delayed transplant group (39 percent). This group included patients who received a delayed transplant as well as patients who continued initial therapy and did not receive a transplant. Patients in this group had a median age of 61 years. They received a stem cell transplant a median of 45 months after diagnosis. Prior to the transplant, patients in the delayed transplant group had received initial therapy for a median of nine months, which consisted of thalidomide plus dexamethasone in 67 percent of patients and Revlimid plus dexamethasone in 33 percent of patients.

The median follow-up time was 40 months and 34 months from diagnosis for patients in the early and delayed transplant groups, respectively.

At the median follow-up time, all early transplant patients had received a stem cell transplant, compared to 38 percent of patients in the delayed transplant group.

The researchers found that the survival rate four years after diagnosis was similar between patients in the early and delayed transplant groups (72.7 percent versus 73.4 percent).

The survival rate four years after diagnosis was higher for both patients in the early and delayed transplant groups who received Revlimid (82 percent and 86 percent, respectively) as initial therapy compared to patients in both groups who had received thalidomide (68 percent and 64 percent).

The time to disease progression after stem cell transplantation was also similar between patients in the early and delayed transplant groups (20 months versus 16 months).

When the researchers compared the outcomes of patients in both groups who had received a transplant, they found that patients in the early transplant group had similar response rates and time to disease progression than the patients in the delayed transplant group who had received a transplant by the follow-up time.

Of the early transplant patients, 92 percent responded to treatment, with 35 percent achieving a complete response, compared to an 87 percent response rate among patients who received a delayed stem cell transplant, with 37 percent achieving a complete response.

The time to disease progression after the transplant was 19.7 months for patients who received an early transplant, compared to 18 months for patients who received a delayed transplant.

However, early transplant patients had a better four-year overall survival rate than patients who received a delayed transplant (66 percent versus 56 percent).

Twenty-two percent of patients had died at the median follow-up time, mainly because of disease progression.

For more information, please see the article in the journal Cancer (abstract).