Follow-up results from a long-term study conducted in Italy indicate that quality of response may be the most significant predictor of long-term survival in newly diagnosed multiple myeloma patients receiving a stem cell transplant.

The results also showed that hemoglobin levels and platelet counts at diagnosis were independent factors predicting for long-term survival.

“[This study] confirms the importance of achieving high-quality responses not only as a surrogate marker of progression-free survival and overall survival but also for long-term overall survival,” said Dr. Elena Zamagni, one of study’s investigators from Seragnoli Institute of Hematology in Bologna, Italy.

However, Dr. Angela Dispenzieri from the Mayo Clinic, who was not involved in the study, pointed out that patients in this study who received a double stem cell transplant achieved a higher complete response rate but did not have significantly longer overall survival compared to patients who received a single transplant.

Her theory is that achieving a complete response is largely a prognostic factor that indicates which patients have a less aggressive form of myeloma.

According to Dr. Dispenzieri, there are two major factors affecting the number of long-term survivors in a clinical trial: the patient mix in the study, and the number of available effective therapies, not just at diagnosis but also in later stages of the disease.

Dr. Dispenzieri explained that there have always been long-term survivors among patients with multiple myeloma, but the number has clearly increased since the introduction of the so-called novel myeloma therapies, thalidomide ^[1] (Thalomid), Velcade ^[2] (bortezomib), and Revlimid ^[3] (lenalidomide).

Nevertheless Dr. Dispenzieri stated the major take home message of the Italian analysis is that “Patients are doing better all the time, and there is reason for lots of hope among patients and doctors.”

Findings from the Italian study were presented earlier this month at the 17th annual meeting of the European Hematology Association (EHA) in Amsterdam.

The analysis was based on a clinical trial in which 321 newly diagnosed myeloma patients were randomly assigned to receive either a single or double stem cell transplant between January 1996 and December 2001.

Patients who received a single stem cell transplant received a preparative regimen consisting of 200 mg/m² of melphalan ^[4] (Alkeran). Those who received a double stem cell transplant received a preparative regimen consisting of 200 mg/m² of melphalan followed three to six months later by 120 mg/m² of melphalan and 12 mg/kg of busulfan ^[5].

The initial results after a median follow-up time of 55 months showed that patients who received a double stem cell transplant achieved higher complete response rates and a longer progression-free survival time than patients who received a single stem cell transplant. However, overall survival was comparable between patients who received a single and double stem cell transplant.

The current analysis aimed to investigate the long-term outcomes of these patients and to identify factors that contribute to long-term survival.

After ten years from the start of treatment, 23 percent of patients were alive. These patients were classified as long-term survivors; 25 percent of long-term survivors also remained disease-free after ten years.

Statistical analysis showed that best response following stem cell transplantation was the most important factor predicting progression-free survival in these patients.

Hemoglobin levels above 10 g/dl and platelet counts above 150,000/mmc at diagnosis were also independent factors predicting for long-term survival.

The researchers found that 47 percent of patients who received a double stem cell transplant and 33 percent of patients who received a single stem cell transplant achieved a complete response or near complete response after transplantation.

The median duration of response among those who achieved a complete response or near complete response was 70 months among long-term survivors, compared to 21 months in the remaining population.

The progression-free survival time was 74 months for long-term survivors, compared to 25 months for the remaining population.

After a median follow-up of 61 months for all patients and 120 months for long-term survivors, patients who received a double stem cell transplant had a longer time to disease progression (41 months versus 25 months) and progression-free survival (37 months versus 25 months) than patients who received a single stem cell transplant.

However, the overall survival remained statistically indistinguishable between patients who received a double versus single stem cell transplant (71 months versus 67 months, respectively).

According to Dr. Dispenzieri, one reason the survival rates may be similar in the two patient groups is that many patients in the single-transplant group went on to receive a second transplant as salvage therapy.

“I suspect the key to superior outcomes with current drugs and modalities lies not in a magical sequence or combination, but in the availability of more and more useful treatments,” she explained.

For more information, please see the abstract 0299 ^[6] on the EHA meeting ^[7] website. For more information on the underlying study, please see the Journal of Clinical Oncology ^[8].