View Full Version : ECCO-ESMO: Stem Cell Therapy Still Multiple Myeloma Mainstay

09-28-2011, 01:07 PM
By Ed Susman, Contributing Writer, MedPage Today
Published: September 27, 2011
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and
Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner

STOCKHOLM -- Although new drugs have proven effective in multiple myeloma, results of a phase III study confirmed that autologous stem cell transplantation remains a therapeutic bedrock for newly diagnosed disease, researchers found.

Progression-free survival after 26 months was achieved by 73% of patients who received autologous stem cell support plus melphalan, compared with only 54% of patients who were treated with lenalidomide (Revlimid) plus melphalan and prednisone (P=0.0002), said Federica Cavallo, PhD, of the University of Turin in Italy.

The difference translates to a relative risk reduction of 49% for those patients receiving stem cells, she reported at the European Multidisciplinary Cancer Congress, formerly known as the joint Congress of the European Cancer Organization and the European Society for Medical Oncology. Action Points
Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

Explain that although new drugs have proven effective in multiple myeloma, results of a phase III study confirmed that autologous stem cell transplantation remains a therapeutic bedrock for newly diagnosed disease.

Note that in a comparison of treatment with lenalidomide (Revlimid) plus melphalan and prednisone, with high-dose melphalan plus autologous stem cell support, progression-free survival after 26 months was achieved in 73% of patients who received melphalan plus stem cell support compared with 54% who received only drugs.
"In this prospective trial, we tried to answer the question as to whether, in younger patients with multiple myeloma, autologous stem cell transplantation is still an option in the era of novel agents," she explained in her oral presentation.

Cavallo noted that the introduction of drugs such as thalidomide has improved outcomes in response rates and in survival. The results appeared to be as good as those achieved with stem cell transplantation, in at least one meta-analysis, she said.

The researchers focused on using novels agents, such as lenalidomide, in younger patients (<65 years; average age 58) and comparing induction based on lenalidomide followed by either transplantation or continued therapy with novel agents.

"As expected, we did see less grade 3 to 4 toxicity with the melphalan-prednisone-lenalidomide arm," Cavallo said. For instance, grade 3 to 4 gastrointestinal toxicity was 0% for the drug arm versus 21% in the transplant arms (P<0.001). "However, the dropout rate between the groups was comparable," she added.

She also noted that 20% of the drug therapy group achieved a complete remission from the disease while 25% of the autologous stem cell transplant patients achieved a complete remission (P=0.55). The 18-month overall survival (OS) was similar in both arms of the trial: 91% in the drug therapy treatment and 95% in the transplant group (P=0.073).

"A longer follow up is needed to assess OS," Cavallo said. She noted that some patients who progressed could opt to receive stem cell transplants and that could skew survival results.

She added that there were no differences in early deaths in the study that enrolled 402 patients, 202 of whom were treated with the drug therapy and 200 of whom were randomized to the transplant group.

In the trial, symptomatic patients underwent induction therapy with lenalidomide (25 mg a day) for days one through 21 and low-dose dexamethasone (40 mg) on days one, eight, 15, and 22 of a 28-day cycle. There were four induction-phase cycles. All patients were also given cyclophosphamide to mobilize stem cells.

After completion of the induction phase, patients were then randomly assigned to either the drug therapy treatment arm or the transplant arm, Cavallo said. The treatment protocols were:

Drug arm: Six, 28-day cycles of 0.18 mg/kg of melphalan on days one through four; prednisone 2 mg/kg on days one through four and lenalidomide 10 mg on days through 21.
Transplant arm: Tandem melphalan (200 mg/m2) with stem cell support.
About 91% of the patients in both arms were able to produce enough stem cells to allow them to be in the transplant arm, or to have cells available if they later needed a transplant.

Cavallo speculated that the high dose of melphalan used in the transplant group might have produced profound cytoreduction that translated into longer disease-free survival.

Genetic abnormalities that could impact outcomes were comparable between the two arms of the study, Cavallo said.

"While many of these drugs are helpful in the treatment of multiple myeloma, we still see the need for autologous stem cell transplantation," commented Iryna Titorenko, MD, a medical oncologist with the National Cancer Institute of Ukraine in Kyiv. She did not participate in Cavallo's trial.

"We are always looking for better treatments because transplantation sometimes fails too," Titorenko told MedPage Today.

Cavallo had no disclosures.

Titorenko had no disclosures.

Lead author Antonio Palumbo of the University of Torino has disclosed commercial interests with Janssen-Cilag and Celgene.

Primary source: European Journal of Cancer
Source reference:
Palumbo A, et al "A phase 3 study comparing melphalan-prednisone-lenalidomide with high-dose melphalan and autologous transplantation in newly diagnosed patients with multiple myeloma" Eur J Cancer 2011; Abstract 9200: pS639.