June 3, 2013

MMRF Newsflash from ASCO 2013 - Volume 2

Welcome to our second day of on-site coverage of the 2013 American Society of Clinical Oncology (ASCO) Annual meeting.

Today’s oral presentations featured results from studies in both patients with newly diagnosed and relapsed refractory disease.

Dr. Palumbo from Università di Torino presented final results from a study of 402 patients

1) How does the combination of Revlimid (lenalidomide) and melphalan-prednisone (MPR) compare to autologous stem cell transplantation?
2) What is the role of maintenance therapy with Revlimid following either MPR or stem cell transplantation?

  • Results of this study showed that time without disease progression (progression-free survival) was extended in patients undergoing transplantation as compared with MPR.
  • Maintenance therapy with Revlimid significantly reduced the risk of disease progression and extended survival time.
  • Patients who had the best outcomes were those who received a stem cell transplant followed by maintenance therapy with Revlimid.

Dr. Palumbo also addressed the risk of developing a second cancer in patients treated with Revlimid in an analysis of 7 clinical studies with 6383 patients.

  • The results of the study confirmed earlier findings and indicated that there is a small increased risk of a second cancer that is primarily associated with the combination of oral melphalan and Revlimid. These cancers included only hematologic cancers (those related to the blood) such as acute leukemia and myelodysplastic syndrome (MDS) and not any solid tumors.
  • Despite this risk, the overall survival benefits far outweighed the small risk of a second cancer.

Dr. Martinez-Lopez from the Hospital Universitario 12 de Octubre presented data illustrating the value of achieving minimal residual disease in newly diagnosed patients versus those with relapsed/refractory disease.

  • He concluded that the depth of response (i.e. CR) and achievement of minimal residual disease predicts for longer time without disease progression and increased survival in newly diagnosed patients.
  • In contrast, any response to treatment in relapsed/refractory disease can lead to improved survival—even minor responses or stable disease.

Data from SWOG, a major cancer study group, looking at risk factors for progression from MGUS and asymptomatic myeloma to active myeloma, was presented by Dr. Dhodapkar from Yale University.

  • Factors associated with progression to active myeloma included an increased genetic expression profile risk score, the degree of M protein spike, and the level of monoclonal free light chains. The greater the number of risk factors present, the more likely the progression to myeloma.
  • Dr. Kaufman from Emory University, in a discussion of these data, noted that even among patients with these risk factors 25% do not progress. Thus, we still do not have sufficient information to determine which patients with asymptomatic disease need to be treated.

Dr. Weisel, presenting on behalf of Dr. San Miguel from Hospital Universitario de Salamanca, provided an update on the results of the phase III trial which compared the combination of Pomalyst (pomalidomide) and low-dose dexamethasone to high dose dexamethasone in 455 patients with relapsed and refractory myeloma. These patients were “double refractory”, ie, they had failed both Velcade (bortezomib) and Revlimid.

  • Results confirmed earlier reported findings and showed significantly increased response rates, a significant improvement in time without disease progression (4 months with Pomalyst-low dose dexamethasone versus 1.9 months with high-dose dexamethasone) as well as increased survival time (12.7 months with Pomalyst-low dose dexamethasone versus 8.1 months with high-dose dexamethasone).
  • Side effects were manageable with the most common serious side effects being low white cell blood counts.

There were also presentations on two new agents, daratumumab and ixazomib, as well as a new combination of myeloma drugs for patients with relapsed/refractory myeloma.

  • Dr. Lokhorst from University Medical Center presented results from a Phase I/II trial with a monoclonal antibody, daratumumab, in relapsed/refractory myeloma. In this early study 75% of patients were refractory to both Velcade and Revlimid. 31% of patients responded, which is similar to what has been reported with recently approved agents, Pomalyst and Kyprolis, in this patient population which is promising as side effects were minimal and dexamethasone was not part of the treatment regimen.
  • Dr. Kumar from the Mayo Clinic presented data from a Phase I study with weekly ixazomib, an oral proteasome inhibitor in the same class as Velcade and Kyprolis (carfilzomib) in relapsed/refractory myeloma patients who progressed after an average of 4 therapies. 26% of patients responded at the dose level that was established. Serious side effects included diarrhea, pneumonia, vomiting, increased creatinine levels (a measure of kidney function), hypercalcemia (increased calcium levels), nausea and fever. Phase III trials evaluating this ixazomib and Revlimid (lenalidomide)-dexamethasone are underway in both relapsed/refractory patients and newly diagnosed patients.

Look for our next posting on the multiple myeloma poster session!