Chicago, IL—The topic of multiple myeloma was addressed in many presentations at the 2013 Annual Meeting of the American Society of Clinical Oncology. The following is a brief description of some of the key presentation related to this disease state.
Myeloma Drugs Are Often Prescribed Off Label
Off-label prescribing is common among Medicare beneficiaries with advanced cancer, and not all off-label use is consistent with compendium recommendations by the National Comprehensive Cancer Network (NCCN). Among the tumor types, myeloma appears to be the tumor in which drugs are most likely to be used off label, according to Dawn L. Hershman, MD, MS, Associate Professor of Medicine, Division of Medical Oncology, Columbia University Medical Center, New York.
In a retrospective analysis of the Surveillance, Epidemiology and End Results–Medicare database of more than 42,000 patients (1998-2008), 45% had received a drug that was not approved by the US Food and Drug Administration; although most of this off-label use was endorsed by the NCCN compendia, 30% was not. Myeloma was the cancer associated with the most (80%) off-label drug use and the highest proportion (75%) of treatments not endorsed by NCCN compendia, Dr Hershman said. She suggested that the high use of off-label treatments reflects the growing list of drugs that are demonstrating strong efficacy in phase 2 trials of patients with myeloma.
Prolonged Survival Predicted by Deep Sequencing
Multiparameter flow cytometry and deep sequencing of genes were able to accurately identify patients who had minimal residual disease (MRD) after treatment, a factor that predicted longer survival time than a complete response to treatment, according to traditional response criteria in myeloma, Spanish investigators reported.
To detect MRD, the investigators used a genetic sequencing–based method that identified clonal rearrangements of immunoglobulin genes in diagnostic samples from patients in the Spanish Myeloma Group trials. They also looked for MRD by the more conventional flow cytometry and found that of 46 samples, only 3 were discordant between the assays for the presence of MRD. With both tests, MRD negativity was associated with significantly improved progression-free survival (PFS) compared with patients not achieving MRD status. When researchers analyzed patients achieving a conventional complete response, PFS and overall survival (OS) were improved only in the patients who were negative for MRD using sequencing compared with patients who still have MRD despite a complete response, reported Joaquín Martínez-López, MD, PhD, of the Servicio de Hemotología, Hospital Universitario 12 de Octubre, Madrid, Spain.
“MRD assessment by sequencing is a useful method for patient risk stratification and can be used to determine molecular complete response in multiple myeloma,” Dr Martínez-López suggested.
Daratumumab Showing Promise
A phase 1/2 study evaluated the investigational monoclonal antibody daratumumab, which—like elotuzumab and siltuximab—harnesses the immune system to attack myeloma cells. The phase 1 portion of the trial included 32 patients with relapsed or refractory multiple myeloma who had received a median of 6 previous lines of therapy. Of 12 patients receiving ≥4 mg/kg of daratumumab, 42% responded and another 25% achieved a minor response. After a median follow-up of 18.4 weeks, the median PFS for this subset of patients has not yet been reached, reported Henk M. Lokhorst, MD, PhD, from the Department of Hematology, University Medical Center Utrecht, the Netherlands.
Infusion-related side effects occurred in 44% of patients. Phase 2 of the trial has enrolled 7 patients to date, who are receiving the maximum tolerated dose (MTD) of 8 mg/kg of daratumumab. Saad Zafar Usmani, MD, Director of Developmental Therapeutics, Myeloma Institute for Research and Therapy, University of Arkansas for Medical Science, Little Rock, commented that the results are encouraging for such a refractory population.
Carfilzomib plus Melphalan
French investigators reported the results of a phase 1/2 study of carfilzomib (Kyprolis) given in combination with melphalan (Alkeran) and prednisone in newly diagnosed patients with myeloma aged >65 years (median age, 72 years). The phase 1 dose-escalating study of 24 patients established the MTD at 36 mg/m2. Phase 2 involved 44 additional elderly patients who received 36 mg/m2 of carfilzomib in combination with melphalan and prednisone.
After a median follow-up of 12 months, the median PFS was 22 months, and the estimated 2-year OS rate was 87%. Overall, 11% of patients discontinued treatment as a result of side effects. Although most were predictable, 43% of patients experienced heart-related complications and 6% had moderate-to-severe neuropathy, reported Cyrille Touzeau, MD, from the Service d’Hématologie, Hôpital Hôtel-Dieu, Centre Hospitalier Universitaire de Nantes, France.
Dr Usmani commented that he was encouraged by the high response rates achieved with this combination, but he was concerned about the cardiac side effects, especially because comorbid heart disease is common in elderly patients.