Six-Year Follow-Up of Lenalidomide for Multiple Myeloma

Chicago—After 6 years of follow-up in a phase 2 trial, researchers found that a combination therapy of dexamethasone, lenalidomide, and clarithromycin remained an effective regimen for patients who were newly diagnosed with multiple myeloma. Adriana Rossi, MD, Weill Cornell Medical College and New York Presbyterian Hospital, the study’s lead author, presented the results in an oral abstract session at the ASCO meeting. Dr. Rossi said researchers were interested in studying the incidence of second primary malignancies in transplant-eligible patients who received lenalidomide as front-line treatment for multiple myeloma. They included 72 patients (57% males) who were required to have a minimum of 5 years of no evidence of disease at the time of enrollment. The median age was 63 years, and 54% of patients had advanced disease as measured by the International Staging System for multiple myeloma. Prior to enrollment, the researchers identified 11 prior malignancies in 10 patients. Patients received once-weekly 40-mg doses of dexamethasone, 25-mg daily doses of lenalidomide on days 1 through 21 of a 28-day regimen, and 500-mg twice-daily doses of clarithromycin for each of the 28 days. They continued treatment until they had disease progression, stem cell transplantation, or intolerable adverse effects. Dr. Rossi said initial results indicated the regimen was effective with an overall response rate of 90%. In addition, 53% of patients had a complete response or near-complete response, 21% had a very good partial response, and 17% had partial response. Furthermore, the 2-year event-free survival rate was 97.2%. The results presented at the ASCO meeting included a prospective follow-up for all patients and a retrospective review for second primary malignancies. As of February 1, 2011, 68 of the 72 patients were available for evaluation. Of the 68 patients, 33 received autologous stem cell transplantation (ASCT), 34 received continuous lenalidomide, and 1 died. Of the patients who underwent ASCT, 6 progressed and remained on second-line therapy, 7 died, and 20 responded and remained under observation. In the continuous lenalidomide group, 14 progressed and remained on second-line therapy, 9 died, and 11 remained on the study drug. The median progression-free survival was 47.8 months, with a 5-year progression-free survival rate of 54.5%. The 4-year overall survival rate was 82.2%, while the 5-year overall survival rate had not been reached. Dr. Rossi said progression-free survival was not significantly different for patients who continued to receive lenalidomide compared with those who underwent a transplant. The 5-year progression-free survival rate was 60.7% in the no-transplant group compared with 48.0% in the transplant group (P=.61). The authors observed 5 second primary malignancies. All were solid tumors and none were hematologic malignancies. The median time to diagnosis was 31.2 months and ranged from 8 to 53 months. They also observed 6 cases of noninvasive skin cancer, of which 4 were basal cell carcinoma and 2 were squamous cell carcinoma. The median time to diagnosis was 34 months and ranged from 5 to 64 months. The authors also attempted to identify potential risk factors for which patients would have second primary malignancies. They found that second primary malignancies were not associated with specific multiple myeloma chromosomal abnormality, prior history of malignancy, ASCT status, whether the patients were receiving lenalidomide, or sex. In addition, they analyzed the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) database from 2003 to 2007 and found the overall incidence rate of invasive cancer for people ≥65 years of age was 2.1 per 100 patient-years. They then adjusted their data (175.7 person-years of follow-up) and found an incidence rate of 2.85 per 100 patient-years, which Dr. Rossi said was not significantly different from the SEER data. Dr. Rossi said the study’s limitations included its small cohort size and retrospective review design, as well as that the authors did not perform bone marrow surveillance on patients to determine the development of myelodysplastic syndromes.