Lenalidomide is an immunomodulatory drug and a structural analogue of thalidomide which has been developed by Celgene. REVLIMID (lenalidomide) in combination with dexamethasone is indicated for the treatment of patients with multiple myeloma (MM) who have received at least one prior therapy.
Off-label, however, Revlimid with dexamethasone is considered an appropriate induction regimen for potential transplant candidates since it does not possess bone marrow toxicity. It is listed as such, for example, by the NCCN.
It can also be used as maintenance, which has been studied in the post-transplant setting. Italian researchers presented the results of a study where Revlimid was administered as consolidation/maintenance therapy after a reduced-intensity autologous stem cell transplants in elderly patients with newly diagnosed myeloma. This study included over 100 patients aged 65-75 years with newly diagnosed myeloma. All received induction therapy with Velcade, dexamethasone, and doxorubicin followed by tandem autologous stem cell transplants with 100 mg/m2 of melphalan. Peripheral blood stem cells were harvested after Cytoxan and Neupogen® (figrastim). Revlimid was given after recovery from tandem autologous transplants. Starting dose was 10 mg/day, escalated to 15 mg/day after 3 months. Drug was held for ≥ Gr 3 toxicity, restarted at resolution to ≤ Gr 2 and was de- escalated by 5 mg or maintained at 5, 10 or 15 mg/day as tolerated. After consolidation/maintenance Revlimid, 88% of patients achieved at least a very good partial remission, and 53% a complete remission. One-year survival was 92%.
Results of the fifth interim analysis of this CALGB ECOG BMT-CTN 100104 trial showing data out to a median of 18 months were presented in Paris, France, at the 13th International Myeloma Workshop by principal investigator Philip McCarthy Jr, MD, director of the Blood & Marrow Transplant Program at Roswell Park Cancer Institute in Buffalo, New York in 2011. In this latest analysis, there continued to be a significantly longer time to progression in the patients who received lenalidomide therapy when compared with placebo. As of April 17, 2011, 69 of the original 231 lenalidomide patients experienced an event — disease progression or death — compared with 116 of the original 229 patients randomized to placebo (P < .0001), for a 56% reduction in the risk for disease progression in the lenalidomide arm (hazard ratio, 0.44; 95% confidence interval, 0.32 – 0.60).With regard to overall survival, patients receiving continuous lenalidomide therapy demonstrated an overall survival rate of 90% at more than 2 years after transplantation, compared with 83% for patients receiving placebo (P = .018).
However, this trial raised concerns because there appears to be a higher incidence of cancers in the Revlimid group. I In fact, all trials of Revlimid showed more cancers in patients on Revlimid; strangely, different types of cancers in different studies. The newest 2013 edition of the NCCN guideline lists Revlimid maintenance therapy as a “Category One″ recommendation, meaning the NCCN believes the recommendation is supported by “high-level evidence.
P. L. McCarthy, K. Owzar, K. C. Anderson, C. C. Hofmeister, H. Hassoun, D. D. Hurd, E. A. Stadtmauer, S. Giralt, V. Hars, C. A. Linker, for CALGB, ECOG and BMT-CTN; Roswell Park Cancer Institute, Buffalo, NY; Duke University Medical Center, Durham, NC; Dana-Farber Cancer Institute, Boston, MA; The Ohio State University, Columbus, OH; Memorial Sloan-Kettering Cancer Center, New York, NY; Wake Forest University, Winston Salem, NC; University of Pennsylvania Cancer Center, Philadelphia, PA; University of Texas M. D. Anderson Cancer Center, Houston, TX; University of California, San Francisco, San Francisco, CA Phase III intergroup study of lenalidomide versus placebo maintenance therapy following single autologous stem cell transplant (ASCT) for multiple myeloma (MM): CALGB 100104. J Clin Oncol 28:15s, 2010 (suppl; abstr 8017)
Matthew Strobeck From the analyst’s couch: Multiple myeloma therapies Nature Reviews Drug Discovery 6, 181-182 (March 2007)
Weber D, Chen C, Niesvizky R, et al. Lenalidomide Plus High-Dose Dexamethasone Provides Improved Overall Survival Compared to High-Dose Dexamethasone Alone for Relapsed or Refractory Multiple Myeloma (MM): Results of a North American Phase III Study (MM-009). Proceedings from the 42nd annual meeting of the American Society of Clinical Oncology. Atlanta, Ga. June 2006. Abstract # 7521.