Marcela F Pasetti

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Lenalidomide-induced immunomodulation in multiple myeloma: impact on vaccines and antitumor responses.

Kimberly Noonan; Lakshmi Rudraraju; Anna Ferguson; Amy Emerling; Marcela F Pasetti; Carol A Huff; Ivan Borrello (Profiled Author: Marcela F Pasetti)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins Medicine, Baltimore, Maryland 21231, USA.
Clinical cancer research : an official journal of the American Association for Cancer Research 2012;18(5):1426-34.

PURPOSE: To show that the immunomodulatory drug lenalidomide can be used in patients with relapsed multiple myeloma to augment vaccine responses. EXPERIMENTAL DESIGN: Early phase clinical trial of patients with multiple myeloma who received at least one prior therapy. Patients were treated with single-agent lenalidomide and randomized to receive two vaccinations with pneumococcal 7-valent conjugate vaccine (PCV) on different schedules. Cohort A received the first PCV vaccination prior to the initiation of lenalidomide and the second vaccination while on lenalidomide. Cohort B received both vaccinations while on lenalidomide. RESULTS: PCV-specific humoral and cellular responses were greater in cohort B than A and were more pronounced in the bone marrow than the blood, suggesting that maximal vaccine efficacy was achieved when both vaccines were administered concomitantly with lenalidomide. Patients with a clinical myeloma response showed evidence of a tumor-specific immune response with increases in myeloma-specific IFN-γ(+) T cells and reductions in Th-17 cells. CONCLUSIONS: This is the first clinical evidence showing that lenalidomide augments vaccine responses and endogenous antitumor immunity in patients and as such may serve as an adjuvant for cancer and possibly infectious vaccines.

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