Lack of Response to Vaccination in MGUS and Stable Myeloma.
Authors: Prabhala Rao H , Efebera Yvonne A , Lee Saem , Han Andrew J , Pelluru Dheeraj , Nanjappa Puru , Amin Samir , Pai Christine , Ghobrial Irene , Schlossman Robert L , Laubach Jacob , Fulciniti Mariateresa , Richardson Paul , Anderson Kenneth C. , Munshi Nikhil C. 
Published: October 2019

Abstract 1852

Poster Board I-878

Multiple myeloma patients suffer from infection related complications. Abnormalities in both cellular and humoral immune responses have been considered responsible. Patients have been routinely immunized with vaccinations to prevent infection related problems, however, efficacy of such vaccination in early or stable myeloma remains unclear. Previously, we have shown immunomodulatory and T cell co-stimulatory effects of lenalidomide, which can up-regulate cellular immune responses in myeloma. Based on these results we initiated a study to evaluate the efficacy of lenalidomide compared to placebo on the effect of Hepatitis B (HepB) vaccination in patients with monoclonal gamopathy of undetermined significance (MGUS), smoldering myeloma or stable multiple myeloma (MM) not requiring any therapy. Patients were randomized to lenalidomide or placebo for 14 days with HepB vaccination on day 8. They were given option for 2nd and 3rd HepB vaccinations at 1 month and 6 month. Primary objective was to evaluate antibody response to Hepatitis Surface antigen (HepBSAg) at 1 month after vaccination. We also measured HepBSAg-specific cellular immune responses using HepBSAg protein and HLA-A2 peptide. At the time of data analysis, the study remains blinded. Thirty two patients have completed their initial vaccination (25 MGUS and 7 MM), while 22 patients (16 MGUS, 6 MM) have completed 3 vaccinations with 6 months follow up. None of the 32 patients, with MGUS or MM, had antibody response to vaccination at 1 month; while after 3 vaccination only 30% patients (7 of 24) demonstrated antibody response to HepBSAg (titer values 128.4±36.4). This is significantly below responses reported in literature in healthy individuals (90%). Responses in patients with MGUS (4 of 16) were not significantly different than in patients with MM (3 of 6). No base line patient characteristics predicts responders vs. non-responders. We have further analyzed HepBSAg-specific T cell immune response by detecting the presence of pentamer-positive CD8 cells with HepB surface antigen-peptide in HLA-A2+ samples. Five of seven responders were HLA-A2 positive, and none of them showed T cell response to HbSAg following vaccination as detected by change in pentamer positive cells. Three patients showed T cell-proliferative responses to HepBsAg; one of which had long term response. None of the non-responders tested demonstrated proliferative response to HepBSAg. The randomization remains blinded at the moment and hence effect of lenalidomide on immune response is not available at the present time. These results have very high clinical significance. It suggests that even in MGUS there is significant and profound functional immune suppression. Strategies to prevent infection and improve immune responses needs to be developed for both preventative purposes as well as for anti-MM vaccinations.

Disclosures:

Laubach: Novartis: . Richardson:Keryx Biopharmaceuticals: Honoraria. Anderson:Millenium: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding.