Lenalidomide Immunomodulation with an Allogeneic Myeloma GVAX in a Near Complete Remission Induces Durable Clinical Remissions

Background: Increasing evidence suggests that the depth of response in myeloma (MM) correlates with delayed time to progression¹.We have previously shown that lenalidomide (Len) can augment vaccine efficacy to the pneumococcal conjugate vaccine (PCV), Prevnar².We extend those observations to examine whether vaccinating patients on Len in a near complete remission (nCR) (negative M-spike, IFE positive) could further deepen the clinical response and generate measurable myeloma specific immunity in a small Phase II study.

Design:Patients needed to be on a Len-containing regimen and needed to be in one of the following categories for enrollment: 1) in a stable nCR for at least 4 months; 2) converting from IFE negative to IFE positive; or 3) showed signs of early relapse from a nCR to an M-spike <0.3g/dL. Patients would be continued on single agent Len and receive 4 vaccinations consisting of two allogeneic MM lines, H929, U266 admixed with K562 transduced to express GM-CSF as well as PCV. Patients received 3 monthly vaccines and a boost at 6 months.

Results: To date 32 patients have been screened: 12 had relapsed and 5 entered into an IFE negative CR during the 4 month observation period; 11 have been enrolled. Median follow-up for the study is 13.9 months. Of the vaccinated patients, category 1: 4 patients: 3 are in a true CR (IFE-),1 lost the original clone and is still in a nCR. Category 2: 2 patients both achieved a true CR. Category 3: 5 patients: 2 stable disease, 3 progressive disease. The overall true CR rate is 54%.of the patients that achieved a CR with a median follow-up of 17.1 months. Laboratory analysis showed that the patients achieving a CR had more central memory CD8 T cells at baseline in the BM and blood, a greater activation phenotype in CD8 cells in the BM and greater tumor specific IFNg production. Interestingly, LAG-3, TIM-3 and PD-1 on CD8 T cells were more expressed in the BM of CR patients.

Conclusions: Vaccination in combination with Len appears to durably deepen the clinical response in patients in a nCR whereas patients with early relapse appear less likely to respond. The deepening the clinical response correlates with the development of myeloma-specific immunity. Vaccination of MM patients in nCR in combination with Len shows promising early clinical activity that warrants further investigation as an approach to maintaining durable clinical remissions.

1.Chanan-Khan, A.A., and S. Giralt. 2010. Importance of achieving a complete response in multiplemyeloma, and the impact of novel agents. J Clin Oncol 28:2612-2624.

2. Noonan, K., L. Rudraraju, A. Ferguson, A. Emerling, M.F. Pasetti, C.A. Huff, and I. Borrello. 2012. Lenalidomide-induced immunomodulation in multiple myeloma: impact on vaccines and antitumor responses. Clin Cancer Res 18:1426-1434.