Hybridoma-Derived Idiotype Vaccine for Lymphoma: Approval Must Wait.

Maurizio Bendandi

doi:10.3390/ph3030667

Abstract

Hybridoma-derived idiotype vaccines have been used for the experimental treatment of human lymphoma over the last twenty years, providing evidence of biological efficacy, clinical efficacy and clinical benefit. However, the product that has come closer to regulatory approval is unlikely to clear that hurdle due to the insufficiently robust data obtained in a recently closed clinical trial. This review aims at discussing the reasons for hybridoma-derived idiotype vaccines, more difficult to produce but also more successful than recombinant idiotype vaccines so far, are unlikely to gain regulatory approval. In particular, it is necessary to examine the many peculiar features of this therapeutic approach in a broader context, with special attention to concepts like customized active immunotherapy and randomization. Most published trials based on hybridoma-derived idiotype vaccines are being analyzed, together with the yet non-peer reviewed data from the only randomized study conducted so far with this product, and with the main trials on recombinant idiotype vaccines for thorough comparison. All in all, the sole randomized trial ever conducted on hybridoma-derived idiotype vaccines failed to achieve its primary clinical end point because of an insufficient accrual and because the statistical significance achieved was not as stringent as required for regulatory approval.

Highlights

The estimated 66,000 new cases over this year make of non-Hodgkin’s lymphoma (NHL) the most common hematologic malignancy in the United States [1]
These two B-cell NHL subtypes are the sole in which hybridoma-derived idiotype vaccines have been tested so far, with the former having been the subject of the vast majority of such clinical trials [3]
At least in principle, any B-cell NHL subtype whose cells express on their surface either a complete clonal immunoglobulin or at least some of its idiotopes [4] could be treated with an idiotype vaccine with the aim of preventing disease relapse once a clinical response has been achieved through standard of care therapy [5]

Summary

Introduction

The estimated 66,000 new cases over this year make of non-Hodgkin’s lymphoma (NHL) the most common hematologic malignancy in the United States [1]. The anti-CD20 monoclonal antibody rituximab has revolutionized the way oncologists treat FL, MCL and virtually any other CD20-positive B-cell NHL, to such an extent that the combination of rituximab and different chemotherapy regimens is the standard of care for most if not all B-cell lymphoma [6]. With these combinations both higher response rates and longer response duration are systematically achieved compared to those obtained by chemotherapy alone [6]. Vaccines are those with the longest track record (Table 1), none of them has yet either made it to the market or gained regulatory approval [3]

Introduction to the Compound

Findings

Conclusions