Filling the Gap: The Immune Therapeutic Armamentarium for Relapsed/Refractory Hodgkin Lymphoma

Abstract

Despite years of clinical progress which made Hodgkin lymphoma (HL) one of the most curable malignancies with conventional chemotherapy, refractoriness and recurrence may still affect up to 20-30% of patients. The revolution brought by the advent of immunotherapy in all kinds of neoplastic disorders is more than evident in this disease because anti-CD30 antibodies and checkpoint inhibitors have been able to rescue patients previously remaining without therapeutic options. Autologous hematopoietic cell transplantation still represents a significant step in the treatment algorithm for chemosensitive HL; however, the possibility to induce complete responses after allogeneic transplant procedures in patients receiving reduced-intensity conditioning regimens informs on its sensitivity to immunological control. Furthermore, the investigational application of adoptive T cell transfer therapies paves the way for future indications in this setting. Here, we seek to provide a fresh and up-to-date overview of the new immunotherapeutic agents dominating the scene of relapsed/refractory HL. In this optic, we will also review all the potential molecular mechanisms of tumor resistance, theoretically responsible for treatment failures, and we will discuss the place of allogeneic stem cell transplantation in the era of novel therapies.

Keywords: CAR-T cells; Hodgkin Lymphoma; immune escape; immunotherapy; mechanisms of resistance.

Figure 1

(A) Incidence and mortality of HL (cumulative rate per 100,000) grouped by sex across the time. Lines are smoothed by the locally weighted linear regression (LOESS) algorithm. Rates are shown on a semi-logarithmic scale. (B) Incidence and mortality of HL (rate per 100,000) by sex across ages. Rates are shown on a semi-logarithmic scale. (C) Relationship between incidence and mortality across countries (indicated as an age-standardized rate -ASR). (D) Map showing the estimated crude incidence rates in 2020, for HL in both sexes and across all ages. Data used to generate this figure were extracted from the Global Cancer Observatory project (International Agency for Research on Cancer).

Figure 2

Timeline history of FDA approvals in Hodgkin lymphoma.