Hematology

Abstract

With modern intensive combination polychemotherapy, the complete response (CR) rate in adults with acute lymphoblastic leukemia (ALL) is 80-90%, and the cure rate 40-50%. Hence there is a need to develop effective salvage therapies and combine novel agents with standard effective chemotherapy. ALL leukemic cells express several surface antigens amenable to target therapies, including CD20, CD22, and CD19. Monoclonal antibodies target these leukemic surface antigens selectively, and minimize off-target toxicity. When added to frontline chemotherapy, rituximab, an antibody directed against CD20, increases cure rates of adults with Burkitt leukemia from 40% to 80%, and those with pre-B ALL from 35% to 50%. Inotuzumab ozogamicin, a CD22 monoclonal antibody bound to calicheamicin, has resulted in marrow CR rates of 55% and a median survival of 6-7 months when given to patients with refractory-relapsed ALL. Blinatumomab, a biallelic T-cell engaging CD3-CD19 monoclonal antibody, also resulted in overall response rates of 40-50% and a median survival of 6.5 months in a similar refractory-relapsed population. Other promising monoclonal antibodies targeting CD20 (ofatumumab, obinutuzumab), or CD19 or CD20 and bound to different cytotoxins or immunotoxins are under development. Combined modalities of chemotherapy and the novel monoclonal antibodies are under investigation.

From Youtube, by: ImedexCME Filmed on location in Barcelona, Spain during the 11th European Congress on Hematologic Malignancies, this webcast is part of a series that provides cutting-edge updates and expert perspectives on the diagnosis and management of hematologic malignancies, including multiple myeloma, chronic lymphocytic leukemia, and Hodgkin's and non-Hodgkin's lymphomas. By combining stimulating didactic sessions, interactive panel discussions, and lively debates by internationally renowned specialists, presentations from this Congress supply healthcare professionals with the information they need to optimize care and outcomes for their patients with hematologic malignancies.

Abstract

With optimal target antigen selection antibody-based therapeutics can be very effective agents for hematologic malignancies, but none have yet been approved for myeloma. Rituximab and brentuximab vedotin are examples of success for the naked antibody and antibody–drug conjugate classes, respectively. Plasma cell myeloma is an attractive disease for antibody-based targeting due to target cell accessibility and the complementary mechanism of action with approved therapies. Initial antibodies tested in myeloma were disappointing. However, recent results from targeting well-characterized antigens have been more encouraging. In particular, the CD38 and CD138 targeted therapies are showing single-agent activity in early phase clinical trials. Here we will review the development pipeline for naked antibodies and antibody–drug conjugates for myeloma. There is clear clinical need for new treatments, as myeloma inevitably becomes refractory to standard agents. The full impact is yet to be established, but we are optimistic that the first FDA-approved antibody therapeutic(s) for this disease will emerge in the near future.