Clinician-to-Clinician Update Clinician-to-Clinician Update

New Therapies for Hematologic Malignancies Show Promise

October 2015

Over the past 40 years, major therapeutic advances have dramatically improved survival rates for patients with hematologic malignancies, yielding overall 5-year survival rates of 83% for Hodgkin lymphoma, 68% for non-Hodgkin lymphoma, 54% for leukemia, and 43% for myeloma across all age groups in the United States.1 Experts with University of Minnesota Cancer Care continue their work toward furthering an improved survival rate and quality of life for these patients. Two recent trials show promise in this treatment area. One employs a novel immunotoxin for refractory B-cell malignancies, and another tests the use of an expanded pool of donors for patients receiving allogeneic blood or marrow transplantations as a therapy for lymphoma.

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— Figure 1. Structure of DT2219. The active domain of diphtheria toxin is fused to monoclonal antibodies that target CD22 and CD19, which are present on the cell membranes of malignant B cells.

Immunotoxin Therapy for Refractory B-cell Malignancies

Researchers at Masonic Cancer Center, University of Minnesota have recently completed a phase 1 study of a novel immunotoxin called DT2219. This immunotoxin fuses the active domain of diphtheria toxin with monoclonal antibodies targeting human CD19 and CD22 proteins on the surface of malignant B-cells.2 (See Figure 1.) In the study, 1 cycle of DT2219 was administered to 25 patients with relapsed/refractory B-cell lymphoma or leukemia.3 Treatment was well tolerated. Although the trial was only designed to test the safety of the immunotoxin, the study team was excited to see that some achieved major responses, one of which was a complete response. (See case study.) Based on these results, a phase 2 study exploring the efficacy and safety of multiple cycles of DT2219 is now enrolling.

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— Veronika Bachanova led a phase I clinical study of a promising immunotoxin, DT2219, developed by University of Minnesota colleague Daniel Vallera. (Photo by Scott Streble)

Expanding the Pool of Stem Cell Donors

In allogeneic blood or marrow transplantation (alloBMT) as a treatment for lymphoma, donors and recipients are precisely matched to ensure that they both share exactly the same proteins at 8 critical locations in the human leukocyte antigen (HLA) complex. Mismatches between patient and donor increase the risk of graft-versus-host disease, with a greater number of mismatches leading to a greater level of risk. Unfortunately, only about 50% of searches identify a suitable, matched donor for patients of European ancestry, and match rates are far lower for patients of other ethnic backgrounds.4

The team recently investigated alloBMT success rates in cases where the donor and patient had an HLA match at only 7 out of 8 locations (“7/8 match”).5 They found that the 3-year overall survival rate of patients who received a partially matched transplantation using umbilical cord blood or adult blood or marrow was comparable to that of patients who received a perfect matched donor graft. Further studies are ongoing to confirm and extend this exciting new treatment option for patients with lymphoma who lack a closely matched donor.

References

  1. United States Centers for Disease Control and Prevention. Cancer Survival Data. Available at https://nccd.cdc.gov/uscs/Survival/Relative_Survival_Tables.pdf. Accessed September 2, 2015.
  2. Vallera DA, Todhunter DA, Kuroki DW, et al. A bispecific recombinant immunotoxin, DT2219, targeting human CD19 and CD22 receptors in a mouse xenograft model of B-cell leukemia/lymphoma. Clin Cancer Res. 2005;11:3879-3888.
  3. Bachanova V, Frankel AE, et al. Phase I study of a bispecific ligand-directed toxin targeting CD22 and CD19 (DT2219) for refractory B-cell malignancies. Clin Cancer Res. 2015;21:1267-1272.
  4. Gragert L, Eapen M, Williams E, Freeman J, et al. HLA match likelihoods for hematopoietic stem-cell grafts in the U.S. registry. N Engl J Med. 2014;371(4):339-348.
  5. Bachanova V, Burns LJ, Wang T, et al. Alternative donors extend transplantation for patients with lymphoma who lack an HLA matched donor. Bone Marrow Transplant. 2015;50:197-203.

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Physician Outreach Program

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To schedule a physician meeting or to visit our facility, contact Melinda Arvold, Oncology Outreach Manager. Phone: 612-867-3411; email: marvold1@fairview.org.

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