Most adverse events were grade 1/2; the most frequent of these were anemia and infusion-related reactions.2 Anemia was an expected, on-target toxicity and was manageable; few dose-limiting toxicities occurred.

If the findings are confirmed in subsequent clinical testing and are shown to benefit patients, the regimen could help to address a current treatment gap for many patients.3 The standard of care for patients with B-cell lymphomas is chemoimmunotherapy, but many patients have refractory disease or experience relapse, the authors noted.2 In addition, some patients cannot undergo chemotherapy.

The findings were striking because of the low reported toxicity rates seen in patients enrolled in the trial and how rapidly and durably responses were observed, wrote Alberto Mantovani, MD, the Humanitas Clinical and Research Center, Humanitas University, Milan, Italy, and Dan Longo, MD, of the William Harvey Research Institute, Queen Mary University of London, England, in a commentary that was published alongside the study findings.3


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The study builds on previous, preclinical research that suggests CD47 blockade might activate T-cell–mediated antitumor activity, in addition to contributing to phagocytosis of cancer cells.1,3-5

“Recent biologic insights regarding immune evasion by lymphomas have enabled the development of multiple promising immunotherapeutic strategies,” Dr Advani and colleagues wrote.2

That work is now undergoing clinical translation.1,3-5 In addition to the 5F9 plus rituximab NHL study, there are 4 other clinical trials under way to test 5F9 as an anticancer therapy: in combination with cetuximab for advanced colorectal cancers and other solid tumors, with or without azacitidine in acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS), and with avelumab in ovarian cancer and as a monotherapy for relapsed/refractory AML.5

CD47 blockade might also be enhanced by targeting other molecular checks on phagocytosis, other researchers have proposed.4

Preclinical work with tumor tissue in vitro and in xenograft models at Stanford University’s Lucile Packard Children’s Hospital and Institute of Stem Cell Biology & Regenerative Medicine suggests that 5F9 may be effective in stimulating immune cell attacks against several aggressive forms of pediatric brain tumors, including glioblastoma, primary and metastatic group 3 medulloblastomas, teratoid rhabdoid tumor, primitive neuroectodermal tumor, and diffuse intrinsic pontine glioma.6

Disclosure: The 5F9 plus rituximab NHL trial was sponsored by Forty Seven, Inc., and The Leukemia and Lymphoma Society. For a full list of disclosures, please refer to the original study.

References

  1. Russ A, Hua AB, Montfort WR, et al. Blocking “don’t eat me” signal of CD47-SIRPα in hematological malignancies, an in-depth review. Blood Rev. 2018;32(6):480-489.
  2. Advani R, Flinn I, Popplewell L, et al. CD47 blockade by Hu5F9-G4 and rituximab in non-Hodgkin lymphoma. New Engl J Med. 2018;379(18):1711-1721.
  3. Mantovani A, Longo DL. Macrophage checkpoint blockade in cancer—back to the future. N Engl J Med. 2018;379(18):1777-1779.
  4. Veillette A, Chen J. SIRPα-CD47 immune checkpoint blockade in anticancer therapy. Trends Immunol. 2018;39(3):173-184.
  5. National Cancer Institute (NCI). Clinical trials using anti-CD47 monoclonal antibody Hu5F9-G4. Accessed December 13, 2018.
  6. Gholamin S, Mitra SS, Feroze AH, et al. Disrupting the CD47-SIRPα anti-phagocytic axis by a humanized anti-CD47 antibody is an efficacious treatment for malignant pediatric brain tumors. Sci Transl Med. 2017;9(381):eaaf2968.