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Consult

Clinician-to-Clinician Update
To schedule a consultation, referral or appointment:
For referral to bone marrow or cell therapy programs:

Masonic Cancer Clinic
Clinics and Surgery Center
909 Fulton St., SE, Suite 202
Minneapolis, MN 55455

For information on blood and marrow transplant services, visit mhealth.org/bmt

CAR T-Cell and New Immunotherapies Hold Promise in Treating a Range of Cancers

Recent, rapid advances in immunotherapy have brought new treatment options to cancer patients, potentially positioning it among the established therapeutic approaches to cancer. The chimeric antigenic receptor (CAR) T-cell therapies Kymriah and Yescarta, approved by the Food and Drug Administration in 20171, have generated extensive interest. Other immunotherapies, including natural killer (NK) cell therapies, have also emerged and, like CAR T-cell therapy, may hold promise in the treatment of a range of cancers, including solid tumor malignancies.

Veronika Bachanova
University of Minnesota Health hematologist-oncologist Veronika Bachanova, MD, conducts research into CAR T-cell and NK cell therapies.
Kymriah (tisagenlecleucel), approved in 2017 for the treatment of refractory or relapsed B-cell precursor acute lymphocytic leukemia (ALL) in patients 25 years of age or younger, and Yescarta (axicabtagene ciloleucel), approved for treatment of diffuse large B-cell lymphoma (DLBCL) in adults, have both shown striking success. Of patients with B-cell precursor ALL treated in the Kymriah clinical trial, 63% achieved remission.2 Among patients with relapsed DLBCL in the Yescarta study, 72% of patients responded to the treatment, with 51% achieving complete remission.1 More than 40% were still in remission 15.4 months post-treatment.3 In May 2018, Kymriah was also approved for treatment of adults with relapsed or refractory large B-cell lymphoma after 2 or more lines of systemic therapy. The CD19-directed CAR T-cell therapies also hold promise as treatment options for other subtypes of aggressive B-cell lymphomas. 

Made from the patient’s T-lymphocytes, CAR T-cell therapy entails genetically engineering the patient’s collected T-cells so that they produce proteins that bind tumor-specific antigens on cancer cells. The engineered T-cells are expanded and then infused into the patient. CAR T-cell therapy is the first genetic therapy approved for cancer treatment, and while expensive, it has demonstrated remarkable efficacy in patients without other therapeutic options. Because CAR T-cell therapy has been associated with cytokine release syndrome (CRS) and neurologic complications,4 careful post-therapeutic monitoring is required. Treatment of CRS may include tocilizumab or steroids. Refinements in CAR T-cell design may improve toxicity-to-efficacy index.4 

Researchers, including physicians at the University of Minnesota, are exploring additional immunotherapies against leukemia, lymphomas, myeloma, and solid cancers. Solid cancers and tumors pose challenges for immunotherapy approaches, since they are dense and offer limited surfaces for drug infiltration and their heterogeneous and immunosuppressive microenvironments also impose limitations.5 

NK cell therapies may present an accessible and effective treatment option for both hematologic and solid tumors.5,6 Cytotoxic lymphocytes that do not require antigen priming, NK cells attack cancer cells without major histocompatibility complex presentation. They are easily isolated and do not require donor matching. In a recent phase II trial, NK-cell infusion and interleukin-2 was tolerated by patients with poor-prognosis, refractory non-Hodgkin lymphoma without incidence of graft-versus host disease, CRS, or neurotoxicity.7 It has also shown promise with refractory or relapsed acute myelogenous leukemia. 

Novel methods for generating target-specific NK cells may advance development of future NK cell therapies.8 Treatments are being developed to overcome innate obstacles and improve specificity, and multiple clinical trials are underway. At the Masonic Cancer Center, University of Minnesota, currently enrolling phase I trials will explore NK cell therapies as potential treatments for acute myelogenous leukemia, myeloma, and solid cancers, including ovarian, colorectal, and breast cancer. (See Specialty Updates for further information.)

References

  1. Bouchkouj N, Kasamon YL, de Claro RA, et al. FDA approval summary: axicabtagen diloleucel for relapsed or refractory large B-cell lymphoma. Clin Cancer Res. 2018 Nov 9; [Epub ahead of print] pii: clincanres.2743.2018. doi: 10.1158/1078-432.CCR-18-2743 
  2. O’Leary MC, Lu X, Huang Y, et al. FDA approval summary: tisagenlecleucel for treatment of patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia. Clin Cancer Res. 2018 Oct 11; [Epub ahead of print] doi: 10.1158/1078-0432.CCR-18-2035 
  3. Neelapu SS, Locke FL, Bartlett NL, et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017; 377: 2531-2544. 
  4. Fang N, Zhong N, Gu T, Wang Y, Guo X, Ji S. A quantitative method for measuring the transfection efficiency of CD 19-directed chimeric antigen receptor in target cells. Adv Clin Exp Med 2018 Dec 5 [Epub ahead of print] doi: 10.17219/acem/90772 
  5. Shapovalova M, Pyper SR, Moriarity BS, LeBeau AM. The molecular imaging of natural killer cells. Mol Imaging. 2018 Jan-Dec;17:1536012118794816. doi: 10.1177/1536012118794816 
  6. Johnson JK, Miller S. Current strategies exploiting NK-cell therapy to treat hematologic malignancies. Int J Immunogenet. 2018 Jul 16; [Epub ahead of print] doi: 10.1111/iji.12387 
  7. Bachanova V, Sarhan D, DeFor TE, et al. Haploidentical natural killer cells induce remissions in non-Hodgkin lymphoma patients with low levels of immune-suppressor cells. Cancer Immunol Immunother. 2018 Mar;67(3):483-494. doi: 10.1007/s00262-017-2100-1 
  8. Grzywacz B, Moench L, McKenna D Jr, et al. Natural killer cell homing and persistence in the bone marrow after adoptive immunotherapy correlates with better leukemia control. J Immunother. 2018 Nov 27 [Epub ahead of print]. DOI: 10.1097/CJI.0000000000000250

When to Refer

The University of Minnesota Health Cancer Care hematology, oncology, and transplantation teams offer comprehensive diagnosis and treatment of patients with malignancies, including lymphoma, leukemias, multiple myeloma, and other cancers. Treatment regimens are individually tailored and include chemotherapy, targeted therapy with drugs or protease inhibitors, high-dose chemotherapy with stem cell transplantation, biologic or immune therapies, radiation, and surgery. We are 1 of only a few cancer centers currently certified to offer CD19- directed CAR T-cell therapies, new therapeutic options for patients whose therapies have failed against pediatric acute lymphocytic leukemia or diffuse large B-cell lymphoma.

Through our partnership with the Masonic Cancer Center, University of Minnesota, we participate in multiple clinical trials assessing new cutting-edge therapies for cancer and solid tumors.

Collaborative Care 

We work hard to keep referring providers informed of their patients’ care by providing detailed reports, from diagnosis to treatment and follow-up. Our goal is to provide prompt service and communication for the patients referred to us. We seek to expedite therapies to minimize trips to the Twin Cities. In many cases, care after discharge can also be provided locally. 

Physician Outreach Program

The Cancer Care Outreach Program is designed to provide education and facilitate knowledge sharing between our team and the medical community. To schedule a physician meeting or to visit our facility, contact Melinda Tuma, System Manager, Outreach Services. Phone: 612-273-9947; Email.

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