Reflections on Immunotherapies for Hematologic Malignancies From MCI’s Fifth Annual Summit

Guenther Koehne, MD, PhD, deputy director and chief of Blood & Marrow Transplant and Hematologic Oncology at Miami Cancer Institute of Baptist Health South Florida, highlights the importance of and the key takeaways from the Fifth Annual Miami Cancer Institute Global Summit on Immunotherapies for Hematologic Malignancies.

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0:09 | This is the Miami Cancer Institute Global Summit on Immunotherapies for Hematologic Malignancies. This is really important for many reasons. Number 1, we get the lead physicians from all over the world to come to present and update us on the rapid development of the treatment of hematologic malignancies. In addition, it it a very intimate exchange of information between the speakers, faculty, attendees, and also the sponsors and pharmaceutical supporters that increasingly come to this meeting. I am very proud to have everybody in the same room.

0:47 | Everybody in the field of hematologic malignancies or such immunotherapies, which includes the [chimeric antigen receptor (CAR)] T-cell therapies, bispecific antibody therapies, antibody-drug conjugates, stem cell transplantations, is invited to come. It does not exclude anybody that is interested, mostly physicians, nurses and [advanced practice providers] in the field, pharmaceutical companies, and pharmacy pharmacists are all welcome to attend.

1:15 | I attend a lot of international meetings, big meetings, like the American Society of Hematology meeting or transplant meetings. There you run from 1 room to the other and catch up with some information that you may want to be interested in. But here you really have the opportunity to talk to each other during the breaks and during the sessions. We have a good, qualified speaker podium and questions being asked to address that would likely not be addressed at these bigger meetings. It is an entry for everybody that is interested in hematologic malignancies. This field is developing so rapidly, it is getting more and more complex. I think everybody is interested in cancer treatment, and that does not exclude the solid tumor physicians because the solid tumor field is still behind with respect to immunotherapy specifically targeting the disease as we used to do it now for the malignancies.

2:15 | Allogeneic stem cell transplantation and the outcomes thereof has improved over the last year significantly, but we can still do better. One of the complications that has always been under discussion is the development of acute and or chronic graft-versus-host disease. My goal has been to eliminate or to prevent the development rather than to treat chronic graft-versus-host disease with the elimination of the T cells that come from the donor and that is by performing CD34 selected allogeneic stem cell transplants, we completely eliminate the development of graft-versus-host disease, chronic graft-versus-host disease. In addition, we do not have to administer immunosuppressive therapy which is required after non T-cell depleted transplants and they have [adverse] effects of their own. That is step number 1. Now, this transplant form is associated likely with a little bit higher transplant-related mortality, which is induced mostly by viral reactivations. But those studies have been performed and published before we administered viral prophylaxis, particularly viral prophylaxis with letermovir for CMV reactivation has changed the outcome significantly. We do not see CMV reactivation anymore at these high percentages, and we do not see CMV disease anymore, so that transplant-related mortality is significantly reduced.

3:43 | Now during my presentation, I also addressed a new approach to prevent or to treat relapse post transplantation, which is unavoidable for some high-risk acute myeloid leukemia, such as TP53-mutated AML or FLT3-mutated AML. Therefore, we need to do more to prevent or treat early recurrence of this disease. Now, the problem here is that the targeting of the leukemia cells is also combined with the targeting of the healthy hematopoietic stem cell because the microscope can be targeted expressed on both cell types. With that, now we have a new innovative approach with CRISPR technology to downregulate the expression of CD33 on the healthy hematopoietic stem cells and transplant patients with C34-selected, CD33-negative hematopoietic stem cells, and therefore, the only cell left after this transplant is the leukemia cell that still expresses CD33. We can specifically target these leukemia cells with gemtuzumab [Mylotarg] or with one of the CAR T cells specifically targeting CD33. That is the new development, very innovative, very promising.

4:56 | There are a lot of new developments, particularly for the treatment of non Hodgkin lymphoma to treat CAR T cells with bispecific or dual specific CAR T cells targeting 2 markers at the same time, such as CD19 and CD20, preventing recurrence at an early stage, hopefully. Particularly, it was just addressed that the CAR T-cell therapies for acute myeloid leukemia is now possible with the gene editing of the transplant product before the transplant. Then, we have the opportunity to administer post transplantation targeted therapies for patients with high-risk acute myeloid leukemia.

5:33 | It is March in Miami and that is a good ground to come from Boston or New York City or from the East Coast. Now, I think this symposium has had a great development and has a good reputation. I think everybody, including the speakers, the pharmaceutical sponsors, are eager to come back and communicate their new products and the new information and the results of new clinical trials that develop so rapidly every year.

6:04 | [I am] unlimitedly proud to have everybody here in the same room. I think everybody that sees me on stage can appreciate the level of proudness that I have. Now, I am extremely proud to have everybody here and I am absolutely grateful and thankful that everybody came and came back to join this wonderful meeting.