Next Generation Treatments for Blood Cancers: Improved Outcomes in the Forecast

New therapies for hematologic malignancies have created a greater number of viable options for providers and patients, particularly for patients who have relapsed. Today’s armament includes chimeric antigen receptor (CAR) T-cells, bispecific antibodies and immunotherapeutic approaches, antibody conjugates, chemotherapy-free inductions and multi-drug combinations. The excitement surrounding these advances is palpable, as we are seeing improved outcomes in these very difficult-to-treat diseases. Yet the complexities of these therapies also bring their own complications.

In order to build upon our headway in the treatment of leukemia, lymphoma, multiple myeloma and stem cell transplantation, we must leave our research silos to share information and brainstorm with each other. That’s exactly what some of the nation’s top physician-scientists in the field did at Miami Cancer Institute’s Third Annual Summit of the Americas on Immunotherapies for Hematologic Malignancies, held April 8-9, 2022.

Among the topics were the role of the intestinal microbiome in hematopoietic stem cell transplantation and the influence of the gut’s microbial composition on graft versus host disease; the first in-human clinical trials using CRISPR/Cas9 technology to silence the expression of CD33 on stem cells and infuse the CD33-negative stem cells; and the shift from triplet combination therapies to four-drug regimens in multiple myeloma. The group also discussed BCMA-directed therapies for multiple myeloma, treatment approaches in diffuse large B-cell lymphoma and improving outcomes in T-ALL.

For example, Marcel van den Brink, M.D., Ph.D., of Memorial Sloan Kettering, referred to diet as a drug capable of preventing potentially lethal graft versus host disease. His work has explored the use of antibiotics to destroy specific gut flora and the introduction of fecal transplants to boost beneficial bacteria. A study published in the NEJM detailed the results of 8,767 fecal samples from patients undergoing allogeneic hematopoietic-cell transplantation at four centers. Patients with the highest diversity of intestinal microbiota had the lowest risk of death.¹

Hagop Kantarjian, M.D., from MD Anderson Cancer Center, shared the success of his research in chemotherapy-free induction and reduced toxicity regimens², particularly for older patients with acute lymphoblastic leukemia, a group whose complex disease has resulted in lower survival rates. The work holds considerable promise and brought about further talk of the possibility that the majority of these patients will no longer require allogeneic transplants.

Siddhartha Mukherjee, M.D., of Columbia University’s Herbert Irving Comprehensive Cancer Center, spoke on novel approaches of CAR T-cell therapies for acute myeloid leukemia, specifically the first-in-human clinical trial, “Allogeneic Engineered Hematopoietic Stem Cell Transplant (HCT) Lacking the CD33 Protein, and Post-HCT Treatment With Mylotarg, for Patients With CD33+ and AML.”³ Miami Cancer Institute is currently enrolling patients in the multi-site trial.

In addition, Dr. Mukherjee joined Richard Stone, M.D., and Robert Soiffer, M.D., both of Dana-Farber Cancer Institute, for a fast-paced roundtable discussion on the newest treatments for AML.

As these new techniques evolve and we adjust conditioning regimens, induction timing and dosing levels, as well as introducing different drug combinations, we are very hopeful that we will continue to see improved outcomes. Through intimate meetings such as the Summit, which provide participants with the opportunity to ask questions and talk one-on-one and in small group settings with each other, we will change the cancer care environment. Watch for more information soon on the Fourth Annual Miami Cancer Institute Summit of the Americas on Immunotherapies for Hematologic Malignancies.

_References

_{1. Microbiota as Predictor of Mortality in Allogeneic Hematopoietic-Cell Transplantation. Accessed April 12, 2022. https://www.nejm.org/doi/full/10.1056/NEJMoa1900623}

_{2. Optimizing the use of the hyperCVAD regimen: Clinical vignettes and practical management. https://acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.32606}

_{3. Allogeneic Engineered Hematopoietic Stem Cell Transplant (HCT) Lacking the CD33 Protein, and Post-HCT Treatment With Mylotarg, for Patients With CD33+ and AML. https://clinicaltrials.gov/ct2/show/NCT04849910}