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-cell therapy, bispecific antibodies, immunotherapeutic approaches, antibody-drug conjugates, chemotherapy-free inductions, and multidrug combinations. The excitement surrounding these advances and improved outcomes in very difficult-to-treat diseases is palpable. Yet the complexities of these therapies also bring their own complications.

In order to build upon the headway made in the management of leukemia, lymphoma, multiple myeloma, and stem cell transplantation, clinicians must leave their research silos to share information and brainstorm with each other. That’s exactly what some of the nation’s top physicianscientists did at the 3rd Annual Miami Cancer Institute Summit of the Americas on Immunotherapies for Hematologic Malignancies, held April 8-9, 2022, in Florida.

For example, Siddhartha Mukherjee, MD, of Columbia University Herbert Irving Comprehensive Cancer Center in New York, New York, spoke on novel approaches of CAR T-cell therapies for acute myeloid leukemia (AML), 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 (NCT04849910). The Miami Cancer Institute is currently enrolling patients in the multisite trial.

Mukherjee joined Richard Stone, MD, and Robert J. Soiffer, MD, both of Dana-Farber Cancer Institute in Boston, Massachusetts, for a fast-paced roundtable discussion on the newest treatments for AML.

Among the topics reviewed were the role of the intestinal microbiome in hematopoietic stem cell transplantation and the influence of the gut’s microbial composition on graft-vs-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 4-drug regimens in multiple myeloma. The group also discussed B-cell maturation antigen–directed therapies for multiple myeloma, treatment approaches in diffuse large B-cell lymphoma, and improving outcomes in T-cell acute lymphoblastic leukemia (ALL).

In another presentation, Marcel R. M. van den Brink, MD, PhD, the Alan N. Houghton Chair and head of the Division of Hematologic Malignancies at Memorial Sloan Kettering Cancer Center in New York, New York, referred to diet having a role in preventing potentially lethal graft-vs-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 New England Journal of Medicine detailed the results of 8767 fecal samples from patients undergoing allogeneic hematopoietic cell transplantation at 4 centers. Patients with the highest diversity of intestinal microbiota had the lowest risk of death (HR, 0.71; 95% CI, 0.55-0.92).¹

In his presentation on treatment updates for ALL, Hagop M. Kantarjian, MD, a professor and Samsung Distinguished Leukemia Chair in Cancer Medicine at The University of Texas MD Anderson Cancer Center in Houston, shared the success of his research in chemotherapyfree induction and reduced toxicity regimens,² particularly for older patients with ALL, a group whose complex disease has resulted in lower survival rates. The work holds considerable promise, prompting talk of the possibility that the majority of these patients will no longer require allogeneic transplants.

There is great hope for continued improved outcomes as these new techniques and strategies evolve; conditioning regimens, induction timing and dosing levels are adjusted; and different drug combinations are introduced. Through intimate meetings such as the summit, which provide participants the opportunity to ask questions and talk one-on-one and in small group settings, the cancer care environment will continue to evolve.

Watch for more information on the Miami Cancer Institute’s 4th Annual Summit of the Americas on Immunotherapies for Hematologic Malignancies.

REFERENCES

1. Peled JU, Gomes ALC, Devlin SM, et al. Microbiota as predictor of mortality in allogeneic hematopoietic-cell transplantation. N Engl J Med. 2020;382(9):822-834. doi:10.1056/NEJMoa1900623

2. Rausch CR, Jabbour EJ, Kantarjian HM, Kadia TM. Optimizing the use of the hyperCVAD regimen: clinical vignettes and practical management. Cancer. 2020;126(6):1152-1160. doi:10.1002/cncr.32606