Stem Cell Transplantation Delivers in Treating Blood Cancer

Guenther Koehne, MD, PhD

Over the past few decades, the landscape of blood cancer treatment has undergone a remarkable transformation. We have a deeper understanding of the molecular and genetic basis of blood cancers, and there have been rapid developments in the realm of immunotherapy and targeted therapies.

Among the most revolutionary therapies for hematologic malignancies is stem cell transplantation, which had its beginnings in the 1950s. Allogeneic transplant is, today, a curative therapy for a variety of blood cancers, including many cases of acute monocytic leukemia (AML), acute lymphoblastic leukemia (ALL) and myelodysplastic syndromes.

Focus on Key Pillars

It’s crucial that we make the next leap in the transformation of care for our patients, and to do so we must continue to remain focused on key aspects that greatly affect outcomes, including:

• Conditioning regimens – to reduce pre-transplantation toxicities and complications

• Graft-versus-host disease (GVHD) risk – to lessen the chance of a life-threatening complication through the use of graft manipulation or posttransplantation cytotoxin administration

• Relapse – to enhance relapse management by integrating maintenance treatments, early management at the first signs of minimal residual disease or of relapse, bolstering the graft’s ability to recognize and attack residual malignant cells and potential infusions of CAR T cells derived from the original or from a third-party donor as an approach to prevent or treat relapse post stem cell transplant

• Infectious complications – to reduce the risk of viral infections and reactivations, using antimicrobial prophylaxis, by continuing close monitoring and administration of anti-viral specific immune cells

A plethora of research in these areas is already leading ― and will continue to lead ― to changes that impact outcomes. For example, O’Reilly et al,¹ determined that consistent engraftment and lower incidences of acute and chronic GVHD occurred when allogeneic hematopoietic cell transplantation (HCT) depleted of T-cells were administered after myeloablative chemotherapy in patients.¹ The work of Kosuri et al, in identifying a variety of cardiovascular, hematologic, and renal toxicities that contribute to morbidity and mortality in the first year of treatment in adults who undergo myeloablative allogeneic HCT with ex vivo CD34+ selection, helped establish a benchmark for toxicity reduction.²

Relapse continues to be of high concern, as well, and at the European Hematology Association 2023 meeting in June, we presented results of study VBP101 (NCT04849910), a first-in-human clinical trial utilizing CD34+ selected allografts with gene-edited CD33-negative hematopoietic stem cells from HLA matched related or unrelated donors for patients with AML. The VBP101 trial is a phase 1/2a multicenter study looking at the combination of trem-cel and escalating doses of gemtuzumab ozogamicin (Mylotarg). Part 1 of the trial evaluates the safety of escalating doses of gemtuzumab ozogamicin and part 2 increases the number of participants.³

Every Patient Is Not the Same

Our efforts to tailor treatment to the individual must also remain a priority. Just 5 years ago, we treated all patients with AML as a relatively homogeneous group. We now understand that there are differences based on molecular profiling. The research of Stone et al revealed that standard chemotherapy with daunorubicin and cytarabine plus the multitargeted kinase inhibitor midostaurin (Rydapt) prolonged overall and event-free survival.⁴

It is through collaboration that we can achieve the most significant gains. Please join us at the Miami Cancer Institute Global Summit on Immunotherapies for Hematologic Malignancies, March 8 to 9, 2024, at the JW Marriott Brickell in Florida.

REFERENCES:

1. O’Reilly RJ, Koehne G, Hasan AN, Doubrovina E, Prockop S. T-cell depleted allogeneic hematopoietic cell transplants as a platform for adoptive therapy with leukemia selective or virus-specific T-cells. Bone Marrow Transplant. 2015;50(suppl 2):S43-S50. doi:10.1038/bmt.2015.95

2. Kosuri S, Adrianzen Herrera D, Scordo M, et al. The impact of toxicities on first-year outcomes after ex vivo CD34+-selected allogeneic hematopoietic cell transplantation in adults with hematologic malignancies. Biol Blood Marrow Transplant. 2017;23(11):2004-2011. doi:10.1016/j.bbmt.2017.07.012

3. Koehne G, Tomlinson B, Suh HC, et al. CD33-deleted hematopoietic stem and progenitor cells display normal engraftment after hematopoietic cell transplant (HCT) and tolerate post-HCT gemtuzumab ozogamicin (GO) without cytopenias. HemaSphere. 2023;7(suppl 3):e24418bc. doi:10.1097/01.HS9.0000972472.24418.bc

4. Stone RM, Mandrekar SJ, Sanford BL, et al. Midostaurin plus chemotherapy for acute myeloid leukemia with a FLT3 mutation. N Engl J Med. 2017;377(5):454-464. doi:10.1056/NEJMoa1614359