Dr Koehne on the Use of Chemotherapy-Only Conditioning Regimens in Hematologic Malignancies

Guenther Koehne, MD, PhD, deputy director, chief, Blood and Marrow Transplant, Hematologic Oncology, Benign Hematology, Miami Cancer Institute, Baptist Health, discusses the advantages of using chemotherapy-only conditioning regimens for patients with hematologic malignancies undergoing allogeneic stem cell transplantation.

The administration of conditioning regimens prior to allogeneic donor-derived stem cell transplantation significantly impacts post-transplant outcomes in patients with hematologic malignancies, Koehne begins. Traditionally, the standard conditioning regimen involved high doses of total body irradiation combined with chemotherapy, aimed at eliminating the patient's immune system and bone marrow function to facilitate successful engraftment and immune reconstitution from the donor stem cells, Koehne explains. However, this approach is associated with a substantial adverse effect (AE) profile, including mucositis, infertility, and other complications associated with high-dose radiation, he says.

Koehne states that there has been a shift in understanding whether total body irradiation is necessary for all patients requiring stem cell transplantation across various malignancies. Research in certain tumor types, such as acute myeloid leukemia and myeloproliferative syndromes, has shown that chemotherapy-only conditioning regimens can be highly effective and sufficient for achieving successful transplantation outcomes, he expands. Importantly, these chemotherapy-only regimens are associated with fewer AEs and better patient tolerance compared with regimens that include total body irradiation, Koehne notes.

The use of chemotherapy-only conditioning regimens has also expanded the eligibility criteria for allogeneic stem cell transplantation, Koehne continues. By shifting away from total body irradiation and utilizing chemotherapy-only conditioning regimens, transplant physicians are able to optimize patient outcomes while minimizing treatment-related toxicity, Koehne states. This advancement has not only improved the safety and tolerability of stem cell transplantation but has also expanded access to this potentially curative treatment option for a broader range of patients, including those previously considered too frail or elderly for conventional conditioning approaches, he concludes.

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Guenther Koehne, MD, PhD, discusses the use of chemotherapy-only conditioning regimens for patients with hematologic malignancies undergoing transplant.

Guenther Koehne, MD, PhD, discusses research efforts to overcome resistance to CAR T-cell therapy in hematologic malignancies.

Dr Koehne on Efforts to Overcome CAR T-Cell Resistance in Hematologic Malignancies

Guenther Koehne, MD, PhD, deputy director, chief, Blood and Marrow Transplant, Hematologic Oncology, Benign Hematology, Miami Cancer Institute, Baptist Health, discusses the continued exploration of novel approaches that are taking place to overcome resistance mechanisms in hematologic malignancies, specifically in patients who may not respond optimally to initial CAR T-cell treatment.

Resistance to CAR T-cell therapies may arise from several factors, including insufficient expression of target molecules on tumor cells and mechanisms allowing tumors to evade immune detection, such as downregulation of targeted antigens, Koehne begins. These challenges can lead to disease recurrence without the expression of the originally targeted marker, he adds.

To address these issues, researchers are exploring innovative strategies to enhance the efficacy of CAR T-cell therapies, Koehne states. One promising approach involves the use of bispecific CAR T-cells, which simultaneously target multiple antigens on cancer cells, Koehne details. For example, an ongoing clinical trial led by Dr. Koehne and his colleagues at the Miami Cancer Institute is investigating CAR T-cell therapy targeting both CD19 and CD20 or CD19 and CD22 in lymphoma.

By targeting multiple antigens on tumor cells, bispecific CAR T-cells aim to overcome resistance mechanisms and reduce the risk of disease recurrence in early stages of disease, Koehne notes. This strategy offers a more comprehensive approach to tumor targeting, potentially enhancing therapeutic responses and prolonging remission in patients with hematologic malignancies, he emphasizes.

Overall, the development of bispecific CAR T-cell therapy may represent the next generation of CAR T-cell therapies, offering the potential to overcome resistance and improve treatment outcomes. Continued research in this area is crucial to optimize CAR T-cell therapies and broaden their applicability across various cancer types. With further investigation and refinement, bispecific CAR T-cells may become an integral component of personalized cancer treatment strategies, ultimately benefiting patients with resistant or recurrent disease, Koehne concludes.

Guenther Koehne, MD, PhD, deputy director and chief of stem cell transplantation, hematologic oncology and benign hematology at Miami Cancer Institute, discusses the real-life study of CAR T-cell agents axicabtagene ciloleucel (axi-cel; Yescarta) vs tisagenlecleucel (tisa-cel; Kymriah) in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

 produced plenty of intrigue around CAR T-cell agents, according to Koehne. One analysis of particular interest was a propensity score–matched comparison from the French DESCAR-T registry (NCT04328298) of axi-cel and tisa-cel in patients with relapsed or refractory DLBCL, Koehne says. It is unknown how all CAR T-cell therapies definitively measure up against one another, Koehne adds. 

Data from the randomized study showed that axi-cel elicited higher response rates in this population; however, the product was also associated with a higher rate of adverse effects, such as immune effector cell–associated neurotoxicity syndrome and cytokine release syndrome, when compared with tisa-cel, Koehne explains. Furthermore, axi-cel and tisa-cel produced similar overall survival rates, raising questions about how to optimally choose between the 2 therapies, Koehne says. 

However, potential strategies may be able to inform which products to use in different patient populations, Koehne adds. For example, tisa-cel could be a strong option for older patients with more comorbidities, and axi-cel might be ideal for younger patients with less aggressive lymphomas, Koehne concludes. 

Guenther Koehne, MD, PhD, discusses the real-life study of CAR T-cell agents axicabtagene ciloleucel vs tisagenlecleucel in patients with relapsed or refractory diffuse large B-cell lymphoma.

Guenther Koehne, MD, PhD

Articles

Dr Koehne on the Use of Chemotherapy-Only Conditioning Regimens in Hematologic Malignancies

Dr Koehne on Efforts to Overcome CAR T-Cell Resistance in Hematologic Malignancies

Dr. Koehne on Axi-Cel Vs Tisa-Cel in Relapsed/Refractory Diffuse Large B-Cell Lymphoma