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Sagar Lonial on SOHO 2020
President and chair of the SOHO 2020 virtual meeting, Sagar Lonial of Winship Cancer Insitute of Emory University, discusses what to expect from the 8th Annual Society of Hematologic Oncology (SOHO) educational, research-led virtual meeting.
Gilteritinib in relapsed/refractory AML
Gilteritinib is a second-generation, oral, FMS-like tyrosine kinase-3 (FLT3) inhibitor that has shown single-agent activity in relapsed/refractory FLT3-mutated acute myeloid leukemia (AML).
In this video, Naval Daver, of the University of Texas MD Anderson Cancer Center, outlines the use of gilteritinib in relapsed/refractory FLT3 mutated AML patients, highlighting the significantly longer survival and higher percentages of patients in remission when compared to salvage therapy as evaluated in the ADMIRAL study (NCT02421939).1
Dr Daver highlights novel combinations using gilteritinib and hypomethylating agents currently undergoing investigation with the aim of curing the disease, including the ongoing LACEWING trial (NCT02752035) comparing gilteritinib alone, against gilteritinib and azacitidine in chemotherapy ineligible FLT3 mutated AML patients.
Chemo-free regimens in follicular lymphoma
Follicular lymphoma (FL) is a disease with a high remission duration in the first line, with 80% of patients having an overall survival of >10 years following diagnosis.2 Therefore, the treatment of FL with therapies that result in fewer toxicities than those associated with chemotherapy is crucial in order to reduce the negative impact on quality of life of patients with lymphoma.
In this discussion, Loretta Nastoupil of the University of Texas MD Anderson Cancer Center discusses chemotherapy-free regimens in lymphoma including lenalidomide based approaches, and the recent approval of tazemetostat, an EZH2 inhibitor, in relapsed/refractory follicular lymphoma.
Immunotherapy for T-cell malignancies
The challenges associated with CAR T-cell therapies for T-cell malignancies are due to molecular targets being present within the T-cell malignancy as well as the effector T-cell, resulting in fratricide.3
The different approaches investigated to prevent fratricide in T-cell malignancies are discussed by John DiPersio of Washington University who outlines the use of CRISPR-mediated gene editing to remove the T-cell receptor and produce an off-the-shelf CAR T-cell construct whilst preventing contamination of malignant cells that phenotypically resemble healthy T-cells.
Changing treatment landscape of relapsed/refractory myeloma
The landscape of relapsed or refractory multiple myeloma is constantly evolving and many new therapies have been approved by the United States FDA for these patients.
In this video, Joshua Richter of Mount Sinai Medical Center outlines new treatment approaches for relapsed/refractory patients, including the recent approval of belantamab mafodotin, the antibody-drug conjugate, based on the results of the Phase II DREAMM-2 study (NCT03525678)4, as well as results of the HORIZON (NCT02963493)5 and OCEAN (NCT03151811) studies, investigating melflufen, a peptidase enhanced cytotoxic agent, in this indication. The potential for next-generation IMiDs such as iberdomide in relapsed/refractory multiple myeloma patients is also discussed.
Targeting BCL-2 in MDS
BCL-2 is a regulator of apoptosis and has clinical significance is several hematological malignancies. In this video, Amer Zeidan, of Yale University and Yale Cancer Center outlines BCL-2 targeting agents currently under investigation in the treatment of myelodysplastic syndromes (MDS) in combination with hypomethylating agents (HMA) such as azacitidine and decitabine and highlights the importance of new therapies in patients who have failed HMA monotherapy.
Dr Zeidan also discusses the recent approvals of luspatercept for low-risk MDS as well as an orally available decitabine as landmark advances in the treatment and management of MDS. Results of clinical trials evaluating venetoclax, in combination with azacitidine are also explored by Dr Zeidan as well as crucial next steps in MDS such as the importance of predicting response, mitigating resistance, and how to combine oral therapies.
ZUMA-1: outcomes of CAR-T in older patients
The Phase I/II ZUMA-1 study (NCT02348216) evaluated the safety and efficacy of the CAR-T construct, axicabtagene ciloleucel in patients with refractory aggressive non-Hodgkin lymphoma.
In this video, Sattva Neelapu, of the University of Texas MD Anderson Cancer Center outlines the outcomes of the ZUMA-1 study in patients 65 years or older, and highlights the favorable safety and efficacy profile in this patient population.7
References
- Perl A, Martinelli G, Cortes J et al. Gilteritinib or Chemotherapy for Relapsed or Refractory FLT3-Mutated AML. New England Journal of Medicine. 2019;381(18):1728-1740.
- Carbone A, Roulland S, Gloghini A et al. Follicular lymphoma. Nature Reviews Disease Primers. 2019;5(1).
- DiPersio J, Staser K, Cooper M. Immunotherapy for T-Cell ALL and T-Cell NHL. Clinical Lymphoma Myeloma and Leukemia. 2020;20:S56-S58.
- Lonial S, Lee H, Badros A et al. Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomised, open-label, phase 2 study. The Lancet Oncology. 2020;21(2):207-221.
- Richardson P, Oriol A, Larocca A et al. HORIZON (OP-106) Study of Melflufen in Patients with Relapsed/Refractory Multiple Myeloma (RRMM) Refractory to Daratumumab and/or Pomalidomide: Updated Efficacy and Safety. Clinical Lymphoma Myeloma and Leukemia. 2019;19:S329-S330.
- Schjesvold F, Robak P, Pour L et al. OCEAN: a randomized Phase III study of melflufen + dexamethasone to treat relapsed refractory multiple myeloma. Future Oncology. 2020;16(11):631-641.
- Neelapu S, Jacobson C, Oluwole O et al. Outcomes of older patients in ZUMA-1, a pivotal study of axicabtagene ciloleucel in refractory large B-cell lymphoma. Blood. 2020;135(23):2106-2109.
