Alison R. Sehgal, MD, assistant professor of medicine, hematologist/medical oncologist, University of Pittsburgh School of Medicine, University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center, discusses key targetable alterations in 

 mutations are important targetable alterations in AML​. Moreover, the targeted therapies ivosidenib (Tibsovo), an IDH1 inhibitor and enasidenib (Idhifa), an IDH2 inhibitor ​are approved for use in patients with AML. Further evaluation of these therapies ​is planned to determine whether combination strategies could be more beneficial to patients, Sehgal says.

Additionally, gilteritinib (Xospata), a FLT3 inhibitor​, received regulatory approval in Novembe​r 2018 for ​the treatment of adult patients with relapsed/refractory AML, who harbor 

 mutations, as detected by an FDA-approved test. Like ivosidenib and enasidenib, gilteritinib is undergoing further testing to determine if it is more effective when used in combination ​regimens. ​Additionally, data are emerging regarding the role of gilteritinib in the pre- and post-transplant settings ​for patients with AML, Sehgal adds.

 represents an unmet need in the AML space; however, ongoing research efforts are evaluating different therapies that may yield a survival advantage in patients who harbor 

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Alison R. Sehgal, MD, discusses key targetable alterations in acute myeloid leukemia. 

Dr. Sehgal on Key Targetable Alterations in AML

Alison R. Sehgal, MD, assistant professor of medicine, hematologist/medical oncologist, University of Pittsburgh School of Medicine, UPMC Hillman Cancer Center, discusses the clinical implications of CAR T-cell therapy in diffuse large B-cell lymphoma (DLBCL).

The approvals of axicabtagene ciloleucel (axi-cel; Yescarta) and tisagenlecleucel (Kymriah) have altered the paradigms of relapsed/refractory non-Hodgkin lymphoma and relapsed/refractory DLBCL, respectively. Specifically, these agents have changed the way treatment is approached for patients with DLBCL, says Sehgal. This is particularly true for patients who relapse after autologous stem cell transplant (ASCT), have resistant disease, and those who can’t achieve a remission to even proceed with ASCT, she adds.

Instead of looking to palliative care when patients relapse, patients who are fit enough may instead be able to receive CAR T-cell therapy. Currently, CAR T-cell therapy is not curative, although the goal is to achieve a curative approach, says Sehgal. Therefore, the field is focused on bringing intensive therapy that could lead to long-term remission to patients.

Dr. Sehgal on the Clinical Implications of CAR T-Cell Therapy in DLBCL

Alison R. Sehgal, MD, assistant professor of medicine, hematologist/medical oncologist, University of Pittsburgh School of Medicine, UPMC Hillman Cancer Center, discusses ways to manage cytokine release syndrome (CRS) and neurotoxicity associated with CAR T-cell therapy.

The management strategies for CRS and neurotoxicity depend on the severity of the syndromes, says Sehgal. With regard to CRS experienced with axicabtagene-ciloleucel (axi-cel; Yescarta), most patients get a fever, which is classified as grade 1. These patients can be managed supportively most of the time—often with Tylenol, fluids, or other antipyretics. If the fever continues, or if it escalates to hypotension or organ dysfunction&mdash;particularly pulmonary dysfunction&mdash;then an interleukin-6 receptor blocker is often used.

If a patient develops CRS that is refractory to supportive care and tocilizumab (Actemra), many centers, in accordance with real-world data, rely on steroids to combat the toxicity. Tocilizumab does not have a role in the management of neurologic toxicity unless there is concurrent CRS. Therefore, patients who develop more severe neurologic toxicity should be moved swiftly to steroids, concludes Sehgal.

Alison R. Sehgal, MD

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Dr. Sehgal on Key Targetable Alterations in AML

Dr. Sehgal on the Clinical Implications of CAR T-Cell Therapy in DLBCL

Dr. Sehgal on Managing CRS and Neurotoxicity From CAR T-Cell Therapy