Farhad Ravandi-Kashani, MD, Janiece and Stephen A. Lasher Professor of Medicine, chief, Section of Developmental Therapeutics, professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the FDA approval of luspatercept-aamt (Reblozyl) in myelodysplastic syndrome (MDS).

the FDA approved luspatercept for the treatment of

 with erythropoiesis-Stimulating Agent (ESA)–naïve very low– to intermediate-risk MDS who may require regular red blood cell (RBC) transfusions. The regulatory decision was supported by data from the phase 3 COMMANDS trial (NCT03682536). The open-label, randomized study investigated the use of luspatercept vs the ESA epoetin alfa. Luspatercept was shown to produce superior RBC transfusion independence (RBC-TI) and hemoglobin (Hb) increase vs epoetin alfa.

, Guillermo Garcia-Manero, MD, of MD Anderson Cancer Center, presented data from the phase 3 trial, showing that the study met its primary end point of RBC-TI. Of the patients (n = 178) who were treated with luspatercept, 58.5% remained RBC-TI for 12 weeks or more with a concurrent mean hemoglobin increase of at least 1.5 g/dL, compared with 31.2% of patients treated with the ESA epoetin alfa (n = 178; 

Anemia and transfusion dependence has been one of the biggest challenges issues associated with the use of ESAs in this patient population. Although they are considered standard treatment, Ravandi-Kashani explains, ESAs have limited efficacy. Therefore, having a new agent with a different mechanism of action that can elicit significant improvement in RBC-TI is an important step forward in this space, Ravandi-Kashani emphasizes. The COMMANDS trial demonstrated that luspatercept can be superior to ESAs in the frontline for in this subset of patients, he concludes.

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Farhad Ravandi-Kashani, MD, discusses the FDA approval of luspatercept in myelodysplastic syndrome.

Dr Ravandi-Kashani on the FDA Approval of Luspatercept in MDS

Farhad Ravandi, MBBS, professor of medicine, department of leukemia, The University of Texas MD Anderson Cancer Center, discusses targeting CD33 in patients with relapsed/refractory acute myeloid leukemia (AML).

Considering recent FDA approvals, patients with relapsed/refractory AML still have limited treatment options, Ravandi says. CD33 is expressed by virtually all patients with AML, making it a somewhat universal target. Bispecific antibodies have shown impact in relapsed/refractory acute lymphocytic leukemia, giving investigators the idea that this class of agents may work in AML as well.

Findings from a phase I study of the anti-CD33 bispecific T-cell engager antibody construct AMG 330 were presented at the 2018 ASH Annual Meeting. Patients enrolled on this trial had relapsed/refractory AML with >5% blasts in their bone marrow. Responses were observed in 5 out of 40 patients. These responses consisted of 2 complete responses (CRs), 2 CRs with incomplete count recovery, and 1 morphologic leukemia-free state.

Farhad Ravandi, MBBS, professor of medicine, department of leukemia, The University of Texas MD Anderson Cancer Center, discusses targeting CD33 in patients with relapsed/refractory acute myeloid leukemia.

Dr. Ravandi on Targeting CD33 in Relapsed/Refractory AML

Farhad Ravandi-Kashani, MD, professor, Department of Leukemia, The University of Texas MD Anderson Cancer Center, discusses vadastuximab talirine plus hypomethylating agents (HMA) in acute myeloid leukemia (AML).

The CD33-directed antibody-drug conjugate vadastuximab talirine showed good tolerability in a phase I single-agent trial, says Ravandi, with the only toxicity being myelosuppression.

This led to a trial combining low doses of vadastuximab talirine with HMA, given on the last day of therapy with either azacitidine or decitabine.

Farhad Ravandi-Kashani, MD, professor, Department of Leukemia, The University of Texas MD Anderson Cancer Center, discusses vadastuximab talirine plus hypomethylating agents in acute myeloid leukemia.

Farhad Ravandi-Kashani, MD

Articles

Dr Ravandi-Kashani on the FDA Approval of Luspatercept in MDS

Dr. Ravandi on Targeting CD33 in Relapsed/Refractory AML

Dr. Ravandi on Vadastuximab Talirine Plus Hypomethylating Agents in AML