Prapti Patel, MD, assistant professor in the Department of Internal Medicine at Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, discusses the clinical implications of the FDA approval of luspatercept-aamt (Reblozyl) in myelodysplastic syndrome (MDS).

On April 3, 2020, the FDA approved luspatercept for the treatment of anemia failing an erythropoiesis stimulating agent (ESA) and requiring 2 or more red blood cell units over 8 weeks in adult patients with very low- to intermediate-risk MDS with ring sideroblasts or with MDS/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis.

Prior to the approval, there were no alternative options available for patients who progressed on ESAs other than chemotherapy, explains Patel.

While decitabine and azacitidine are considered “lite” or low-dose chemotherapies, they are associated with significant morbidity and mortality, says Patel.

Though patients with low-risk disease have a 7- to 10-year survival rate, they often have a poor quality of life due to transfusion dependence, explains Patel. As such, luspatercept should be considered for these patients.

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Prapti Patel, MD, discusses the clinical implications of the FDA approval of luspatercept-aamt in myelodysplastic syndrome.



Dr. Patel on the Clinical Implications of Luspatercept Approval in MDS

Prapti Patel, MD, assistant professor in the Department of Internal Medicine at Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, discusses the clinical implications of the FDA approval of luspatercept-aamt (Reblozyl) in myelodysplastic syndrome (MDS).

On April 3, 2020, the FDA approved luspatercept for the treatment of anemia failing an erythropoiesis stimulating agent (ESA) and requiring 2 or more red blood cell units over 8 weeks in adult patients with very low- to intermediate-risk MDS with ring sideroblasts or with MDS/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis.

Prior to the approval, there were no alternative options available for patients who progressed on ESAs other than chemotherapy, explains Patel.

While decitabine and azacitidine are considered “lite” or low-dose chemotherapies, they are associated with significant morbidity and mortality, says Patel.

Though patients with low-risk disease have a 7- to 10-year survival rate, they often have a poor quality of life due to transfusion dependence, explains Patel. As such, luspatercept should be considered for these patients.

Prapti Patel, MD, discusses the clinical implications of the FDA approval of luspatercept-aamt in myelodysplastic syndrome.

Prapti Patel, MD, assistant professor in the Department of Internal Medicine at Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, discusses data from the MEDALIST trial on the use of luspatercept-aamt (Reblozyl) in patients with low-risk myelodysplastic syndromes (MDS).

Data from the phase II trial showed that patients with low-risk MDS that were refractory to erythroid-stimulating agents (ESAs) had a response to luspatercept and became transfusion independent within 8 to 12 weeks, says Patel. Patients who had ring sideroblasts did better with the treatment, adds Patel.

Specifically, transfusion independence (TI) for ≥8 weeks was observed in 38% of the patients in the luspatercept group compared with 13% in the placebo group (

 <.001). A higher percentage of patients in the luspatercept group than in the placebo group met the key secondary end point of TI for ≥12 weeks (28% vs 8% for weeks 1-24, and 33% vs 12% for weeks 1-48; 

When looking at the longer-term data of the trial, investigators noted a percentage of patients who needed to undergo transfusions again, says Patel, a finding that was concerning. The next step for this research is to identify new drugs that can provide patients with a longer period of TI, says Patel. One such drug that is being evaluated at UT Southwestern is imetelstat.

Trials are examining imetelstat in patients with MDS who are refractory to ESAs; the hope is that these patients will experience long-term TI for those patients, concludes Patel.

Prapti Patel, MD, discusses data from the MEDALIST trial on the use of luspatercept-aamt in patients with low-risk myelodysplastic syndromes.

Dr. Patel on Data From the MEDALIST Trial in Low-Risk MDS

Prapti Patel, MD, assistant professor, Department of Internal Medicine, Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, discusses the unmet need of FLT3 inhibitors in the treatment of patients with acute myeloid leukemia (AML).

There is a lot of space for FLT3 inhibitors in AML because a long-term care has not been found, says Patel. When looking at the tail of the survival curves for any FLT3 inhibitors, they taper off and there are no long-term survivors. These inhibitors should be looked at upfront, Patel adds.

A large concern is for a subgroup of patients that are resistant to FLT3 inhibitors. For example, patients who have a 

 pathway mutation tend to be resistant to gilteritinib (Xospata) or other FLT3 inhibitors. Novel agents have that space to fill, concludes Patel.

Prapti Patel, MD, discusses the unmet need of FLT3 inhibitors in the treatment of patients with acute myeloid leukemia.
 

Dr. Patel on the Unmet Need of FLT3 Inhibitors in AML Treatment

Prapti Patel, MD, assistant professor, Department of Internal Medicine, Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, discusses the role of gilteritinib (Xospata) in patients with 

Preliminary data for gilteritinib presented at the 2019 AACR Annual Meeting looked at patients with 

 mutations, who were randomized 2:1 to receive gilteritinib alone versus chemotherapy, explains Patel. Patients were permitted to go onto transplant and, if randomized to the gilteritinib arm, were also allowed to receive maintenance gilteritinib therapy afterward. The response rates in patients receiving gilteritinib doubled compared with patients receiving chemotherapy alone, indicating gilteritinib, an oral targeted therapy, as the superior option for this patient population, according to Patel.

Gilteritinib is less toxic than chemotherapy because it is targeted, says Patel. Patients who underwent transplant were treated with a targeted therapy that was not as toxic, and were therefore more fit to undergo transplant. As a result, they were able to tolerate the transplant better and have an option for maintenance therapy to prevent relapse after transplant, which is a concern for patients with aggressive 

Prapti Patel, MD, discusses the role of gilteritinib in patients with FLT3-mutated acute myeloid leukemia.

Dr. Patel on the Role of Gilteritinib in FLT3+ AML

Prapti Patel, MD, assistant professor, Department of Internal Medicine, Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, discusses delaying treatment until after genetic testing in elderly patients with newly diagnosed acute myeloid leukemia (AML).

Currently, there are limited treatment options for this patient population, says Patel. Often, these patients cannot achieve remissions with the currently available treatment options, or the therapies are too toxic.

Generally, patients with leukemia begin chemotherapy within 72 hours of diagnosis, says Patel. However, emerging evidence suggests patients may benefit from delaying therapy until after receiving genetic testing results.

The Beat AML Master Trial (NCT03013998) was designed to identify safer and more effective novel therapies for patients with AML, explains Patel. According to an analysis of elderly patients in the Beat AML Master study, it is safe to withhold treatment for 7 days while awaiting germline test results. Moreover, the patients who were treated on the trial did very well compared with those who received standard of care chemotherapy, concludes Patel.

Prapti Patel, MD, discusses delaying treatment until after genetic testing in elderly patients with newly diagnosed acute myeloid leukemia.

Prapti Patel, MD

Articles

Dr. Patel on the Clinical Implications of Luspatercept Approval in MDS

Dr. Patel on the Clinical Implications of Luspatercept Approval in MDS

Dr. Patel on Data From the MEDALIST Trial in Low-Risk MDS

Dr. Patel on the Unmet Need of FLT3 Inhibitors in AML Treatment

Dr. Patel on the Role of Gilteritinib in FLT3+ AML

Dr. Patel on Delaying Treatment for Elderly Patients With Newly Diagnosed AML