Advertisement


Amer Methqal Zeidan, MBBS, MHS, on Myelodysplastic Syndromes: New Data From the IMerge Study of Imetelstat

2023 ASCO Annual Meeting

Advertisement

Amer Methqal Zeidan, MBBS, MHS, of Yale University and Yale Cancer Center, discusses phase III findings on the first-in-class telomerase inhibitor imetelstat, which was given to patients with heavily transfusion-dependent non-del(5q) lower-risk myelodysplastic syndromes that are resistant to erythropoiesis-stimulating agents. Imetelstat resulted in a significant and sustained red blood cell (RBC) transfusion independence in 40% of these heavily transfused patients. The response was also durable and accompanied by an impressive median hemoglobin rise of 3.6 g/dL, and seen in patients with and without ring sideroblasts. Importantly, reduced variant allele frequency was observed in the most commonly mutated myeloid genes which correlated with duration of transfusion independence and hemoglobin rise, therefore suggesting a disease-modifying potential of this agent (Abstract 7004).



Transcript

Disclaimer: This video transcript has not been proofread or edited and may contain errors.
Amer Merthql Zeidan, MBBS, MHS: The IMerge was randomized, placebo-controlled, double-blind study looking at the use of imetelstat versus placebo in patients with lower-risk MDS who were heavily transfusion-dependent after ESA failure, or for patients who are unlikely to respond to ESAs. Imetelstat is a first-in-class direct competitive inhibitor of the telomerase. And preclinical data, as well as early phase-II data suggested very good activity in patients who are transfusion dependent with lower risk MDS. So, the Imerge study was conducted to look at this in a randomized setting where 178 patients who had lower risk MDS by the IPSS with low or intermediate-1 risk groups basically were randomized to receive imetelstat at the standard dose, which is 7.5 milligram per kilogram intravenously every four weeks, or to get a placebo. Those patients had to have more than four units of blood at baseline every eight weeks, so they were very heavily transfusion-dependent. And actually the median transfusion dependency was six units, basically, every eight weeks. The primary endpoint of the study was eight-week transfusion independence. But there were a number of other secondary endpoints that looked at the durability as well as the potential disease modification effect of imetelstat. What we observed in the study is that the study met its primary endpoint. The rate of transfusion independence at eight weeks, basically, for patients who were on the study was 40% with imetelstat, compared to 15% with placebo. And importantly, this was durable, so the median duration of transfusion independence for responders was 52 weeks, compared to 13 weeks. And I think one of the most impressive findings in the study is that the median hemoglobin rise for patients who received imetelstat and responded was 3.6 gram per deciliter. So, those patients went from 8 to more than 11 grams per deciliter of hemoglobin. And this is a very good, impressive rise. It was durable. And as I mentioned, those patients were very heavily transfusion-dependent at baseline. The median transfusion dependency was six units per eight weeks. What we also observed is that there was evidence of disease modification, and that was seen through the reduction in the viable allele frequency of the most commonly mutated genes in patients with MDS, including SF3B1, which also correlated with the duration of transfusion independence and the rise in the hemoglobin. In terms of the side effects, they were expected, along the lines of what we have seen in the phase II. There were basically cytopenias and the cytopenias, however, did not lead to increase in the severe clinical consequences, such as grade 3 or higher bleeding infections or febrile neutropenia. Generally, it was manageable by dose reduction and dose modification interruption. And there were also non-hematologic toxicities, but most of those were lower grade, grade 1 and 2, and also generally reversible by dose modification. So, in general, I think this is a very good option that is leading to sustained and significant increase in the hemoglobin and transfusion independence among lower-risk patients with MDS who had not responded or stopped responding to ESAs, and I hope it's going to be one good option for our patients.

Related Videos

Lymphoma

Tycel J. Phillips, MD, and Alex F. Herrera, MD, on Classical Hodgkin Lymphoma: New Data on Nivolumab, AVD, and Brentuximab Vedotin

Tycel J. Phillips, MD, and Alex F. Herrera, MD, both of the City of Hope National Medical Center, discuss results from the SWOG S1826 study, which showed that nivolumab and AVD (doxorubicin, vinblastine, and dacarbazine) improved progression-free survival vs brentuximab vedotin plus AVD in patients with advanced-stage classical Hodgkin lymphoma. Longer follow-up is needed to assess overall survival and patient-reported outcomes. This trial may be a key step toward harmonizing the pediatric and adult treatment of advanced-stage disease (LBA4).

Lymphoma
Immunotherapy

Tycel J. Phillips, MD, and Swetha Kambhampati, MD, on Mantle Cell Lymphoma: Real-World Outcomes With Brexucabtagene Autoleucel

Tycel J. Phillips, MD, and Swetha Kambhampati, MD, both of City of Hope National Medical Center, discuss new findings showing that the real-world effectiveness and safety of brexucabtagene autoleucel were similar to data from the pivotal ZUMA-2 trial in patients with relapsed or refractory mantle cell lymphoma, regardless of prior BTK inhibition, bendamustine, or autologous stem cell transplantation (Abstract 7507).

Skin Cancer

Allison Betof Warner, MD, PhD, and Zeynep Eroglu, MD, on Metastatic Melanoma: New Data on Dabrafenib, Trametinib, and Navitoclax

Allison Betof Warner, MD, PhD, of Stanford University Medical Center, and Zeynep Eroglu, MD, of H. Lee Moffitt Cancer Center and Research Institute, discusses phase II findings showing that in patients with BRAF-mutant metastatic melanoma, dabrafenib plus trametinib and navitoclax (DTN) was associated with a complete response rate of 20% and an overall response rate of 84%. Additionally, there was a trend toward improved overall survival in patients treated with DTN compared with dabrafenib plus trametinib alone; the difference in overall survival was more pronounced in patients with a smaller tumor burden (Abstract 9511).

Bladder Cancer

Enrique Grande, MD, on Metastatic Urothelial Carcinoma: Updated Data From IMvigor130

Enrique Grande, MD, of The University of Texas MD Anderson Cancer Center, discusses new findings that show initial responses to induction therapy with atezolizumab plus platinum and gemcitabine did not seem to impact overall survival for patients with metastatic urothelial carcinoma. Cisplatin-treated patients appeared to derive a greater benefit with atezolizumab than did carboplatin-treated patients (Abstract 4503).

Prostate Cancer

Alicia K. Morgans, MD, MPH, and Karim Fizazi, MD, on Prostate Cancer: Phase III Results on Talazoparib Plus Enzalutamide as First-Line Treatment

Alicia K. Morgans, MD, MPH, of Dana-Farber Cancer Institute, and Karim Fizazi, MD, of Institut Gustave Roussy, University of Paris-Saclay, discuss findings from the TALAPRO-2 study, which showed that talazoparib plus enzalutamide improved radiographic progression–free survival over standard-of-care enzalutamide as first-line treatment for patients with metastatic castration-resistant prostate cancer and HRR gene alterations. This regimen also delayed the time to deterioration in global health status and quality of life (Abstract 5004).

Advertisement

Advertisement




Advertisement