In the Journals

Study challenges ‘default use of hypomethylating agents’ in high-risk myelodysplastic syndrome

Amer Zeidan
Amer Zeidan

Older patients with myelodysplastic syndrome appeared more likely to receive persistent treatment with hypomethylating agents under the care of more experienced providers of the agents, according to results of a population-based analysis published in Leukemia & Lymphoma.

Provider experience, however, did not appear to translate into better survival outcomes for these patients.

The findings add to the accumulating body of real-world evidence suggesting suboptimal performance, compared with clinical trial results, of hypomethylating agents among patients with high-risk myelodysplastic syndrome.

“We need to use large database analyses to better understand outcomes in patients with rare cancers, such as high-risk myelodysplastic syndrome, at the level of the community and explore how we can improve those outcomes,” Amer M. Zeidan, MBBS, MHS, assistant professor of medicine at Yale University, told HemOnc Today. “Every patient with high-risk myelodysplastic syndrome should be considered for clinical trials rather than the default use of hypomethylating agents, so that we can make a dent in the natural history of this aggressive cancer.”

Zeidan and colleagues investigated possible associations between provider experience and persistence of hypomethylating agent therapy and improved OS among 2,086 Medicare beneficiaries (median age at diagnosis, 77 years; 63.1% men; 90.4% white) with high-risk myelodysplastic syndrome.

Researchers identified patients using the SEER-Medicare database. They considered the experience of the patients’ 1,142 providers in terms of prior volume of patients with myelodysplastic syndrome, number of patients initiated on hypomethylating agents, or practice in teaching hospitals or cancer centers.

The investigators calculated the number of patients with high-risk myelodysplastic syndrome that the physician encountered or initiated on hypomethylating agent therapy within 2 years before each current patient initiated such therapy.

OS, measured from initiation of hypomethylating agent therapy until death, and persistence of this therapy served as the key outcomes.

Patients received a median of four (IQR, 2-8) hypomethylating agent cycles.

The median myelodysplastic syndrome volume for providers within 2 years was eight patients (interquartile range, 5-13).

Thirty-two percent of patients received treatment from providers who had initiated at least one hypomethylating agent therapy in the previous 2 years. These patients appeared more likely to receive four or more cycles of hypomethylating agents (OR = 1.29; 95% CI, 1.06-1.57).

Median OS among all patients from time of hypomethylating agent initiation was 10 months (95% CI, 10-11; IQR, 4-21). Median 2-year OS was 17.7%.

Results of adjusted analyses showed no significant association between OS and volume of hypomethylating agents administered (HR = 0.93; 95% CI, 0.84-1.03), volume of patients treated for high-risk myelodysplastic syndrome (HR = 0.93; 95% CI, 0.83-1.04) or practice setting.

Researchers noted that the volume measure of the study was restricted to patients with myelodysplastic syndrome and hypomethylating agent initiations in the Medicare fee-for-service population and therefore should be viewed as a relative, but not absolute, measure of provider experience.

“We, along with others, have previously shown that clinical outcomes with hypomethylating agents in the real-life setting for patients with high-risk myelodysplastic syndrome are much worse than observed in the landmark AZA-001 trial, which showed that survival ranged from 11 months to 17 months with the use of hypomethylating agents compared with 24 months with azacitidine,” Zeidan told HemOnc Today. “The reasons for these differences may include better outcomes with highly selected patients enrolled in trials, use of suboptimal schedules of azacitidine and use of decitabine.”

Another possible reason for inferior real-world outcomes is the limited community provider experience in the proper use of hypomethylating agents, as these agents often require multiple cycles to work, are continued despite cytopenias, and require continuation among responding patients, Zeidan said.

“We will continue to look into other factors that might explain the discrepancy between real-life and clinical trial outcomes of patients with high-risk myelodysplastic syndrome who receive hypomethylating agents,” Zeidan told HemOnc Today. – by Jennifer Southall

For more information:

Amer M. Zeidan, MBBS, MHS, can be reached at Yale University School of Medicine, 37 College St., First Floor, New Haven, CT 06510; email: amer.zeidan@yale.edu.

Disclosures: Zeidan reports research funding to his institution from, paid consultant roles with, or travel expenses from AbbVie, Acceleron, ADC Therapeutics, Agios, Ariad, Astellas, BeyondSpring, Boehringer Ingelheim, Cardinal Health, Celgene, Daiichi Sankyo, Incyte, Jazz Pharmaceuticals, MedImmne/AstraZeneca, Novartis, Otsuka, Pfizer, Seattle Genetics, Takeda and Trovagene. Please see the study for all other authors’ relevant financial disclosures.

Amer Zeidan
Amer Zeidan

Older patients with myelodysplastic syndrome appeared more likely to receive persistent treatment with hypomethylating agents under the care of more experienced providers of the agents, according to results of a population-based analysis published in Leukemia & Lymphoma.

Provider experience, however, did not appear to translate into better survival outcomes for these patients.

The findings add to the accumulating body of real-world evidence suggesting suboptimal performance, compared with clinical trial results, of hypomethylating agents among patients with high-risk myelodysplastic syndrome.

“We need to use large database analyses to better understand outcomes in patients with rare cancers, such as high-risk myelodysplastic syndrome, at the level of the community and explore how we can improve those outcomes,” Amer M. Zeidan, MBBS, MHS, assistant professor of medicine at Yale University, told HemOnc Today. “Every patient with high-risk myelodysplastic syndrome should be considered for clinical trials rather than the default use of hypomethylating agents, so that we can make a dent in the natural history of this aggressive cancer.”

Zeidan and colleagues investigated possible associations between provider experience and persistence of hypomethylating agent therapy and improved OS among 2,086 Medicare beneficiaries (median age at diagnosis, 77 years; 63.1% men; 90.4% white) with high-risk myelodysplastic syndrome.

Researchers identified patients using the SEER-Medicare database. They considered the experience of the patients’ 1,142 providers in terms of prior volume of patients with myelodysplastic syndrome, number of patients initiated on hypomethylating agents, or practice in teaching hospitals or cancer centers.

The investigators calculated the number of patients with high-risk myelodysplastic syndrome that the physician encountered or initiated on hypomethylating agent therapy within 2 years before each current patient initiated such therapy.

OS, measured from initiation of hypomethylating agent therapy until death, and persistence of this therapy served as the key outcomes.

Patients received a median of four (IQR, 2-8) hypomethylating agent cycles.

The median myelodysplastic syndrome volume for providers within 2 years was eight patients (interquartile range, 5-13).

Thirty-two percent of patients received treatment from providers who had initiated at least one hypomethylating agent therapy in the previous 2 years. These patients appeared more likely to receive four or more cycles of hypomethylating agents (OR = 1.29; 95% CI, 1.06-1.57).

Median OS among all patients from time of hypomethylating agent initiation was 10 months (95% CI, 10-11; IQR, 4-21). Median 2-year OS was 17.7%.

Results of adjusted analyses showed no significant association between OS and volume of hypomethylating agents administered (HR = 0.93; 95% CI, 0.84-1.03), volume of patients treated for high-risk myelodysplastic syndrome (HR = 0.93; 95% CI, 0.83-1.04) or practice setting.

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Researchers noted that the volume measure of the study was restricted to patients with myelodysplastic syndrome and hypomethylating agent initiations in the Medicare fee-for-service population and therefore should be viewed as a relative, but not absolute, measure of provider experience.

“We, along with others, have previously shown that clinical outcomes with hypomethylating agents in the real-life setting for patients with high-risk myelodysplastic syndrome are much worse than observed in the landmark AZA-001 trial, which showed that survival ranged from 11 months to 17 months with the use of hypomethylating agents compared with 24 months with azacitidine,” Zeidan told HemOnc Today. “The reasons for these differences may include better outcomes with highly selected patients enrolled in trials, use of suboptimal schedules of azacitidine and use of decitabine.”

Another possible reason for inferior real-world outcomes is the limited community provider experience in the proper use of hypomethylating agents, as these agents often require multiple cycles to work, are continued despite cytopenias, and require continuation among responding patients, Zeidan said.

“We will continue to look into other factors that might explain the discrepancy between real-life and clinical trial outcomes of patients with high-risk myelodysplastic syndrome who receive hypomethylating agents,” Zeidan told HemOnc Today. – by Jennifer Southall

For more information:

Amer M. Zeidan, MBBS, MHS, can be reached at Yale University School of Medicine, 37 College St., First Floor, New Haven, CT 06510; email: amer.zeidan@yale.edu.

Disclosures: Zeidan reports research funding to his institution from, paid consultant roles with, or travel expenses from AbbVie, Acceleron, ADC Therapeutics, Agios, Ariad, Astellas, BeyondSpring, Boehringer Ingelheim, Cardinal Health, Celgene, Daiichi Sankyo, Incyte, Jazz Pharmaceuticals, MedImmne/AstraZeneca, Novartis, Otsuka, Pfizer, Seattle Genetics, Takeda and Trovagene. Please see the study for all other authors’ relevant financial disclosures.