Response to hypomethylating agents may not predict survival after HSCT for AML
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ORLANDO — Patients with acute myeloid leukemia who failed to achieve complete remission with hypomethylating agent-based therapy still had favorable survival outcomes after hematopoietic stem cell transplantation, according to study results presented at TCT | Transplantation & Cellular Therapy Meetings.
The results suggested traditional response categories may not predict survival as reliably in the setting of hypomethylating agent-based therapy as they do with intensive chemotherapy before HSCT, Brittany K. Ragon, MD, leukemia transplant specialist in the department of hematologic oncology and blood disorders at Levine Cancer Institute at Atrium Health, and colleagues concluded.
“No matter how these patients were classified, if they received a hypomethylating agent and followed that with transplant, survival was actually quite good,” Ragon told Healio. “OS was almost 50% after 3 years of follow-up, which is very good, especially considering adverse-risk patients were included.”
The hypomethylating agents azacitidine and decitabine are standard therapies for older patients with AML, and they also appear promising for patients with favorable-risk disease, including NPM1-mutated AML.
Prior studies suggested hypomethylating agent-based therapy can be used as a bridge to potentially curative allogeneic HSCT for AML.
Analyses of the correlation between traditional treatment response categories and survival historically have been performed in the setting of intensive therapy rather than in the context of newer or less intense regimens.
Ragon and colleagues hypothesized that traditional response criteria may not predict outcomes as reliably in the setting of nonintensive chemotherapy and subsequent HSCT.
The investigators conducted their study to assess the correlation of response to hypomethylating agent-based therapy with survival among patients with AML who underwent subsequent HSCT.
The analysis included all patients with AML who underwent HSCT after frontline or salvage hypomethylating agent-based therapy at Levine Cancer Institute from June 2015 through May 2019.
Researchers categorized responses prior to HSCT as morphologic complete remission, complete remission with incomplete hematologic recovery, morphologic leukemia-free state or refractory.
Investigators used flow cytometry and/or molecular testing to evaluate minimal residual disease (MRD) status.
The analysis included 37 patients (median age at HSCT, 64 years; range, 28-80; 62% men). At diagnosis, 22% had favorable-risk disease per National Comprehensive Cancer Network criteria, 43% had intermediate-risk disease and 35% had unfavorable-risk disease.
Researchers reported the following mutation prevalence: FLT3-internal tandem duplication (22%), NPM1 (16%), TP53 (13%) and FLT-tyrosine kinase domain (3%).
All 37 patients received hypomethylating agents; 19 received them in the frontline setting.
The majority (73%) received azacitidine, 16% received decitabine, and 11% received azacitidine followed by decitabine. Twenty-three patients (62%) received hypomethylating agent monotherapy, and 14 (38%) received concomitant venetoclax (Venclexta; AbbVie, Genentech), sorafenib (Nexavar, Bayer), lenalidomide (Revlimid, Celgene) or midostaurin.
About one-third (32%) of patients achieved complete remission prior to HSCT, 30% achieved complete remission with incomplete hematologic recovery, 30% achieved morphologic complete remission and 8% were refractory.
Seventeen of 34 patients evaluated for MRD achieved MRD-negative status.
Median follow-up after HSCT for the entire cohort was 16 months.
Results from the entire cohort showed median OS of 35.7 months; 85% of patients remained alive at 1 year and 61% survived at least 2 years.
Patients who achieved complete remission or complete remission with incomplete hematologic recovery demonstrated no statistically significant advantage in OS (HR = 2.11; 95% CI, 0.63-7.01; 2-year OS, 57% vs. 65%) or RFS (HR = 1.15; 95% CI, 0.41-3.25; 2-year RFS, 52% vs. 53%) compared with those classified as morphologic leukemia-free state or refractory.
Patients with MRD positivity achieved shorter OS (HR = 2.61; 95% CI, 0.79-12.11; 2-year OS, 58% vs. 79%) and RFS (HR = 1.15; 95% CI, 0.41-3.25; 2-year RFS, 35% vs. 72%) than MRD-negative patients. Although the differences did not reach statistical significance, the results suggest that survival outcomes are not as favorable for patients with minimal residual disease positivity regardless of response, Ragon said.
“The take-home message from this study is to try not to focus too much on the response,” Ragon told Healio. “Treat the patient, be patient with hypomethylating agents and consider taking patients to transplant when you have some type of response. Don’t let morphologic leukemia-free state keep you from taking a patient to transplant.” – by Mark Leiser
Reference: Ragon BK, et al. Abstract 132. Presented at: TCT | Transplantation & Cellular Therapy Meetings; Feb. 19-23, 2020; Orlando.
Disclosures: Ragon reports no relevant financial disclosures. Please see the abstract for all other authors’ relevant financial disclosures.