[Interview] Vanflyta reshapes FLT3-ITD AML care beyond the transplant-cen...

Treatment strategies for FLT3-ITD-mutated acute myeloid leukemia (AML) are evolving beyond the traditional paradigm centered on intensive chemotherapy and hematopoietic stem cell transplantation (HSCT). Increasingly, clinicians are refining treatment approaches based on measurable residual disease (MRD) assessment and incorporating maintenance therapy into long-term disease management.

At the center of this shift is Vanflyta (quizartinib), a next-generation FLT3 inhibitor recently approved in Korea. By extending treatment beyond induction and consolidation chemotherapy into maintenance therapy, Vanflyta has demonstrated the potential to improve survival outcomes and raised a new question in FLT3-ITD AML care: Do all patients still need to proceed to stem cell transplantation?

Experts caution, however, that the emergence of Vanflyta should not immediately be interpreted as a replacement for transplantation. HSCT remains a critical treatment strategy for AML patients at high risk of relapse. Still, they noted that if clinicians can comprehensively evaluate MRD status, co-occurring genetic mutations, and transplant eligibility, some patients may be candidates for a new treatment pathway built around quizartinib maintenance therapy.

Korea Biomedical Review spoke with Professor Cheong June-won of the Department of Hematology at Severance Hospital and Professor Xavier Cheng-Hong Tsai of the Department of Hematology at National Taiwan University Hospital discussed the changing FLT3-ITD AML treatment landscape, the clinical significance of Vanflyta, and differences in treatment accessibility between Korea and Taiwan.

Professor Cheong June-won of Severance Hospital (left) and Professor Xavier Cheng-Hong Tsai of National Taiwan University Hospital discussed the latest trends in FLT3-ITD AML treatment, focusing on the arrival of Vanflyta, during an interview with Korea Biomedical Review. (KBR photo)

FLT3-ITD is no longer viewed solely as a 'high-risk' mutation

FLT3-ITD is one of the most common genetic mutations identified in AML. Long associated with poor prognosis and high relapse risk, the mutation is now being reassessed as targeted therapies expand and risk classification systems become more refined.

“FLT3-ITD mutations were initially considered high-risk, but the current European LeukemiaNet (ELN) guidelines classify them as intermediate-risk rather than adverse-risk,” Professor Cheong said.

Still, he emphasized that the revised classification does not diminish the mutation’s clinical significance.

“Rather than saying FLT3-ITD is no longer high-risk, it is more appropriate to view these patients as having relatively poor prognoses even within the intermediate-risk category,” he explained. “Because intermediate-risk AML includes a highly heterogeneous patient population, FLT3-ITD patients remain candidates for more aggressive treatment strategies.”

Current treatment for FLT3-mutated AML generally begins with intensive remission induction therapy. According to Professor Cheong, Korean clinical practice typically involves explaining treatment options to patients, combining the standard 7+3 chemotherapy regimen with the FLT3 inhibitor midostaurin, followed by consolidation therapy and HSCT whenever feasible.

“At this point, chemotherapy alone is still insufficient to achieve optimal outcomes, so we continue to consider stem cell transplantation whenever possible,” he said.

Taiwan follows a broadly similar approach to treatment. Professor Tsai said, "Because midostaurin is reimbursed in Taiwan, younger patients who can tolerate intensive chemotherapy generally receive midostaurin in combination with induction therapy, followed by consolidation and transplantation."

However, he noted that treatment strategies have begun to evolve since the introduction of Vanflyta.

“In the past, FLT3-ITD mutations were viewed as extremely poor prognostic markers,” Professor Tsai said. “Now, emerging data suggest that favorable outcomes may be achievable with appropriate maintenance therapy. The treatment paradigm is changing.”

In other words, FLT3-ITD is no longer seen solely as a "marker of poor prognosis." While relapse risk remains an important concern, the mutation is increasingly regarded as a treatable therapeutic target through the use of targeted agents and maintenance strategies.

QuANTUM-First raises a new question: Who can avoid transplantation?

Experts say the significance of Vanflyta lies not simply in adding another FLT3 inhibitor to the treatment arsenal, but in its evaluation as part of a comprehensive strategy that includes maintenance therapy after induction and consolidation.

“Several FLT3 inhibitors—including midostaurin, quizartinib, gilteritinib, crenolanib, and sorafenib—have been studied over the years,” Professor Cheong said. “Quizartinib demonstrated promising clinical results, and notably, the QuANTUM-First trial focused exclusively on FLT3-ITD patients, allowing for a clearer evaluation in a more defined patient population.”

Professor Tsai agreed.

“Previous studies often failed to sufficiently focus on FLT3-mutated patients or did not clearly evaluate maintenance therapy,” he said. “The biggest differentiator for quizartinib is that it was used not only during induction and consolidation therapy, but also throughout maintenance treatment.”

In the QuANTUM-First study, the quizartinib combination arm demonstrated improved survival compared with placebo. Median overall survival was 31.9 months in the quizartinib arm vs. 15.1 months in the placebo arm. Median duration of complete remission was 38.6 months vs. 12.4 months, respectively, while the 12-month cumulative relapse rate was lower in the quizartinib group at 19 percent compared with 35 percent in the placebo group.

These findings renewed attention on the role of maintenance therapy in FLT3-ITD AML.

“After reviewing the quizartinib data, I became more confident in treating patients with maintenance therapy,” Professor Tsai said. “I am also satisfied with its feasibility for long-term use.”

In Taiwan, the introduction of Vanflyta has even prompted clinicians to reconsider transplant strategies in selected patients.

“For patients with NPM1 mutations who achieve MRD negativity, younger patients without suitable donors, or those unlikely to derive substantial benefit from transplantation, quizartinib maintenance may be considered,” Professor Tsai explained.

Professor Cheong acknowledged the same possibility.

“Every hematologic oncologist knows that stem cell transplantation has historically produced the best outcomes,” he said. “But transplantation involves introducing another person’s hematopoietic system into the patient. If comparable outcomes can be achieved without transplantation, avoiding it would naturally be preferable.”

At the same time, Cheonge urged caution.

“If quizartinib maintenance eventually demonstrates outcomes comparable to transplantation, many physicians would likely consider choosing it instead of transplant,” he said. “However, current evidence is still insufficient to make definitive conclusions.”

For now, Vanflyta cannot be considered a replacement for HSCT. Nevertheless, experts agree that it has introduced an important new question into FLT3-ITD AML management: not whether all patients require transplantation, but which patients truly need it and, which may achieve durable remission through maintenance therapy.

MRD assessment emerges as the key challenge

To discuss the possibility of omitting transplantation through quizartinib maintenance therapy, clinicians first need reliable ways to identify patients at lower risk of relapse. Both experts repeatedly emphasized the importance of "MRD evaluation."

“In patients with NPM1 mutations, NPM1 itself can serve as a good MRD marker,” Professor Tsai said. “If MRD negativity is confirmed in peripheral blood, the additional benefit gained from transplantation may be limited.”

The challenge, however, is that MRD assessment is not straightforward in all FLT3-ITD AML patients.

“For patients who have FLT3-ITD mutations without accompanying NPM1 mutations, highly sensitive FLT3-ITD MRD testing becomes necessary,” Tsai said. “Ultimately, the key issue is test accessibility and turnaround time.”

Delayed test results can directly delay treatment decisions.

“In highly sensitive FLT3-ITD MRD assays, obtaining results may take up to four weeks,” Professor Tsai explained. “By the time the sample is processed and the patient returns for follow-up, the patient’s condition may already have deteriorated. Even if a marker is useful in research settings, it can be difficult to apply in real-world clinical practice if results are not available in time.”

Korea faces similar challenges. Professor Cheong noted that standard FLT3 testing in Korea is typically performed at individual institutions and reported within about one week, but these are not highly sensitive MRD-level assays.

“When next-generation sequencing-based testing is performed, it usually takes about two weeks,” he said. “If combination strategies involving targeted therapy from the very beginning are to become standard practice, rapid confirmation of the patient’s genetic profile before starting chemotherapy is essential.”

Ultimately, experts said, the paradigm shift in FLT3-ITD AML treatment cannot be achieved through new drugs alone. Even with targeted therapies such as Vanflyta, clinicians need timely diagnostic systems that can determine which patients should receive which therapies and when.

Access, major challenge in Korea due to the reimbursement barrier

Professor Cheong June-won (KBR photo)

With the introduction of Vanflyta, treatment options for FLT3-ITD AML have expanded in Korea as well. Professor Cheong identified the ability to continue into maintenance therapy as one of the drug’s key strengths.

“If a patient is considered unlikely to undergo stem cell transplantation, clinicians may choose quizartinib from the initial treatment stage and continue treatment through maintenance therapy,” he said.

Conversely, treatment strategies may differ for patients who are expected to proceed to transplantation.

“In patients for whom transplantation is clearly necessary, clinicians may focus on completing treatment around the transplant itself rather than extending maintenance therapy for a prolonged period,” Cheong explained. “In such cases, options like midostaurin may still be considered.”

The major issue, however, is accessibility.

Although Korea’s overall treatment flow for FLT3-mutated AML is similar to Taiwan’s, actual drug access remains limited by cost. Even midostaurin—introduced earlier—has not yet been reimbursed in Korea, leaving patients with out-of-pocket costs of about 10 million won ($6,635).

“Despite this, many physicians still recommend midostaurin after thoroughly discussing its benefits with FLT3-mutated AML patients,” Professor Cheong said.

The reason is straightforward: unlike prolonged maintenance therapies, midostaurin is generally added only during induction and consolidation treatment for roughly two to three months.

“Even short-term use is considered clinically meaningful,” he said.

Still, not all patients can afford the expense.

“About 10 percent of patients ultimately forgo treatment because of the financial burden,” Professor Cheong noted.

Given this reality, experts say the key issue for Vanflyta in Korea will also be how quickly reimbursement barriers can be resolved after approval.

Acute leukemia is a disease that requires a rapid decision on treatment immediately following diagnosis. Patients and their families often do not have much time to deliberate on treatment costs. Even if treatment options exist, if they are not covered by insurance, those options inevitably become available only to a select few patients. Ultimately, the barrier posed by the lack of insurance coverage for FLT3 inhibitors in Korea is not merely a cost issue, but a matter of access that can determine patients’ initial treatment strategies and long-term prognosis.

Taiwan accelerates access through parallel approval, reimbursement, as well as separate funding

Professor Xavier Cheng-Hong Tsai (KBR photo)

Taiwan presents a somewhat different picture. According to Professor Tsai, midostaurin is reimbursed in Taiwan for up to six cycles, including induction, re-induction, and consolidation therapy. Vanflyta also entered reimbursement coverage relatively quickly following approval.

Tsai attributed Taiwan’s rapid adoption of Vanflyta partly to accumulated clinical experience. Taiwan participated in the QuANTUM-First trial and had previously used quizartinib through compassionate-use programs for relapsed patients.

“Even before formal approval, clinicians had already gained real-world experience with the drug and were familiar with its clinical effects,” he said.

Policy changes also played an important role.

“In the past, pharmaceutical companies had to obtain regulatory approval first and apply for reimbursement afterward,” Professor Tsai explained. “But the system changed, allowing approval and reimbursement applications to proceed simultaneously.”

He added that if a drug demonstrates sufficient efficacy and acceptable financial feasibility, the approval and reimbursement processes can now move in parallel.

“That policy change was likely one reason Vanflyta became available within roughly four months,” he said.

Separate funding mechanisms for innovative oncology drugs also contributed.

“With new anticancer agents and gene therapies continuously emerging, delays are inevitable if every product competes within the same budget,” Professor Tsai said. “Taiwan established an independent funding system for new oncology drugs, and this may have facilitated the rapid adoption of some novel therapies.”

The case of Taiwan demonstrates that the rapid adoption of Vanflyta was not driven solely by the drug’s efficacy. Rather, it resulted from the combined effects of clinical experience, a system allowing for concurrent approval and reimbursement, and separate financial support for new anticancer drugs. This suggests that reimbursement and financial systems—which connect new drugs to actual patients—are just as important as the drugs’ medical value.

Targeted therapy expands options, but transplantation still matters

Although Vanflyta has broadened treatment options for FLT3-ITD AML, both experts agreed that the role of stem cell transplantation is unlikely to disappear anytime soon.

“Low-risk patients may achieve outcomes with chemotherapy alone that are comparable to those seen with transplantation,” Professor Cheong said. “With the addition of newer drugs, some intermediate-risk patients may also achieve transplant-like outcomes without undergoing transplantation.”

Still, he stressed that this possibility applies only to selected patient groups.

“Progress in AML has historically been slower than in many other diseases, but gradual improvements are being made,” he said. “Going forward, treatment strategies will likely become more individualized even within the intermediate-risk category.”

Professor Tsai emphasized the biological complexity of leukemia itself.

“Some patients initially present with a single leukemia clone, but at relapse they may develop five, six, or even more distinct clones,” he explained. “If only one targeted therapy is used, certain clones may be suppressed while others emerge as dominant clones and drive relapse.”

“One way to suppress multiple clones simultaneously is stem cell transplantation,” Tsai added. “However, transplantation also carries substantial treatment-related mortality and morbidity. If effective early therapies can adequately suppress potential clones from the outset, the burden of later treatment may be reduced.”

Professor Cheong echoed this view.

“The ideal strategy is to complete treatment before leukemia clones acquire mechanisms of treatment resistance,” he said.

'The greatest significance is giving patients better options'

Experts agreed that the significance of Vanflyta does not lie in replacing transplantation outright. Rather, it lies in adding maintenance therapy to the existing treatment pathway and enabling more refined, risk-adapted strategies tailored to individual patients.

“When FLT3-ITD mutations are identified, clinicians can now apply targeted therapies aimed at maintaining remission, which will likely increase motivation for testing,” Professor Tsai said. “In the future, some patients may choose maintenance therapy over transplantation.”

Still, he emphasized that broader adoption of maintenance strategies will require continued confidence in long-term safety and more precise MRD monitoring.

Professor Cheong similarly stressed the value of expanding treatment options.

“To provide patients with even slightly better outcomes, clinicians must consider every possible therapeutic option,” he said. “The greatest significance of new drugs is that they broaden the range of choices available to patients.”

He added that the emergence of quizartinib is especially meaningful for patients who can tolerate chemotherapy but are unable to proceed to transplantation.

“If FLT3 mutations are identified in such patients, clinicians now have the option of combining quizartinib during initial treatment and continuing into maintenance therapy afterward,” he explained.

Ultimately, experts said, Vanflyta’s significance lies not in replacing transplantation but in enabling more individualized treatment intensity based on MRD status and patient-specific risk. It also offers a maintenance option for patients unable to undergo a transplant.

The next challenge in AML treatment is no longer simply intensifying therapy for everyone, but accurately identifying each patient’s risk profile quickly enough to select the most appropriate treatment. The arrival of Vanflyta signals that FLT3-ITD AML care is moving beyond a uniform transplant-centered pathway toward a precision medicine era shaped by MRD assessment, maintenance therapy, and treatment accessibility.

Kim Yun-mi