The argument builds on a striking real-world study that has recently energized the field. A retrospective, two-stage cohort analysis by Chen and colleagues examined early bone-marrow-guided venetoclax management in patients with newly diagnosed acute myeloid leukemia who were considered unsuitable for intensive chemotherapy. Among 371 evaluable patients, the investigators found that using early marrow assessments to guide treatment was associated with significantly reduced early venetoclax exposure and a marked drop in day-56 infection-related hospitalization, which fell from 37.4 percent to 24.0 percent, corresponding to an adjusted odds ratio of 0.46 with a p-value of 0.005. In other words, simply looking at the marrow earlier allowed clinicians to pull back on the drug before the most dangerous toxicities took hold.

The second stage of the Chen study sharpened the finding further. Among 237 patients who responded to initial therapy, shortening venetoclax to fourteen days or fewer per cycle reduced prolonged grade-4 neutropenia from 61.0 percent to 41.6 percent, an adjusted odds ratio of 0.41 with a p-value of 0.003. Infection-related hospitalization also fell, with an adjusted odds ratio of 0.43 and a p-value of 0.014. Critically, these toxicity reductions came without any significant change in measurable residual disease negativity, overall survival, or relapse-free survival. For a drug whose most feared side effect is profound, prolonged neutropenia that opens the door to life-threatening infections, the implication is provocative: some patients may be receiving more venetoclax than they need, and the excess exposure may be pure harm.

Yet the editorial is careful to frame these results as a beginning rather than an endpoint. Because the Chen study was retrospective, its findings are vulnerable to selection bias; clinicians may have shortened therapy preferentially in patients who already looked healthier, which could inflate the apparent safety benefit. The absence of randomization means the two compared groups may have differed in ways the statistical adjustments could not fully capture. Adnan also notes that the study showed no significant difference in overall survival or progression-free survival, which supports the idea that shortening was not harmful but does not prove that shortened venetoclax is truly equivalent in efficacy. Prospective, ideally randomized validation remains the essential next step before practice changes on a wide scale.

There is a deeper conceptual problem as well, and it sits at the heart of the proposed framework. Bone marrow morphology, the century-old practice of examining stained marrow smears under a microscope, is functional and widely available, but it is a blunt instrument. It can miss small populations of leukemic cells that persist below the threshold of visual detection, and its interpretation varies between observers. The editorial contends that early marrow morphology is useful but insufficient on its own, and that relying on a single marker to decide whether to curtail a backbone therapy in a disease as heterogeneous as acute myeloid leukemia is inherently risky.

This is where measurable residual disease enters the picture. A consensus document from the European LeukemiaNet MRD Working Party, authored by Heuser and colleagues, established MRD as a central biomarker in acute myeloid leukemia, serving prognostic, predictive, monitoring, and efficacy-response functions. A positive or negative MRD result indicates whether quantifiable disease is detected above specific thresholds, but those thresholds differ depending on the assay and the laboratory performing it. Flow cytometry, polymerase chain reaction-based assays for mutations such as NPM1, and other techniques each carry distinct sensitivities and limitations, which means an MRD result must always be interpreted in context rather than treated as an absolute verdict.

Recognizing these limitations, recent work by Bancos and colleagues has advocated a multimodal approach to residual disease assessment, tracing the evolution from cytogenetics and molecular biology to emerging technologies such as methylation pattern analysis and surface-enhanced Raman scattering. Each molecular marker, whether marrow morphology, conventional MRD, or molecular MRD via next-generation sequencing, may contribute to diagnosis and monitoring, but none is individually sufficient to guide every treatment decision. The editorial takes this logic one step further and applies it specifically to the question of venetoclax duration, proposing that the integration of multiple markers could provide a more precise and personalized basis for deciding when to stop or shorten therapy.

The framework also draws inspiration from the broader multi-omics movement in hematology. A review by Soleimani Samarkhazan highlighted how integrating complementary molecular and transcriptomic indicators can enable more accurate response-adapted approaches in acute myeloid leukemia, potentially allowing venetoclax duration to be customized according to both morphological and biological measures of disease response. Under such a model, a patient whose marrow clears rapidly, whose MRD assays turn negative early, whose leukemic clone shows molecular responses on sequencing, and whose blood counts recover promptly might safely de-escalate to shorter venetoclax cycles. Conversely, a patient with persistent molecular evidence of disease might continue full-dose therapy or be considered for escalation, even if the microscope looks reassuringly empty.

The stakes of getting this right are considerable. Acute myeloid leukemia is a progressively increasing form of leukemia with consistently high incidence and mortality, imposing a growing strain on health systems worldwide. Projections based on the Global Burden of Disease Study 2021 estimate that by 2040 the number of cases will rise significantly, with predicted figures reaching approximately 184,287.88 for incidence and 165,537.59 for mortality. The economic toll is equally sobering: a United States analysis by Hagiwara and colleagues of 9,455 newly diagnosed patients found that the average healthcare cost per patient was 386,077 dollars. Every day of unnecessary venetoclax exposure adds hospitalizations, growth factor use, transfusions, and infection management to that bill, while every day of insufficient exposure risks relapse, which is far more expensive and far more deadly.

What makes the editorial’s proposal compelling is that it reframes a question the field has been circling for years. Venetoclax-based regimens have delivered unprecedented response rates in unfit patients, but the drug’s hallmark toxicity, myelosuppression, has remained a stubborn constraint, and clinicians have lacked a principled way to know when enough is enough. By proposing a multi-marker panel that unites marrow morphology, MRD, molecular MRD via next-generation sequencing, and hematologic recovery, the editorial sketches a route toward treating venetoclax duration the way modern oncology treats nearly everything else: as a variable to be tuned by data rather than fixed by tradition. The author acknowledges the constraints of the underlying evidence, including the retrospective design of the pivotal real-world study and the possibility that no single marker can capture the full complexity of the disease. But the direction of travel is clear, and the call for prospective research into a multi-marker response-adapted framework gives the field a concrete hypothesis to test. If randomized studies confirm that response-guided shortening preserves survival while stripping away toxicity, the fixed ten-plus-month venetoclax paradigm could give way to something smarter, safer, and genuinely personal, and the editorial argues that the tools to build that future are already on the laboratory bench.

Subject of Research: Response-adapted venetoclax dosing guided by multi-marker disease assessment in acute myeloid leukemia

Article Title: Presenting a multi-marker response-adapted framework for venetoclax duration in acute myeloid leukemia

Article References: Adnan, N. (2026). Presenting a multi-marker response-adapted framework for venetoclax duration in acute myeloid leukemia. Annals of Hematology, 105(10), Article 414. https://doi.org/10.1007/s00277-026-07280-x

Image Credits: AI Generated

DOI: 10.1007/s00277-026-07280-x

Keywords: acute myeloid leukemia, venetoclax, measurable residual disease, bone marrow morphology, next-generation sequencing, BCL-2 inhibitor, neutropenia, response-adapted therapy, multi-omics, hematology, treatment de-escalation, European LeukemiaNet