Patients with Philadelphia-positive B-cell acute lymphoblastic leukemia (Ph-positive B-ALL) treated with blinatumomab plus ponatinib in the first- or second-line setting who discontinue maintenance TKI monotherapy after remission show favorable outcomes, new research shows.
As of the final blinatumomab cycle, minimal residual disease negativity was achieved in 64.5% of patients, and median overall survival (OS) and event-free survival (EFS) rates were not reached.
Among the patients, "ponatinib discontinuation appeared to be feasible after a median of 31 months from the start of blinatumomab," said first author Abigail Huetteman, MD, of the H. Lee Moffitt Cancer Center, in Tampa, Florida, while presenting the findings at the Society of Hematologic Oncology (SOHO) 2026 meeting. "Our interpretation is not that TKI therapy should be routinely discontinued in all patients." However, "the data supports that in the selected group of patients treated in the frontline or second-line setting who have achieved a sustained, complete molecular response, discontinuation of ponatinib may be a feasible strategy with close molecular monitoring."
While Ph-positive B-ALL was once associated with poor prognoses, the advent of TKI therapy substantially improved outcomes for patients, and the recent combination of the TKI ponatinib with blinatumomab has gained favor as a key chemotherapy-free approach for patients.
Guidelines recommend that patients continue on TKI maintenance therapy following remission, however, data is lacking regarding the optimal duration of the maintenance therapy, and safety of discontinuation, Huetteman explained.
The authors of the new retrospective study sought to answer: Once a patient has achieved a sustained and deep molecular response, how long do they need to continue TKI therapy?
The study included 31 adult patients with Ph-positive B-ALL treated with blinatumomab plus ponatinib at the Moffitt Cancer Center between January 2017 and October 2025 and who had discontinued their TKI therapy. Of the patients, 16 had relapsed/refractory disease, 15 had prior TKI exposure, and eight (25.8%) had higher-risk IKZF1 mutations.
"Overall, this was a heterogeneous group that included both patients treated in the frontline setting as well as a substantial number of patients who had more advanced disease," Huetteman noted.
The median number of blinatumomab cycles was three (range, 1-9), with a median follow-up of 54.2 months (range, 19.9-119.8 months), and the median treatment duration with ponatinib was 30.3 months (range, 0.9-60 months).
Notable differences were observed with greater previous lines of treatment. OS rates from the date of diagnosis in the firstline and second-line groups were 100% at 60 months, compared with 75% in the third-line setting, and similar results were observed in OS rates from the date of TKI discontinuation (P = .017).
Following discontinuation of ponatinib, the 24-month EFS in the entire cohort was 79.5%, with a rate of 77.9% in the minimal residual disease (MRD)-negative cohort, and 66.7% in the MRD-positive cohort (P = .24).
Patients receiving first- or second-line therapy also showed superior 60-month EFS following TKI discontinuation, with an OS of 100% and only one relapse. The median EFS was not reached vs 26.9 months in the first/second-line vs third-line therapy groups, with 24-month EFS of 90.9% vs 55.6%, respectively (P = .011).
The lower survival rates in the third-line treatment group were largely due to complications relating to the patients' underlying higher-risk status as opposed to relapse, Huetteman explained. In those higher-risk patients, among three patients with purposeful discontinuations that were related to complete molecular responses, all three continued to be in sustained complete molecular response.
"I think the important message from this is not simply that these two groups [first-and second-line vs third-line] have different overall survival, but rather the third-line setting represents a fundamentally different and high-risk clinical population in whom we observed the events to be related to toxicity rather than to relapse," she explained.
While the study showed feasibility of TKI discontinuation in a small number of those patients, "the risks and benefits for each patient in this group need to be carefully weighed," Huetteman added. However, the ideal use of clinical as well as molecular risk factors can allow for more personalized treatment of all patients.
"At Moffitt, we use clonoSEQ along with BCR-ABL1 about every 3 months as a part of this monitoring strategy, with the goal of identifying an emerging molecular signal before an overt hematologic relapse," she said. "Ultimately, the goal would be to move towards a more individualized approach to TKI duration rather than an indefinite maintenance therapy for everyone."
Commenting on the research, Selina Luger, MD, of the Abramson Cancer Center, Perelman Center for Advanced Medicine, Philadelphia, who co-moderated the session, characterized the study as "very encouraging."
"It suggests that patients who discontinue TKIs once in a durable complete molecular remission could be at no or minimal risk of death due to failure or disease relapse secondary to discontinuation," Luger told Medscape Medical News. "This is a very important observation and encourages us to perform a larger study."
Huetteman did not report any disclosures. Luger reported consulting for Amgen, AstraZeneca, Daiichi Sankyo, and Geron.
Facts Only
* Patients with Ph-positive B-ALL treated with blinatumomab plus ponatinib who discontinue maintenance TKI monotherapy after remission showed favorable outcomes.
* Minimal residual disease negativity was achieved in 64.5% of patients at the final blinatumomab cycle.
* Median overall survival (OS) and event-free survival (EFS) rates were not reached.
* Discontinuation of ponatinib appeared feasible after a median of 31 months from the start of blinatumomab in the selected group.
* The study included 31 adult patients with Ph-positive B-ALL treated with blinatumomab plus ponatinib at Moffitt Cancer Center between January 2017 and October 2025.
* Eight patients (25.8%) had higher-risk IKZF1 mutations.
* Median treatment duration with ponatinib was 30.3 months.
* Overall survival rates from diagnosis in the first-line and second-line groups were 100% at 60 months, compared with 75% in the third-line setting.
* 24-month EFS following ponatinib discontinuation was 79.5% in the entire cohort, 77.9% in the MRD-negative cohort, and 66.7% in the MRD-positive cohort.
* Patients with purposeful discontinuations related to complete molecular responses in the third-line setting remained in sustained complete molecular response.
Executive Summary
Full Take
The framing suggests that the clinical decision around TKI discontinuation is not a uniform protocol but must be highly personalized based on disease setting and molecular response depth. The core tension lies between established guidelines advocating for continued maintenance therapy post-remission and emerging data suggesting feasibility of discontinuation for select, favorably responding patients, particularly those in earlier lines of treatment who have achieved deep molecular responses. The observation that survival differences correlate more strongly with the initial treatment line (first/second-line versus third-line) than with the act of stopping the TKI suggests that the context of prior risk—the inherent aggressiveness reflected by the disease stage and known mutations—is a more significant prognostic factor than the TKI continuation itself. This points to a systemic need to refine risk stratification models so that discontinuation decisions are not based on generalized timelines but on individualized molecular monitoring, as proposed by the follow-up strategy using clonoSEQ. The potential for toxicity versus relapse becomes a differential diagnostic issue heavily influenced by preceding clinical history.
Bridge Questions: How can real-world healthcare systems integrate dynamic molecular monitoring tools like clonoSEQ into standard maintenance protocols to facilitate these personalized discontinuation decisions? What specific, quantifiable thresholds of sustained molecular response justify TKI cessation in high-risk versus low-risk populations? If discontinuation is feasible for achieving molecular endpoints, what are the long-term safety implications when relying on post-cessation surveillance rather than indefinite TKI presence?