PF411 ENESTOP 192‐WK RESULTS: DURABILITY AND IMPACT ON QUALITY OF LIFE OF TREATMENT‐FREE REMISSION (TFR) FOLLOWING SECOND‐LINE (2L) NILOTINIB (NIL) IN PATIENTS (PTS) WITH CHRONIC MYELOID LEUKEMIA (CML)
Bibliographic record
Abstract
Background: The ENESTop study (NCT01698905) is evaluating TFR in pts with CML in chronic phase who achieved sustained deep molecular response with 2L NIL. In the primary analysis, 57.9% of pts remained in TFR 48 wks after stopping NIL. Analyses at 144 wks showed durability of TFR. Aims: To assess the maintenance and safety of TFR after a longer follow‐up of 192 wks. Methods: Eligible pts had received ≥3 y of treatment (including >4 wks of imatinib followed by ≥2 y of NIL) and had achieved MR4.5 (BCR‐ABL1 IS ≤0.0032%) on NIL. Pts without confirmed loss of MR4.5 after 1 y of consolidation (CONS) treatment could attempt TFR. NIL was resumed upon loss of major molecular response (BCR‐ABL1 IS ≤0.1%) or confirmed loss of MR4 (BCR‐ABL1 IS ≤0.01%). By the data cut‐off (24 Sep 2018), all pts had either completed ≥192 wks of TFR, resumed NIL, or discontinued the study. Results: At the data cut‐off, of the 126 pts who entered TFR, 56 remained in TFR, 59 had resumed NIL and 11 had discontinued the study. At 192 wks, the TFR rate was 46.0% (58/126; 95% CI, 37.1–55.1%); all but 1 pt were in MR4.5. Of pts in TFR at 144 wks, only 1/61 had lost response (confirmed loss of MR4) by 192 wks; 2 other pts had discontinued due to pt/guardian decision and serious AE (polycythemia vera), respectively. Of pts who resumed NIL, 56/59 (94.9%) and 55/59 (93.2%) regained MR4 and MR4.5, respectively. Of 56 pts who regained MR4, 40 (71.4%) had stable MR4 96 wks later; the remaining 16 had either discontinued <96 wks after regaining MR4 (n = 12) or were ongoing with <96 wks after regaining MR4 (n = 4). Of 55 pts who regained MR4.5, 37 (67.3%) had stable MR4.5 96 wks later; the remaining 18 pts had either discontinued <96 wks after regaining MR4.5 (n = 12) or were ongoing with <96 wks after regaining MR4.5 (n = 6). There were no cases of disease progression or deaths due to CML. No new deaths have occurred since the 144‐wk analysis. The treatment‐free survival rate at 192 wks was 50.3% (95% CI, 41.2–58.7%; Figure). During CONS and the 1st, 2nd, 3rd and 4th 48‐wk periods of TFR, respectively, rates of all‐grade AEs were 80.6%, 85.5%, 67.7%, 51.6% and 56.5% among the 62 pts who remained in TFR for >144 wks. Musculoskeletal pain AE rates increased during the first 48 wks of TFR (53.2%) vs CONS (11.3%), then decreased during each subsequent 48‐wk period of TFR to levels below that seen in CONS (21.0%, 14.5% and 3.2%, respectively). In pts who resumed NIL (n = 59), the most common AEs were hypertension (20.3%) and arthralgia (13.6%), with the majority of AEs being grade 1/2. The rates of frequently occurring (>10% on treatment) additional AEs (grouped by category) that may affect quality of life were assessed during CONS and the subsequent 48‐wk periods of TFR to further explore the potential impact of TFR. During these study periods, respectively, incidences of these categories of AEs were: gastrointestinal disorders, 22.6%, 17.7%, 21.0%, 8.1% and 8.1%; infections and infestations, 35.5%, 37.1%, 21.0%, 17.7% and 16.1%; musculoskeletal and connective tissue disorders: 24.2%, 62.9%, 29.0%, 22.6% and 12.9%; general disorders and administration site conditions (eg, asthenia, pyrexia): 11.3%, 21.0%, 4.8%, 4.8% and 6.5%. Across these AE categories, incidences tended to decrease over time in TFR. Summary/Conclusion: These results demonstrate the long‐term durability and safety of TFR following 2L NIL. No disease progressions or CML‐related deaths were reported. Musculoskeletal pain AEs were transient and additional AEs that may impact quality of life tended to decrease in frequency during TFR. image
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".