PF614 PATIENT‐REPORTED OUTCOMES FROM THE INNOVATE™ STUDY: RESULTS OF IBRUTINIB‐RITUXIMAB IN WALDENSTRÖM MACROGLOBULINEMIA (WM)
Bibliographic record
Abstract
Background: Anemia and fatigue can impair quality of life in patients (pts) with WM and are common reasons for the initiation of WM treatment. Ibrutinib, a first‐in‐class, once‐daily inhibitor of BTK, is approved in the EU for the treatment of WM after ≥1 prior therapy or as first‐line therapy in pts unsuitable for chemoimmunotherapy. In the US, ibrutinib is approved for the treatment of WM as single agent or in combination with rituximab. Single‐agent ibrutinib has been shown to induce clinically meaningful improvements in pt‐reported outcomes (PROs) in pts with rituximab‐refractory WM (Trotman, EHA 2017). In the primary analysis of the phase 3 iNNOVATE study, ibrutinib‐rituximab produced higher rates of sustained hemoglobin improvement and meaningful improvements in PROs when compared with placebo‐rituximab (Dimopoulos NEJM 2018). Here, we report a more detailed analysis of PROs from iNNOVATE. Aims: To evaluate data on PROs from the iNNOVATE study to assess pts’ perspectives of the therapeutic benefit of ibrutinib‐rituximab. Methods: Pts with symptomatic WM requiring therapy were randomized to daily 420 mg oral ibrutinib or placebo until progressive disease or unacceptable toxicity. Both arms also received rituximab (375 mg/m 2 /week IV at weeks 1–4 and 17–20). PRO measures evaluated in this analysis included FACIT‐Fatigue (FACIT‐F), FACT‐An total score (TS) and anemia subscale score (AS), and EQ‐5D‐5L (© EuroQol Research Foundation. EQ‐5D™ is a trade mark of the EuroQol Research Foundation) visual analog scale (VAS) and utility score (US). Results: For the 150 randomized pts (75/arm), the most common reasons for initiating treatment were fatigue (61%), constitutional symptoms (32%), and anemia (32%). Baseline PRO scores were comparable in both arms. Overall (median follow‐up, 26.5 months), more pts showed clinically meaningful improvement in FACIT‐F, TS, and AS with ibrutinib‐rituximab than placebo‐rituximab (Table & Figure). The median time to PRO improvement was short (1–2 months) and comparable in both arms. A correlation analysis conducted at week 25 showed that changes in hemoglobin levels correlated with FACIT‐F (Pearson coefficient r = 0.28), TS (r = 0.29), and AS (r = 0.26) in the ibrutinib‐rituximab arm; no meaningful correlations were observed on placebo‐rituximab. Changes in IgM levels correlated with FACIT‐F (r = −0.32), TS (r = −0.33), AS (r = −0.35), and EQ‐VAS (r = −0.26) for ibrutinib‐rituximab and with FACIT‐F (r = 0.29) and TS (r = 0.35) for placebo‐rituximab. Summary/Conclusion: These results show that in pts with WM, clinical response and improvements in anemia with ibrutinib‐rituximab are consistent with more pts showing clinically meaningful improvement in PROs compared with placebo‐rituximab. Changes in IgM correlate with improvements in PROs in pts treated with ibrutinib‐rituximab. image
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 teacher head, 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".