Impact of prolonged dose delays on response with belantamab mafodotin (belamaf; gsk2857916) treatment in dreamm-2 study: 13-month follow-up
Bibliographic record
Abstract
Introduction: Single-agent belamaf (BLENREP) demonstrated deep and durable responses in the DREAMM-2 (NCT03525678) primary analysis(1) and long-term follow-up.(2,3) Keratopathy (microcyst-like epithelial changes [MECs] observed on eye examination with/without symptoms) were managed through dose delays and reductions. The aim of this study is to provide an update on the impact of dose delays on responses in patients receiving single-agent belamaf 2.5-mg/kg in DREAMM-2 (13-month follow-up). Methods: In the DREAMM-2 study (single-agent belamaf 2.5 mg/kg [n=97] or 3.4 mg/kg [n=99] Q3W), dose modifications were permitted to manage adverse events (AEs), including keratopathy (MECs), an eye examination finding that may/may not be associated with symptoms. Objective response (International Myeloma Working Group criteria 2016) was assessed by an independent review committee Q3W, regardless of treatment delays. Here, we report a post-hoc analysis on the impact of dose delays >63 days on clinical response in the 2.5-mg/kg arm (the selected dose for future clinical development based on risk–benefit assessment). Results: In patients receiving single-agent belamaf (2.5 mg/kg), dose delays (54%) and reductions (35%) due to AEs were common.(2,3) Keratopathy (MECs) was the most frequent reason for dose delays (47%) and reductions (25%), leading to only 1 patient (1%) discontinuing treatment.(2,3) Of 31 patients with ≥partial response (PR), 16 had prolonged treatment interruptions (>63 days). Of these 16 patients, 14 (88%) continued experiencing a clinical benefit during the first prolonged delay: 6 (38%) deepened their response during delay (1 stable disease to minimal response [MR]; 2 PR to very good partial response [VGPR]; 2 MR to VGPR; 1 VGPR to confirmed response); 6 (38%) maintained the same response category as of the last evaluable assessment during delay/first evaluable assessment after delay; 2 (13%) had increasing paraproteins during the delay but did not meet progression criteria. Two (13%) developed disease progression (1 patient 6 weeks into delay; 1 patient 3 weeks after delay). Conclusions: Despite dose delays lasting for several cycles to manage AEs, most responses were sustained throughout the delay, thus maintaining clinical benefit for the majority of patients. Funding: GSK (205678). Drug linker technology licensed from Seattle Genetics; monoclonal antibody produced using POTELLIGENT Technology licensed from BioWa. Encore Statement: ©2020 Society of Hematologic Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2020 SOHO Annual Meeting. All rights reserved. 1. Lonial Lancet Oncol 2020; 2. Lonial ASCO 2020, EP436; 3. Lonial EHA 2020. EP970.
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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 | 0.008 | 0.005 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.003 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".