Preliminary results of a phase II randomized study (ROMULUS) of polatuzumab vedotin (PoV) or pinatuzumab vedotin (PiV) plus rituximab (RTX) in patients (Pts) with relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL).
Bibliographic record
Abstract
8519 Background: PoV and PiV, antibody drug conjugates (ADC) containing the anti-mitotic MMAE targeting CD79b (PoV) and CD22 (PiV), showed clinical activity in Phase I. The current study aims to compare PoV and PiV + RTX in R/R DLBCL and R/R follicular lymphoma (FL). Methods: Pts were randomized to receive PoV or PiV + RTX (ADC 2.4 mg/kg + RTX 375 mg/m2) every 21 days. Tumor assessments were performed every 3 months. Results: As of 8 November 2013, 58 received PoV + RTX (38 DLBCL; 20 FL), 63 PiV + RTX (42 DLBCL; 21 FL). Median prior therapies [DLBCL, 3 (1-10); FL, 2 (1-8)] were balanced between treatment arms; 46% were RTX refractory. Median treatment (tx) cycles in DLBCL: 5 for both ADC (1-15); FL: 8.5 PoV (3-15) and 6 PiV (1-13). Overall safety profiles of both regimens were similar. Tx-emergent adverse events (AE) >25%: fatigue (52%), diarrhea (42%), nausea (37%), peripheral neuropathy (PN) (32%), constipation (26%). Grade ≥ 3 AE >3%: neutropenia (21%), diarrhea (6%), dyspnea (4%), febrile neutropenia (4%), hyperglycemia (4%) and PN (4%). Serious AE reported in 36%. Thirty-eight discontinued tx for AE after median 5 doses (range 1-14), including 16 for PN. Tx delays and ADC dose reductions reported in 27% and 22%. Two of 7 deaths (sepsis, urosepsis) unrelated to NHL were attributed to PiV. Complete (CR) and partial (PR) responses, n (%) [% 95% CI] (see Table). Conclusions: PoV and PiV + RTX were generally well-tolerated with similar toxicity. Neutropenia, PN and diarrhea were principal toxicities. Similar efficacy was observed with both ADCs in heavily pretreated pts with DLBCL. The higher CR rate with PoV + RTX suggests greater clinical activity in R/R FL. Combination studies of R + PoV with chemotherapy and with ADC schedules to reduce PN are ongoing or in planning. Clinical trial information: NCT01691898. PoV (CD79b) + RTX PiV (CD22) + RTX R/R DLBCL ORR CR PR N = 37 19 (51%) [34, 68] 5 (14%) [5, 29] 14 (38%) [23, 55] N = 37 20 (54%) [37, 71] 7 (19%) [8, 35] 13 (35%) [20, 53] R/R FL ORR CR PR N = 20 12 (60%) [36, 81] 6 (30%) [12, 54] 6 (30%) [12, 54] N = 21 14 (67%) [43, 85] 1 (5%) [0.1, 24] 13 (62%) [38, 82] Pharmacokinetic profiles were similar for both ADCs across DLBCL and FL with no free MMAE accumulation.
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 | 0.003 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 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".