Mosunetuzumab Monotherapy Continues to Demonstrate Durable Responses in Patients with Relapsed and/or Refractory Follicular Lymphoma after ≥2 Prior Therapies: 3-Year Follow-up from a Pivotal Phase II Study
Notice bibliographique
Résumé
Background: Mosunetuzumab is a CD20xCD3 T-cell engaging bispecific antibody that redirects T cells to eliminate malignant B cells. In a pivotal Phase II study (NCT02500407), mosunetuzumab demonstrated a high complete response (CR) rate with a manageable safety profile in patients with relapsed/refractory (R/R) follicular lymphoma (FL) and ≥2 prior lines of therapy (Budde et al. Lancet Oncol 2022). Mosunetuzumab is a fixed-duration treatment that can be administered in an outpatient setting. Here, we present updated data for patients with R/R FL and ≥2 prior lines of therapy, after 3 years of follow-up. Methods: Eligible patients with R/R FL Grade (Gr) 1-3a and ≥2 prior therapies received intravenous mosunetuzumab in 21-day cycles with step-up dosing in Cycle (C) 1 (C1 Day [D] 1, 1mg; C1D8, 2mg; C1D15/C2D1, 60mg; C3D1 and onwards, 30mg). Hospitalization for treatment was not required. Patients achieving a CR by C8 completed treatment without additional cycles; patients with a partial response or stable disease received a total of 17 cycles. The primary endpoint was CR rate as determined by an Independent Review Committee (as best response; Cheson 2007 criteria). Duration of response (DOR), duration of complete response (DOCR), progression-free survival (PFS), event-free survival (EFS), and safety were secondary endpoints. Time to next treatment (TTNT), response to retreatment, biomarkers of minimal residual disease (MRD), and circulating B-cell counts were exploratory endpoints. Results: Ninety patients with R/R FL were enrolled. As of May 2, 2023, median time on study was 37.4 (range: 2.0-48.0) months. Investigator-assessed best overall response and CR rates were 77.8% (95% CI: 67.8-85.9) and 60.0% (95% CI: 49.1-70.2), respectively. The median DOR was 35.9 months (95% CI: 20.7-not reached [NR]). Median DOCR was NR (95% CI: 33.0-NR); the estimated 30-month DOCR rate was 72.4% (95% CI: 59.2-85.6) ( Table). Three years after the end of treatment, 57.1% of 70 responding patients were alive and disease progression-free. Median PFS was 24.0 months (95% CI: 12.0-NR) ( Figure). The median TTNT was 37.3 months (95% CI: 18.0-NR); estimated EFS at 36 months was 51.8% (95% CI: 40.8-62.8). After initial mosunetuzumab treatment, 34/90 (37.8%) patients had received a new anti-lymphoma therapy, including 33/90 (36.7%) patients who received a new systemic treatment (8/33 [24.2%] of these patients received chimeric antigen receptor T-cell therapy); 8/90 (8.9%) had radiotherapy; 2/90 (2.2%) had excision of tumor; 2/90 (2.2%) had an allogeneic stem cell transplant; and 1/90 (1.1%) had an autologous stem cell transplant. Five patients received retreatment with mosunetuzumab, 3/5 of these patients had a CR. No new cytokine release syndrome (CRS) events, serious, or Gr ≥3 adverse events (AEs) were reported since the previous analysis (median follow-up of 28.3 months; Bartlett et al. ASH 2022). CRS events occurred in 44.4% of patients and 2.2% were Gr 3/4 in severity; all CRS events resolved. Overall AEs and serious AEs were comparable to the previous analysis (Bartlett et al. ASH 2022); febrile neutropenia was not reported. Forty-six (51.1%) patients experienced Gr 3/4 AEs related to mosunetuzumab; the rate of AEs leading to discontinuation was low (4.4%). Peripheral blood B-cell depletion following treatment with mosunetuzumab occurred in all patients, and recovery was observed after a median of 18 months following the end of treatment in patients with a sustained response using follow-up samples. MRD kinetics following mosunetuzumab therapy will be presented. Conclusions: In this updated analysis, with a median follow-up of 37.4 months, durable responses continued to be observed with fixed-duration mosunetuzumab in patients with R/R FL. The manageable safety profile was consistent with previous reports. Evidence of B-cell recovery was observed after a median of 18 months following the end of treatment.
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
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