Mosunetuzumab Monotherapy Demonstrates Activity and a Manageable Safety Profile in Patients with Relapsed or Refractory Richter's Transformation
Notice bibliographique
Résumé
Background: Richter's transformation (RT) is characterized by the development of chronic lymphocytic leukemia to an aggressive lymphoma, most commonly CD20+ large B-cell lymphoma. RT remains an unmet medical need with a poor prognosis and no standard of care. Mosunetuzumab is a CD20xCD3 T-cell engaging bispecific antibody that redirects T cells to eliminate malignant B cells. In a Phase I/II study (NCT02500407), fixed-duration mosunetuzumab monotherapy demonstrated notable efficacy and a manageable safety profile in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (Bartlett et al. Blood Advances 2023). We report the efficacy and safety of mosunetuzumab monotherapy in patients with R/R RT after a median follow-up of 8.7 (range: 1-37) months. Methods: Eligible patients with R/R RT and ≥1 prior therapies were enrolled. Patients with lymphocyte counts of ≥5000/µL were excluded. Mosunetuzumab was administered intravenously 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 complete response (CR) by C8 completed treatment without additional cycles; patients with a partial response (PR) or stable disease received a total of 17 cycles. The primary endpoints were safety and tolerability. Efficacy was a secondary endpoint and was assessed according to Cheson 2007 criteria. Cytokine release syndrome (CRS) events were graded using the American Society for Transplantation and Cellular Therapy criteria (Lee et al. Biol Blood Marrow Transplant 2019). Results: Twenty patients with R/R RT were enrolled. Median age was 70 (range: 49-87) years, 95.0% of patients had Ann Arbor stage III/IV disease, and 70.0% had an International Prognostic Index score of ≥3. Median number of prior therapies was 2.5 (range: 1-10), 65.0% of patients had ≥2 prior therapies, and 45.0% had received prior treatment with a Bruton tyrosine kinase inhibitor. Overall, 80.0% of patients were refractory to their last therapy. Investigator-assessed overall response and CR rates were 40.0% and 20.0%, respectively. Of four patients with a CR, two had a CR ongoing for ≥20 months at data cut-off (duration of CR [DOCR] at data cut-off: 21.2 months [patient had disease progression at a later timepoint] and 34.2 months), and the other two patients had received a subsequent stem-cell transplant (DOCR with mosunetuzumab: 0.1 and 4.2 months) ( Figure). The four patients with a PR had individual durations of response of: 1.7, 2.1, 2.3, and 2.8 months. The most common adverse event (AE) was CRS (65.0%), and events were predominantly Grade (Gr) 1 (20.0%) or Gr 2 (40.0%); a Gr 3 event was reported after C1D15 in one patient (5.0%). CRS was primarily associated with treatment administration during C1 (C1D1, 15.0%; C1D15, 50.0%); a Gr 1 CRS event was reported in one patient (5.0%) during C2. Of the 14 patients with CRS, six (42.9%) received tocilizumab, three (21.4%) received low-flow oxygen, one (7.1%) received a single pressor, and four (28.6%) received steroids; of the patients who received steroids, two (14.3%) received both tocilizumab and steroids. One patient was admitted to the intensive care unit for the management of Gr 3 CRS. The median duration of CRS was 3 (range: 1‒9) days. All CRS events resolved. Neurologic AEs potentially consistent with immune effector cell-associated neurotoxicity syndrome (ICANS), and considered treatment-related, occurred in two patients (Gr 1 ICANS and Gr 2 lethargy, each n=1); both events resolved. ICANS occurred one day after a Gr 2 CRS event. No Gr 5 (fatal) AEs, or AEs leading to treatment discontinuation were reported. AEs of special interest included infections (35.0%), neutropenia (15.0%), thrombocytopenia (20.0%), and tumor flare events (10.0%). Conclusions: In patients with R/R RT, fixed-duration mosunetuzumab monotherapy demonstrates activity with durable responses and a manageable safety profile in a limited sample size of 20 patients. Treatment with mosunetuzumab warrants further study in this patient population with a high unmet medical need.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| 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 | 0,000 |
| 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 | 0,001 |
| 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 source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».