Enduring Responses after 1-Year, Fixed-Duration Cevostamab Therapy in Patients with Relapsed/Refractory Multiple Myeloma: Early Experience from a Phase I Study
Notice bibliographique
Résumé
Background: Relapsed/refractory multiple myeloma (RRMM) remains an incurable disease, with most treatment regimens continued until disease progression (PD). New treatments that are efficacious when given for a fixed duration and offer the potential for an extended treatment-free period may also decrease cumulative toxicities and reduce the burden of treatment on both patients and healthcare systems. Cevostamab is an FcRH5xCD3 T-cell engaging bispecific monoclonal antibody that facilitates T-cell directed killing of myeloma cells and has demonstrated clinically meaningful activity and a favorable toxicity profile when given Q3W for up to 17 cycles (approximately 1 year) in an ongoing Phase I trial (GO39775; NCT03275103) in patients with heavily pre-treated RRMM (Trudel et al. ASH 2021). Here, we report early duration of response data for patients in GO39775 who completed 17 cycles of cevostamab and stopped treatment. Methods: All patients were aged ≥18 years and had RRMM for which no established therapy was available, appropriate, or tolerable, and an ECOG performance status of 0-1. Cevostamab was administered by intravenous infusion in 21-day cycles with step-up dosing in Cycle (C) 1 for cytokine release syndrome mitigation. Treatment was continued for 17 cycles (approximately 1 year) unless PD or unacceptable toxicity occurred. Patients who achieved a partial response (PR) or better by C17 and maintained a response through C17 were included in the analysis. Results: At data cut-off (March 8, 2022), a total of 16 patients (median age: 66.5 years; range: 45-80) completed C17 of cevostamab treatment and were eligible for analysis. Patients had received a median of 6 prior lines of therapy (range: 2-11), with 12 patients having received ≥5 prior therapies. Thirteen patients were triple-class refractory and 11 were penta-refractory. Fifteen patients were refractory to their last prior therapy. Five patients had received prior anti-B-cell maturation antigen (BCMA) targeted therapies, 4 of whom were refractory to anti-BCMA treatment. Patients received cevostamab target doses ranging from 40-160mg and received a median of 17 cycles of treatment (range: 16-17). Among the 16 patients analyzed, the best overall response (BOR) achieved was: stringent complete response (sCR) in 7 patients, CR in 3 patients, very good partial response (VGPR) in 5 patients, and PR in 1 patient. At data cut-off, 13 of the 16 patients remained in remission, with 8 patients (BOR: 5 sCR, 1 CR, 2 VGPR) maintaining a response ≥6 months after completion of therapy and 3 patients (BOR: 2 sCR, 1 CR) maintaining a response ≥12 months after completion of therapy. Eight patients had <6 months of follow-up. None of the patients (0/10) who completed C17 and attained a sCR or CR had relapsed. Only 3 of the 16 patients (BOR: 2 VGPR, 1 PR) had PD after the completion of C17 of cevostamab. Time to progression following completion of therapy for the 2 patients who achieved a VGPR was 7.8 months and 12.9 months. For the patient who achieved a PR, time to progression was 1.3 months. Due to its mechanism of action, treatment with cevostamab may be associated with an increased risk of infection. Infections occurred in 2 patients after the completion of C17 of cevostamab therapy. Pneumonia was reported in both patients, with onset after the last dose of 1.3 months and 3.8 months. Both events resolved and both patients have remained on study. Conclusions: Early data from this Phase I study suggest that patients can maintain durable responses (≥6 months) after completion of 17 cycles of cevostamab treatment, highlighting the potential for an extended treatment-free period following fixed-duration therapy. Further data are needed to confirm the duration of response and associated correlates following completion of treatment. Additional data on responding patients with premature discontinuation of treatment (i.e. prior to completion of C17) and patients retreated with cevostamab will be presented.
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 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) | 0,000 | 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 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 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.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».