A Phase II Study of Lenalidomide in Previously Untreated, Symptomatic Chronic Lymphocytic Leukemia (CLL).
Notice bibliographique
Résumé
Abstract Introduction: Lenalidomide is an immunomodulatory compound known to downregulate VEGF and TNFa; stimulate production of inhibitory cytokines such as IL-2; and modulate activity of T cells and natural killer cells. These effects form the basis for investigation of lenalidomide in CLL. Promising results from 2 studies in relapsed/refractory CLL have been reported (Chanan-Khan et al J Clin Oncol 2006; Ferrajoli et al ASH 2006). To date, there are no reports using lenalidomide in previously untreated CLL. We present preliminary data on 12 patients (pts) enrolled in an ongoing phase II study of single-agent lenalidomide in previously untreated, symptomatic CLL. Methods: Eligible pts must have histologically confirmed CLL; no prior therapy (excluding steroids alone for autoimmune cytopenias); and symptomatic disease (any of symptomatic adenopathy/organomegaly, cytopenias, constitutional symptoms, lymphocyte doubling count <12 mos). Starting dose for lenalidomide: 10mg daily with weekly 5mg dose escalations to the target dose of 25mg daily × 21 days every 28 day cycle. Prophylactic allopurinol and ASA are mandated. Steroids are allowed for management of tumor flare symptoms but routine prophylaxis is not used. Results: In October 2006, accrual was initiated. Two pts were enrolled at the starting dose of 10mg daily. Pt 1 reached the target dose of 25 mg with a lymphocyte reduction from 152 to 25 but at 6 weeks developed acute tumor lysis with renal failure and was removed from study. Pt 2 developed grade 4 neutropenia on cycle 1 day 21 leading to a septic death. The study was halted and the protocol was revised with reduced starting and target doses (2.5mg and 10mg, days 1–21), slower dose escalations (2.5mg cycle 1, 5mg cycle 2, 10mg cycle 3 and thereon), and extension of allopurinol tumor lysis prophylaxis to minimum 3 cycles. Upon study reactivation in March 2007, 10 pts have been accrued. Median age 61(range 33–71), 5 pts with Rai stage III–IV, baseline median Hb 109g/L (range 80–158), platelets 180×109/L (range 43–233), lymphocytes 70×109/L (range 3.4–190), β2microglobulin 214 nmol/L (range 139–498; normal <170). Eight pts have received at least 1 cycle and are evaluable for toxicity. Hematologic toxicity: 5/8 pts developed Gr 3–4 neutropenia, leading to dose reductions in 3 pts and hospitalization for febrile neutropenia in 1 pt. Gr 4 thrombocytopenia developed at the 10mg dose in 1 pt. Nonhematologic toxicity: Gr 1–2 fatigue(5), tumor flare(4), non-desquamating rash(3), and infections(3) are most common. Tumor flare (painful, enlarged nodes often associated with nasal congestion/scalp pruritis) can occur with each dose escalation but is responsive to short course prednisone. No further episodes of tumor lysis have been noted. Responses: Dramatic lymphocyte reductions at as early as 1 week are seen, with 6 of 8 pts (75%) achieving a partial response (PR), all by end of cycle 2 (using ≤5mg doses). Phosphoproteomic and microarray studies from blood samples at baseline and during treatment will be presented. Conclusion: Preliminary data from this ongoing phase II study suggests that lenalidomide has significant activity in previously untreated CLL patients. Toxicities such as tumor lysis, tumor flare and myelosuppression are common and mandate a more conservative dosing regimen than previously used in relapsed/refractory CLL or myeloma. Responses seen at low doses (≤5mg daily) are encouraging.
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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 | 0,001 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,001 | 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) | 0,000 | 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 ».