0000000000476366
AUTHOR
Gregor Verhoef
Five-Year Follow-up of Patients Receiving Imatinib for Chronic Myeloid Leukemia
The cause of chronic myeloid leukemia (CML) is a constitutively active BCR-ABL tyrosine kinase. Imatinib inhibits this kinase, and in a short-term study was superior to interferon alfa plus cytarabine for newly diagnosed CML in the chronic phase. For 5 years, we followed patients with CML who received imatinib as initial therapy.We randomly assigned 553 patients to receive imatinib and 553 to receive interferon alfa plus cytarabine and then evaluated them for overall and event-free survival; progression to accelerated-phase CML or blast crisis; hematologic, cytogenetic, and molecular responses; and adverse events.The median follow-up was 60 months. Kaplan-Meier estimates of cumulative best …
Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia.
Imatinib, a selective inhibitor of the BCR-ABL tyrosine kinase, produces high response rates in patients with chronic-phase chronic myeloid leukemia (CML) who have had no response to interferon alfa. We compared the efficacy of imatinib with that of interferon alfa combined with low-dose cytarabine in newly diagnosed chronic-phase CML.We randomly assigned 1106 patients to receive imatinib (553 patients) or interferon alfa plus low-dose cytarabine (553 patients). Crossover to the alternative group was allowed if stringent criteria defining treatment failure or intolerance were met. Patients were evaluated for hematologic and cytogenetic responses, toxic effects, and rates of progression.Afte…
Safety and Clinical Activity of the Anti-CD22 Immunoconjugate Inotuzumab Ozogamicin (CMC-544) in Combination with Rituximab in Follicular Lymphoma or Diffuse Large B-Cell Lymphoma: Preliminary Report of a Phase 1/2 Study
Abstract Inotuzumab ozogamicin (CMC-544) is an antibody-targeted chemotherapy agent composed of a humanized CD22 antibody, conjugated to calicheamicin, a potent cytotoxic antitumor agent. Inotuzumab ozogamicin targets B-cell malignancies since they often express CD22. In a previously reported phase 1 dose-escalation trial in patients with CD22-positive B-cell non-Hodgkin’s lymphoma (NHL), the maximum tolerated dose (MTD) was determined to be 1.8 mg/m2 every 4 weeks. Responses were seen in patients with both follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL). This ongoing study consisted of a limited dose escalation (DE) portion to confirm the MTD of inotuzumab ozogamicin whe…
Phase III Study to Evaluate Temsirolimus Compared With Investigator's Choice Therapy for the Treatment of Relapsed or Refractory Mantle Cell Lymphoma
Purpose Temsirolimus, a specific inhibitor of the mammalian target of rapamycin kinase, has shown clinical activity in mantle cell lymphoma (MCL). We evaluated two dose regimens of temsirolimus in comparison with investigator's choice single-agent therapy in relapsed or refractory disease. Patients and Methods In this multicenter, open-label, phase III study, 162 patients with relapsed or refractory MCL were randomly assigned (1:1:1) to receive one of two temsirolimus regimens: 175 mg weekly for 3 weeks followed by either 75 mg (175/75-mg) or 25 mg (175/25-mg) weekly, or investigator's choice therapy from prospectively approved options. The primary end point was progression-free survival (P…
Safety and clinical activity of a combination therapy comprising two antibody-based targeting agents for the treatment of non-Hodgkin lymphoma: results of a phase I/II study evaluating the immunoconjugate inotuzumab ozogamicin with rituximab.
Purpose Inotuzumab ozogamicin (INO) is an antibody-targeted chemotherapy agent composed of a humanized anti-CD22 antibody conjugated to calicheamicin, a potent cytotoxic agent. We performed a phase I/II study to determine the maximum-tolerated dose (MTD), safety, efficacy, and pharmacokinetics of INO plus rituximab (R-INO) for treatment of relapsed/refractory CD20+/CD22+ B-cell non-Hodgkin lymphoma (NHL). Patients and Methods A dose-escalation phase to determine the MTD of R-INO was followed by an expanded cohort to further evaluate the efficacy and safety at the MTD. Patients with relapsed follicular lymphoma (FL), relapsed diffuse large B-cell lymphoma (DLBCL), or refractory aggressive NH…
Supportive Efficacy Analyses for the Phase 3 Study of Temsirolimus Versus Investigator’s Choice Therapy for the Treatment of Patients with Relapsed or Refractory Mantle Cell Lymphoma.
Abstract Temsirolimus (Torisel®) is a specific inhibitor of the mTOR kinase with antitumor activity in patients with relapsed or refractory mantle cell lymphoma. In a phase 3, randomized, open-label study, patients treated with temsirolimus 175 mg weekly 3 times followed by 75 mg weekly (175/75-mg) had significantly longer progression-free survival (PFS) than those treated with investigator’s choice therapy (p-value temsirolimus: investigator’s choice = 0.0009; hazard ratio = 0.44; 97.5% CI = 0.25, 0.78; Hess et al. J Clin Oncol.2008, 28:abs 8513). Patients treated with temsirolimus 175 mg weekly 3 times followed by 25 mg weekly (175/25-mg) showed a trend towards longer PFS than those treat…