Time-to-Event Analysis of Polatuzumab Vedotin-Induced Peripheral Neuropathy to Assist in the Comparison of Clinical Dosing Regimens.

Polatuzumab vedotin, an antibody-drug conjugate containing monomethyl auristatin E, was associated with an incidence of grade ≥2 peripheral neuropathy (PN) of 55-72% in patients with indolent non-Hodgkin lymphoma in a phase II study, when dosed 1.8-2.4 mg/kg every 3 weeks until progression or for a maximum of 17 cycles. To quantify the correlation of conjugate exposure and treatment duration with PN risk, a time-to-event model was developed using data from phase I and II studies. The model suggested that PN risk increased with conjugate exposure and treatment cycles, and a trend for increased risk with body weight and albumin concentration. When capping the treatment duration to six to eight cycles, the risk ratio of a dose of 2.4 mg/kg vs. 1.8 mg/kg was ≥1.29; the predicted incidence of grade ≥2 PN at 1.8-2.4 mg/kg dose levels was 17.8-37.2%, which is comparable with other antimicrotubule agents for lymphoma treatment.

Cyclosporine experience in nephrotic syndrome.

OBJECTIVE: To analyze the use of Cyclosporine (CyA) in nephrotic syndrome. METHODS: Thirty five children of mean age of 5.9 years with steroid dependent (n = 26) or steroid resistant (n = 9) primary nephrotic syndrome with normal renal functions and who received CyA were studied. CyA was used at a dosage of 6-7 mg/kg/day orally in two divided doses. The mean duration of therapy was 9.6 weeks. All received a minimum of 8 weeks of CyA therapy. In a few who received longer therapy, the dose was reduced to 4 mg/kg/day. All patients were monitored serially for hepatotoxicity and nephrotoxicity. The nephrotic state was evaluated serially with biochemical tests and followed up for a mean period of 2.55 years. RESULTS: Thirty one patients completed the study. The response to therapy was categorized into 5 groups-no response (4 patients), good response (4 patients), partial response (4 patients), cyclosporine dependence (16 patients), and infrequent relapsers (3 patients). Good response was defined as complete remission lasting for at least one year after cessation of therapy. Patients who showed partial response had reduction in quantitative proteinuria and needed less diuretics. Sixteen patients went into complete remission while on therapy but relapsed within 3 months of discontinuation (CyA dependence). The response to CyA correlated more with steroid-responsiveness than with the underlying histopathology. The drug was well tolerated. CONCLUSION: In steroid-dependent or steroid-resistant nephrotic children with normal renal functions, CyA therapy may be considered as one of the possible therapeutic options. Our results suggest that a longer duration of CyA therapy may possibly be indicated in these cases.