An Experience on Pomalidomide in Patients within Relapsed/Refractory Multiple Myeloma - A Multicenter Study in Turkey

Objective: Pomalidomide is a new generation thalidomide analogue. Effectiveness as a single agent or combination with low dose dexamethasone has been in the treatment of relapse/refractory Multiple Myeloma (MM). The aim of the present study was to share the experience of different oncology centres with pomalidomide treatment in patients with relapsed/refractory MM. Materials and Methods: Seventy-three patients from 16 centres were enrolled into the study. The patients were followed for a median of 6 months. Relapsed/refractory MM patients who received at least one line of treatment before pomalidomide were included into the study. ISS, R-ISS and Eastern Cooperative Oncology Group (ECOG) scores of the patients and treatment-related side effects were evaluated. Results: As a result of the median follow-up for 6 months, 36% (26/72) of the patients presented progression. The estimated median PFS was found 29 months. The Cox regression analysis revealed that ECOG affected PFS only, myeloma subtype; ISS and R-ISS scores did not affect PFS. The most common side effects with pomalidomide treatment in our population include neutropenia, infections, anaemia and thrombocytopenia. Conclusion: In our study, it was statistically shown that the ECOG score was effective in survival in relapsed / refractory MM patients treated by pomalidomide. Therefore, we recommend evaluation of the ECOG score for each patient before treatment in eligible cases.

Lenalidomide and irinotecan in adults with recurrent malignant gliomas: Phase I results of the phase I/II trial.

2036 Background: Patients with recurrent malignant gliomas have limited treatment options. We previously reported promising results using 6 month progression free survival [PFS6] endpoint combining irinotecan and thalidomide compared to historical controls. In this study, we tested the tolerability and efficacy of Irinotecan combined with Lenalidomide, a more potent thalidomide analogue with unique antiangiogenic and immunomodulatory properties. Methods: This phase I portion of the phase I/II study aimed to determine the maximum tolerated doses (MTD) of irinotecan and lenalidomide. Eligible patients were adults (>=18 y) with recurrent WHO Grade 3 or 4 gliomas who were not on EIAED, had failed prior radiation therapy, had a KPS>=60, had adequate marrow, renal and hepatic organ function, no major medical illnesses and no other concurrent malignancies. Each cycle was designated as 4 weeks in duration. Results: Two of the 4 patients enrolled at the starting dose level of Lenalidomide 10 mg/day on days 1-21 and irinotecan 200 mg/m2 q2 weeks developed rash as dose limiting toxicity (DLT). The trial was restarted with no change in irinotecan dose but with a lowered Lenalidomide dose of 7.5 mg/day for cycle 1 with escalation to 10 mg/day for cycle 2 and beyond. Of 3 eligible patients enrolled, no DLTs were noted even after cycle 2. The dose was hence escalated to Lenalidomide 10 mg/day with unchanged irinotecan dose. Only 1/6 patients experienced a DLT (pulmonary embolism); however, it was noted that 4/6 patients required dose reduction of irinotecan to 150 mg/m2 after cycle 1. One patient died during cycle 2 of unknown causes (autopsy declined) without reports of preceding toxicities. Non DLT toxicities included neutropenia, leukopenia, hypokalemia, diarrhea, fatigue and nausea/vomiting. Lenalidomide pharmacokinetic data, obtained by serial blood draws initially after one dose of the drug on day 0 and subsequently after irinotecan and lenalidomide dose on day 1 to examine drug interactions, will be presented. Conclusions: Based on these results, the maximum tolerated dose was Lenalidomide 10 mg/day on days 1-21 and irinotecan 150 mg/m2 q 2 weeks every 28 days which will be used in the phase II study that will open shortly.