Efficacy and Tolerability of Lenalidomide/Dexamethasone in Intensively Pretreated Myeloma Patients: Experiences from the German Named Patient Program.

Lenalidomide (Len), an immunomodulatory drug, in combination with dexamethasone (Dex) is a new treatment option for patients (pts) with relapsed or refractory multiple myeloma (MM). Reimbursement and drug laws in Germany allow treatment before marketing authorization of a given drug, if no alternatives are available for life-threatening diseases. AIM: To evaluate efficacy and tolerability of MM pts treated with Len/Dex in the German named patient (pt) program.

PATIENT AND METHODS: A comprehensive, previously tested, questionnaire was used to document data from consecutive pt series in five large and specialized university treatment centres. Response was assessed using the EBMT criteria.

RESULTS: 55 pts were documented so far (median age, 63 yrs; 92% stage III Durie & Salmon). Pts were heavily pretreated: 30% had up to 2 previous therapy lines, 35% had three, 13% four and 21% more than four; the median no. was 3 (interquartile range, IQR 2–4). Pts had received a median of 16 (IQR 10–22) previous courses of chemotherapy. Forty-nine patients (89%) had previously received a stem cell transplant (SCT): 41 an autologous and an additional eight allogeneic SCT. That correlates with a 2-fold higher proportion of pts with prior SCT compared to the Len registration trial. Furthermore, the proportion of pts treated with the new drugs thalidomide or bortezomib was even 7–10-fold higher than in the registration trial. Best response could be assessed in 49 pts.: 4% CR, 32% PR, 19% MR, thereby showing an overall reponse rate of 55%. Four patients (8%) progressed during therapy and two (4%) died before response evaluation. The table shows response in different subgroups according to previous therapies. Response (CR/PR/MR) ranged from 88% (7/8) with only 1 previous treatment line shown in the table to 52% (16/31) with 2–3 and 43% (6/14) with 4–5. The most common adverse event III°/IV° was infection occurring in 21/55 (38%) patients. Thrombo-embolic events were observed in three patients (5%). Haematological toxicity grade IV° was seen in 11/46 (24%) patients, most common in course 1 of therapy. Five patients (9%) died during treatment, four due to infection (one in neutropenia) and one patient due to cerebral bleeding. 70% of patients were alive at last follow-up.

CONCLUSION: In this pt cohort Len/Dex induced considerable antineoplastic activity despite extensive pretreatment. Toxicity was moderate and as expected for this risk-cohort. Nevertheless pts with more than 3 prior treatment lines should receive close clinical monitoring in order to prevent life-threatening infection.