Efficacy and Safety of Pomalidomide As a Replacement Therapy for Lenalidomide for Relapsed/Refractory Multiple Myeloma Patients Refractory to a Lenalidomide-Containing Combination Regimen

Introduction

Pomalidomide (POM) is an immunomodulatory drug shown to be safe and effective for the treatment of relapsed/refractory multiple myeloma (RRMM) patients (pts) previously treated with bortezomib and lenalidomide. POM in combination with dexamethasone has been shown to overcome resistance and to be effective not only in RRMM pts but also in high risk myeloma cases. In this trial, we are evaluating the efficacy, safety and tolerability of POM replacing lenalidomide for pts who were refractory to a lenalidomide and steroid-containing regimen that includes at least one other agent.

Methods

This is a multicenter, open-label and non-randomized study. MM pts who were refractory to a combination regimen containing lenalidomide, steroids and at least one other agent were treated with the same regimen except POM replaced lenalidomide. For regimens containing bortezomib, carfilzomib, clarithromycin, cyclophosphamide, and/or pegylated liposomal doxorubicin, pts received 4 mg of POM from the beginning of the trial. Patients who had failed regimens containing ixazomib, elotuzumab or daratumumab for which the MTD of POM was unknown underwent intra-patient dose escalation from a POM dose of 2, 3 and 4 mg during Cycles 1, 2 and 3, respectively. POM was administered daily on days 1-21 of a 28-day cycle for a maximum of 8 cycles whereas the other drugs were administered using the same schedule(s), dose(s) and drug combination as the last lenalidomide-containing regimen that the patient received and failed. The planned enrollment for the study is 45 pts.

Results

To date, a total of 32 pts have been enrolled. All pts have completed at least one full cycle of treatment. Currently, 11 pts are still active and 21 pts have discontinued treatment. The median age of all pts was 70 years (range, 52-81 years), and 20 (64%) were males. Pts received a median of 3 prior treatments (range, 1-7). The median follow-up time for all pts is 5.3 months (range, 0.9-8.1). Of the evaluable pts, 16 (50%) and 16 (50%) received 2 mg and 4 mg as their starting dose of POM, respectively. Of the 16 pts that received 4 mg of POM, 6 (38%), 8 (50%) and 2 (12%) were on bortezomib, clarithromycin, and carfilzomib-containing regimens, respectively. For thee 16 pts with the starting dose of 2 mg of POM, 13 (81%), 2 (13%) and 1 (6%) were on elotuzumab, daratumumab and ixazomib-containing treatments, respectively.

Among all 32 evaluable pts, four (12.5%) pts achieved PR or better (1=CR, 1=PR and 2=VGPR), four (12.5%) pts achieved MR, 15 (47%) pts showed stable disease (SD), while 9 (28%) pts exhibited disease progression.

At the time of data cutoff, the overall response (ORR) and clinical benefit rates (CBR) were 12.5% and 25%, respectively. ORR and CBR are expected to improve with further follow up among patients who have been recently enrolled on this trial. The median progression free survival was 7.6 months. Common ≥ Grade 3 adverse events were neutropenia (10%), hypomania (4%) and leukopenia (4%).

Conclusions

We show thatPOM replacement for lenalidomide among RRMM pts who are refractory to a lenalidomide and steroid-containing regimen that includes at least one other agent achieves clinical activity in some patients.