Pomalidomide Plus Low-Dose Dexamethasone (Pom/Dex) in Relapsed Myeloma: Long Term Follow up and Factors Predicing Outcome in 345 Patients

Pomalidomide at doses of 2 or 4 mg/d has demonstrated excellent activity in patients with relapsed multiple myeloma (MM). Between November 2007 and March 2012, we opened 6 sequential phase 2 trials and treated 345 patients with relapsed MM with pomalidomide at differing doses with weekly dexamethasone (Pom/dex). Results of 164 of these patients have been previously published. Here we describe long term follow up of these patients as well as results of an additional 181 patients with relapsed MM treated with the Pom/dex regimen.

The six cohorts consisted of: Cohort 1 (N=60): relapsed MM with 1–3 prior regimens, 2 mg dose; Cohort 2 (N=34): lenalidomide (LEN) refractory, 2 mg dose; Cohort 3 (N=35): BZ)/LEN refractory, 2 mg dose; Cohort 4 (N=35): BZ/LEN refractory, 4 mg dose; Cohort 5 (N=60) LEN refractory, 1–3 prior regimens, 4 mg dose; and Cohort 6 (N=120) LEN refractory, 4 mg dose. Pomalidomide was given orally 2 mg daily or 4mg daily on days 1–28(cohorts 1–5) or 1–21 (cohort 6) of a 28-day cycle with oral dexamethasone given 40 mg daily on days 1, 8, 15 and 22. Response was assessed by the International Myeloma Working Group Uniform Response criteria. All patients received aspirin 325 mg daily for deep venous thrombosis (VTE) prophylaxis or full dose anticoagulation.

A total of 345 patients were enrolled across all 6 cohorts. One patient was ineligible and excluded from analysis. The median age was 64 years (32–88). The median time since diagnosis was 53 months. The median number of prior therapies was 3 (1–14). 147 (44%) had high-risk molecular markers by mSMART criteria. Prior therapies consisted of thalidomide 52%, lenalidomide 87%, bortezomib 75%, autologous stem cell transplant 70% and allogeneic transplant 3%. The median follow-up is 10.4 months (5.4–34 months). Sixty-seven percent are alive and 32% remain progression free. 46 patients are continuing to receive treatment. The most common toxicities (grade 3 or higher) were neutropenia (31%), anemia (16%), thrombocytopenia (12%), pneumonia (8%) and fatigue (8%). VTE was seen in 10 patients (3%). Outcomes are shown in Table 1. Across all 6 cohorts confirmed responses of partial response (PR) or better were seen in 34%. The response rate in all patients with mSMART high risk status was 30.6%. Responses and duration of response (DOR) in those with high risk molecular markers include: 17p– 19 of 56 (34%) DOR 8.2 months; t(4;14) 6 of 24 (25%) and DOR 4.8 months; t(14;16) 7 of 11(64%) and DOR 9.5 months; deletion 13 by cytogenetics 13 of 37 (35%) with DOR 8.2 months. In a multivariate analysis, only LDH > ULN, number of prior regimens, and prior BZ therapy were predictive of a shorter TTP and factors associated with a poor OS following initiation of pomalidomide therapy included B2M > 5.5, LDH > ULN,number of prior regimens, and prior BZ therapy.

Pom/dex is active and well tolerated even in heavily pretreated patients and those with high risk molecular markers. Remissions are durable. Response rates and toxicity are similar between the 2 mg and 4 mg doses.

Lacy:Celgene: Research Funding. Stewart:Celgene: Consultancy, Honoraria. Reeder:Celgene: Mayo Clinic receives funding from Celgene to support clinical trials Other, Research Funding.