Pomalidomide and Dexamethasone Is an Effective Regimen for Advanced-Stage Relapsed/Refractory Multiple Myeloma: Experience of a Single Center
Authors: Jimenez Zepeda Victor H , Duggan Peter , Neri Paola E. , Bahlis Nizar J 
Published: October 2019

Abstract
Introduction Almost all patients with MM eventually relapse, and the remission duration in relapsed MM decreases with each regimen. Pomalidomide is an IMiD with antiproliferative, anti-inflammatory and anti-angiogenic effects that was recently approved for the use of relapsed MM failing lenalidomide and bortezomib. Based on these findings, we aimed to evaluate the efficacy of pomalidomide and dexamethasone (PD) for heavily-pretreated relapsed or refractory MM (RRMM) at our Institution. Methods We retrospectively reviewed the records of all patients with RRMM treated with PD at Tom Baker Cancer Center between 01/10 and 06/14. Eligible patients were age 18 years or older; had RRMM after two or more prior therapies (including lenalidomide, bortezomib or thalidomide); and had an Eastern Cooperative Group performance status of 0 to 2. Patients received oral pomalidomide 2-4 mg/d on days 1-21, and dexamethasone 20 mg or 40 mg on a weekly basis. Definitions of response and progression were used according to the EBMT modified criteria. The primary endpoint of the study was to assess the efficacy and feasibility of PD in this group of patients. All analyses were performed using the SPSS 20.0 software and all p-values were 2-sided and statistically significant if <0.05 Results Between 01/10 and 06/14, 31 patients were identified for the study. Clinical and laboratory characteristics are listed in Table 1.The median age for this cohort of patients was 64 years (46-81). Seventy-one percent of patients had IgG isotype, 19.4% had IgA, and 9.7% had light chain only disease. The median number of therapies prior to PD was 4 (2-11). All patients received lenalidomide and bortezomib prior to PD; 11 patients had bortezomib, 8 had lenalidomide and 7 had both prior to PD. Six patients out of 11 receiving bortezomib prior to PD responded (54%) versus 12.5% (1/8), 14% (1/7), and 20% (1/5) for those receiving lenalidomide, lenalidomide/bortezomib and other regimens respectively prior to PD. (p=0.07) Two patients received pomalidomide at a dose of 3 mg, 1 at 2 mg and 28 at 4 mg. After a median of 5 cycles, the ORR was 29% (9/31) with 1 patient achieving nCR and 8 patients (25.8%) PR. (Table 2 ) The median time to first response was 8 weeks with majority of cases achieving at least PR after 2 cycles of therapy. Stable disease was seen in 22.6% and progression in 29% of cases. FISH cytogenetics at relapse were available in 24 patients with 6 cases exhibiting high risk disease (25%). At a median follow-up of 20 months, 16 patients (51.6%) are alive and 21 (67.7%) had already progressed. Median OS was 19.1 months and median PFS 5.6 months. Median PFS was 6.5 months in the group with SR cytogenetics compared to 3.1 months for the HR group. (p0.2) Median OS was similar between SR and HR (19.4 vs 23 months) (p=0.14) With regards to toxicity, 9 patients experienced grade 3/4 hematological toxicity. Eight patients required blood transfusion and one patient discontinued therapy due to grade 4 thrombocytopenia. In conclusion, Pomalidomide is an efficacious drug for the treatment of RRMM. The current report confirms the ORR seen in previous studies and the benefit in HR disease. Further combinations with pomalidomide in the setting of HR disease and for those patients who immediately progressed on IMiD therapies should be considered.
Table 1. Clinical and Laboratory characteristics for RRMM patients treated with Pomalidomide and Dexamethasone Characteristic N Median Range % Age (years) 31 64 46-81 Gender -Male -Female 14 17 45.2% 54.8% ISS Stage I II III 5 14 12 16.1% 45.2% 38.7% Heavy chain IgG IgA Free light chain only Light chainKappa Lambda 22 6 3 25 6 71% 19.4% 9.7% <![if !supportEmptyParas]> <![endif]> 80.6% 19.4% Hemoglobin (g/L) 31 113 75-142 Creatinine (µmol/L) 31 86 50-290 Calcium (µmol/L) 31 2.3 2.06-2.64 LDH (IU/L) 31 189 84-489 B2-microglobulin (mg/L) 31 4.2 1.36-16.3 Albumin (g/L) 31 33 21-42 BMPC (%) 31 30 8-98 FISH Cytogenetics Standard risk High risk 24 18 6 75% 25% Prior Therapies ASCT Thalidomide Lenalidomide Bortezomib Carfilzomib 21 13 31 31 6 67.7% 41.9% 100% 100% 19.4%
Table 2. Response rates for RRMM patients treated with Pomalidomide and Dexamethasone Characteristic Median (Range) N % Number of cycles 5 (1-31) Overall Response rate 9/31 29% Near Complete Response Complete Response 1 0 3.2% 0% Very Good Partial Response 0 0% Partial Response 8 25.8% Stable Disease 7 22.6% Minimal Response 6 19.4% Progression 9 29% Alive 16 51.6%

Disclosures
Jimenez Zepeda: Janssen Ortho: Honoraria. Bahlis:Celgene: Honoraria, Research Funding.