Improvement in Clinical Benefit Parameters with Pomalidomide (POM) in Combination with Low-Dose Dexamethasone (LoDEX) in Patients with Relapsed and Refractory Multiple Myeloma (RRMM): Results From a Phase 2 Study
Authors: Lonial Sagar , Baz Rachid , Bahlis Nizar J. , Chen Christine I. , Anderson Kenneth C. , Chen Min , Zaki Mohamed , Richardson Paul G. 
Published: October 2019

Abstract
Abstract 4052

Background:
In patient (pts) with advanced MM, clinical parameters such as low platelet count and high serum creatinine levels carry poor prognosis (Kumar SK, et al. Mayo Clin Proc. 2004;79:867-74). At this disease stage, outcome of MM therapy should be assessed not only with the traditional parameters (progression-free survival, duration of response, and overall survival), but also by evaluating meaningful clinical parameters. POM a novel immunomodulatory agent, in combination with LoDEX, has demonstrated encouraging clinical activity and favorable tolerability in pts with RRMM in the multicenter, randomized, open-label MM-002 phase 1/2 study (Richardson PG, et al. Blood 2011;118:abs 634). This study evaluated changes in clinically important disease parameters with potential prognostic significance; data from the cut-off date of 30 March 2012 are presented.

Methods:
Pts with MM and ≥2 prior therapies including LEN and BORT, and disease progression during or within 60 days of their last treatment, were randomized to POM+LoDEX (POM, 4 mg/day for days 1–21 of a 28-day cycle (C); LoDEX, 40 mg/week) or POM alone. At progression, patients receiving Pom alone could receive POM+LoDEX at the discretion of the investigatior. All pts received mandatory thromboprophylaxis (daily low-dose aspirin). We herein present the effect of POM+LoDEX on end-organ functional parameters, including platelet count, serum calcium, serum creatinine (SCr), albumin (Alb), residual nonaffected normal immunoglobulins (Ig) (other than M-protein), hemoglobin (Hgb), and ECOG performance status. Improvement from baseline parameters was assessed by evaluating the change in end-organ functional parameters from pre-therapy to best post-therapy levels. Improvement was defined as a shift from abnormal to normal, with a normal platelet count defined as 150–350 × 103/mm3; calcium level 8.3–10.6 mg/dL; SCr level 0.9–1.5 mg/dL; increase of serum Alb ≥0.5 g/dL; Ig levels: IgA >70 mg/dL, IgG >565 mg/dL, and IgM >40 mg/dL; Hgb increase ≥1 g/dL; and decrease in ECOG performance status of at least 1 score. No allowance was made for the possible confounding influence of the use of blood or platelet transfusions.

Results:
Of the 113 pts who were randomized to receive POM+LoDex, 112 pts were evaluable for safety. Median number of prior therapies was 5, median treatment duration with POM+LoDEX was 5.0 months, and median number of cycles was 5. A substantial number of pts had abnormal baseline platelet count, calcium, SCr, and Ig levels (Table). During POM+LoDEX treatment, platelet counts, calcium, and SCr levels improved in 62%, 93%, and 42% of pts with abnormal values at baseline, respectively. Most pts treated with POM+LoDEX (97%) had low IgA, IgG, or IgM at baseline. Of those pts, Ig levels improved into a normal range in 15% of pts. Hgb levels increased by ≥1 g/dL in 30% of pts by the end of C2, 41% by C4, and 50% by C8. Alb levels increased by ≥0.5 g/dL in 5% of pts by C2, 8% by C4, and 15% by C8. At baseline, 29 pts in the POM+LoDEX group had an ECOG score of 0, 66 pts had a score of 1 and 10 pts had a score of 2. During treatment, 2 of the 10 pts with a score of 2 improved to 1 and 1 improved to a score of 0; 6 pts maintained their baseline score of 2, 1 pt deteriorated from score 2 to 4. Of those with a baseline score of 1, 22 pts improved to a score of 0, 41 maintained their score of 1 and 3 pts deteriorated (2 to a score of 2 and 1 to a score of 5). Twenty-three pts maintained their ECOG score of 0; 6 pts deteriorated to a score of 1. Overall, there was no incidence of grade 3 or 4 peripheral neuropathy and there was a low overall incidence of hypercoagulable events 4% (2% DVT and 2% PE). Therefore disease parameters associated with these adverse events were not assessed.

Conclusions:
Treatment with POM+LoDEX is associated with an improvement in clinically important disease parameters including, platelet count, serum calcium, SCr, Alb, Ig, and Hgb. ECOG status also normalized or improved in 33% of pts. Improvements in end-organ functional parameters may improve the prognosis and facilitate clinical benefit for advanced RRMM pts, with the ability to continue effective therapy enhanced accordingly – an observation which warrants further clinical study, both comparatively and in combination with other active agents in this setting.

Disclosures:
Lonial: Millennium, Celgene, Novartis, BMS, Onyx, Merck; all < $10,000 per year and disclosed to my institution: Consultancy. Off Label Use: Pomalidomide is an investigational drug and is not approved for the treatment of patients with any condition. Baz:Celgene, Millennium, Bristol Myers Squibb, Novartis: Research Funding. Bahlis:Celgene: Honoraria; Johnson and Johnson: Honoraria, Research Funding. Chen:Johnson & Johnson, Celgene, GlaxoSmithKline: Research Funding; Johnson & Johnson, Lundbeck, Celgene: Consultancy; Roche: Honoraria. Anderson:Acetylon, Oncopep: Scientific Founder, Scientific Founder Other; Celgene, Millennium, BMS, Onyx: Membership on an entity's Board of Directors or advisory committees. Chen:Celgene: Employment, Equity Ownership. Zaki:Celgene: Employment, Equity Ownership. Richardson:Celgene, Millennium, Johnson & Johnson: Advisory Board Other.