Safety and Efficacy of Pomalidomide Plus Low-Dose Dexamethasone (POM + LoDEX) in Patients (Pts) with Relapsed/Refractory Multiple Myeloma (RRMM) in Italy: A Subanalysis of the Stratus Trial (MM-010)
Authors: Cavo Michele , Corradini Paolo , Di Raimondo Francesco , Petrini Mario , Cafro Anna Maria , Caravita di Toritto Tommaso , Offidani Massimo , Semenzato Gianpietro , Zambello Renato , Lazzaro Antonio , Petrucci Maria Teresa , Rodeghiero Francesco , Simcock Mathew , Slaughter Ana , Herring Jennifer , Peluso Teresa , Palumbo Antonio 
Published: October 2019

Abstract
Introduction: For pts with RRMM who have failed or progressed on treatment (Tx) with newer agents, such as lenalidomide (LEN) and bortezomib (BORT), there are few Tx options, and overall survival (OS) is short (Kumar et al, Leukemia, 2012). POM is a distinct immunomodulatory agent with tumoricidal and immunoregulatory effects, and POM + LoDEX is approved in the United States and European Union for the Tx of pts with RRMM who have had ≥ 2 prior Tx, including LEN and BORT. Tx with POM + LoDEX has shown statistically greater survival benefits than high-dose DEX (MM-003; San Miguel et al, Lancet Oncol, 2013) or POM alone (MM-002; Richardson et al, Blood, 2014). POM + LoDEX has also demonstrated high overall response rates in pts with RRMM in the STRATUS trial (MM-010), a single-arm, open-label phase 3b study being conducted in 19 countries across Europe with a primary endpoint of safety (Dimopoulos et al, EHA 2015). Italian pts constituted the largest national subset in MM-010; hence, this subanalysis examines the safety and efficacy of POM + LoDEX in pts from Italy.
Patients and Methods: Pts with RRMM (progressive disease [PD] on or within 60 days of last prior Tx) who had experienced Tx failure with BORT and LEN and had received adequate prior alkylator therapy were eligible. Pts received POM 4 mg on days 1-21 of a 28-day cycle in combination with DEX 40 mg (20 mg for pts aged > 75 yrs) on days 1, 8, 15, and 22. Thromboprophylaxis was required for all pts, and Tx was continued until PD or unacceptable toxicity.
Results: A total of 219 pts were enrolled in MM-010 in Italy. The median age of this patient population was 67.0 yrs (range, 42-84 yrs), and 54.8% of pts were male. The median time since diagnosis was 5.5 yrs, and 37.0% of pts were International Staging System stage III. Patients were heavily pretreated, with a median of 4 prior anti-myeloma regimens (range, 2-11), and most pts were refractory to LEN (95%), BORT (82.2%), or both LEN and BORT (78.1%). As of May 4, 2015, 2 pts (0.9%) were not treated, 54 pts (24.7%) were still on treatment, and 163 pts (74.4%) had discontinued. After a median follow-up of 11.3 mos, in the intention-to-treat population, the overall response rate was 37.9% (range, 31.4%-44.7%), the median duration of response was 6.8 mos (95% CI, 4.9-10.8 mos), progression-free survival (PFS) was 5.2 mos (95% CI, 4.4-6.4 mos), and OS was 12.0 mos (95% CI, 10.6-15.2 mos). The most frequent grade 3/4 treatment-emergent AEs were neutropenia (56.7%), anemia (25.8%), thrombocytopenia (23.5%), and pneumonia (12.4%). Incidence of grade 3/4 venous thromboembolism (deep vein thrombosis and pulmonary embolism) and peripheral neuropathy were infrequent (2.3% and 0%, respectively). The most common reasons for discontinuation were disease progression (49.8%), death (10.0%), and adverse events (AEs; 5.0%). AEs led to dose reductions or interruptions of POM in 23.0% and 71.0% of pts, respectively, and the median relative dose intensity for POM was 0.90.
Conclusions: In line with previous studies, POM + LoDEX was active in Italian pts, a representative subset of the heavily pretreated MM-010 population. PFS and OS were consistent with those seen in previous trials. POM + LoDEX treatment was well tolerated, and discontinuations due to AEs were infrequent, consistent with the well-known toxicity profile and the appropriate drug management. This study confirms that POM + LoDEX is effective in patients with advanced RRMM, including those who have experienced failure of prior Tx with BORT and/or LEN.

Disclosures
Cavo: Janssen-Cilag, Celgene, Amgen, BMS: Honoraria. Petrini:Novartis: Research Funding; Celgene Corporation: Research Funding; Italfarmaco: Research Funding; Roche: Research Funding. Caravita di Toritto:Celgene Corporation: Honoraria, Research Funding. Offidani:Celgene, Janssen: Honoraria. Petrucci:Celgene Corporation: Honoraria; Janssen-Cilag: Honoraria; Amgen: Honoraria; Mundipharma: Honoraria; BMS: Honoraria. Rodeghiero:Celgene Corporation: Honoraria, Research Funding. Simcock:Celgene Corporation: Employment. Slaughter:Celgene Corporation: Employment, Equity Ownership. Herring:Celgene Corporation: Employment. Peluso:Celgene Corporation: Employment. Palumbo:Celgene, Millennium Pharmaceuticals, Amgen, Bristol-Myers Squibb, Genmab, Janssen-Cilag, Onyx Pharmaceuticals: Consultancy, Honoraria; Novartis, Sanofi Aventis: Honoraria.