Cyclophosphamide, Pomalidomide and Dexamethasone Significantly Improves Response over Poma/Dex in Relapsed/Refractory Myeloma Patients Previously Treated with Cyclophosphamide Combination Therapy - Initial Results of the Randomised Multicentre Mukseven Trial

• Published in: Blood 2018-11, Vol.132 (Supplement 1), p.3274-3274
• Main Authors: Croft, James, Hall, Andrew, Walker, Katrina, Sherborne, Amy L, Ellis, Sidra, Price, Amy, Sherratt, Debbie, Reed, Sadie, Pawlyn, Charlotte, Garg, Mamta, Boyd, Kevin, Cook, Gordon, Brown, Sarah R, Kaiser, Martin
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2018-99-111835

Background and aims Treatment of relapsed/refractory myeloma (RRMM) remains a challenge as most approved and commonly accessible doublet treatments induce responses (≥PR) in less than half of patients. The combination of the classical alkylator cyclophosphamide with thalidomide (CTD) or lenalidomide (CRD) is standard of care in early lines of therapy in the UK and elsewhere. Data on the clinical value of cyclophosphamide and pomalidomide combination therapy in RRMM is currently sparse and lacking for patients that have previously been treated with cyclophosphamide in earlier lines of therapy. Material and Methods MUKseven is a randomised phase II study for RRMM patients comparing cyclophosphamide (500 mg po d1, 8, 15), pomalidomide (4 mg days 1-21) and dexamethasone (40 mg; if ≥75 years 20 mg; d1, 8, 15, 21) (CPd) versus standard pomalidomide and dex (Pd). Patients with ≥2 prior lines of therapy were randomised 1:1 to receive either CPd or Pd and treated until progression. The primary endpoint of the study is PFS, secondary endpoints include response, OS and safety and toxicity. Patients underwent bone marrow sampling and peripheral blood collection at baseline, on treatment and at relapse to correlate outcomes with disease biology. The original sample size was 250 patients but due to approval of pomalidomide by the UK funding agency NICE mid-recruitment, and resulting low enrolment rates, a decision was made to close the trial early. Results In total 102 evaluable RRMM patients were randomised between March 2016 and February 2018, 51 each to CPd and Pd treatment arms that were comparable regarding age, gender, ISS and ECOG performance status. Patients had received a median of 3 prior lines of therapy (range 2-8); all had been treated with proteasome inhibitors and lenalidomide and 94% of patients had received cyclophosphamide as part of earlier lines of therapy. Trial entry criteria were permissive and allowed ongoing red cell, platelet and growth factor support to reflect real-world practice in RRMM - 11% of patients required platelet and 16% G-CSF support before starting trial therapy. Treatment with CPd was associated with a significantly higher response rate (≥PR) of 68.6% (95% CI: 54.1 - 80.9%) compared to 47.1% (CI: 32.9 - 61.5%) for Pd (P=0.018). Five patients (9.8%) on CPd treatment reached CR vs. none with Pd therapy (Table 1). PFS data is currently maturing and will be presented at the conference. At the time of abstract submission 20 patients w