Final results of a phase II study of lenalidomide-elotuzumab as maintenance therapy post-autologous stem cell transplant (AuSCT) in patients (Pts) with multiple myeloma (MM).
Authors: Thomas Sheeba K. , George Jamie S , Morales de Partovi Claudia M , Feng Lei , Morphey Ashley S , Becnel Melody R. , Kaufman Gregory P , Lee Hans C. , Manasanch Elisabet Esteve , Patel Krina K. , Pasvolsky Oren , Ye Jing Christine , Amini Behrang , Qazilbash Muzaffar H. , Bashir Qaiser , Crumpton Brandon N , Stafford Mildred M , Johnson III Ralph J , Weber Donna M , Orlowski Robert Z 
Published: June 2024

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Background: Randomized controlled trials oflenalidomide (LEN) maintenance after AuSCT have shown a progression free survival (PFS) benefit in pts with MM. We report final results of a phase 2 trial evaluating the efficacy and safety of adding elotuzumab (ELO) to LEN as maintenance therapy post- AuSCT. Methods: On 28-day cycles, patients received ELO 10mg/kg iv weekly for cycles 1-2.Between 4/15/2015-1/27/2016, 27 pts received ELO 10mg/kg q2 weeks for cycles 3-6 and 20mg/kg monthly for cycles 7+. From 1/28/2016 forward, 74 pts received ELO 20 mg/kg monthly from cycle 3+. LEN was dosed at 10 mg/day for cycles 1-3 and increased to 15 mg/day at physician discretion starting with cycle 4 in the absence of non-hematologic (HEME) toxicity > grade 1, ANC < 1000/mL and platelet count < 100K/ml. For the 1st 8 weeks, pts <75 yrs received 28 mg of dexamethasone (DEX) 3-24 hours pre-infusion and pts ≥75yrs received 8 mg; pts received 4-10 mg iv DEX pre-infusion for all cycles. Zoster and thromboembolic prophylaxis were prescribed as per standard recommendations. The primary endpoint was PFS, defined as time from AuSCT to progressive disease (PD) or death (whichever occurred first), or censored at last contact date. Secondary objectives were best response, overall survival (OS), incidence of second primary malignancies (SPMs) and adverse event (AE) profile. Enrollment was completed on 6/5/2019. Eligible pts received ≤2 induction lines of therapy (LOT) and were 60-210 days post-AuSCT. Results: Pts (n=100) were treated for a median of 40 cycles (2-109). With a median follow up of 74.3 mos, 78% of pts (n=79) remain alive. Median PFS was 75.4 months. Median OS has not been reached; 5-year OS rate was 86.7%. At study entry, rate of ≥VGPR was 77.3% and ≥CR was 37.7%. On study, this improved to 91.1% ≥VGPR and 69.3% ≥CR. Of pts in ≥VGPR and tested for minimal residual disease (10-5 sensitivity by flow cytometry), 37/44 were negative. High-risk cytogenetics (n=44; p<0.0001), International Staging System (ISS) Stage III (n=10/95, p=0.049) and Revised-ISS Stage III (n = 3/89; p= 0.026) predicted shorter median PFS (39.2, 53.2 and 32.2 mos. respectively). Median PFS on next LOT was 21.8 mos. Grade 3-4 HEME AEs (n=102) were: neutropenia 35%, thrombocytopenia 7%, and anemia 10% . Grade 3-4 non-HEME AEs in >3 pts were: respiratory infections 23%, hypophosphatemia 19%, diarrhea 13% , fatigue 11% , peripheral neuropathy 7%, other infections 6%, myalgias 4%, and high ALT 4%. Incidence of HEME, non-invasive and solid tumor SPMs was 8%, 8% and 7%. Median time to HEME SPM diagnosis was 45.5 mos. Conclusions: ELO-LEN is a well-tolerated maintenance therapy on which 53% of patients had improved quality of response. Median PFS and 5-year OS compare favorably with results from CALGB 100104 and IFM 2005-02 trials of lenalidomide alone. SPM incidence is similar to rates reported in these trials. Clinical trial information: NCT02420860 .