Gracia Martınez

BACKGROUND: Belantamab mafodotin had single-agent activity in patients with relapsed or refractory multiple myeloma, a finding that supports further evaluation of the agent in combination with standard-care therapies. METHODS: In this phase 3, open-label, randomized trial, we evaluated belantamab mafodotin, bortezomib, and dexamethasone (BVd), as compared with daratumumab, bortezomib, and dexamethasone (DVd), in patients who had progression of multiple myeloma after at least one line of therapy. The primary end point was progression-free survival. Key secondary end points were overall survival, response duration, and minimal residual disease (MRD)-negative status. RESULTS: In total, 494 patients were randomly assigned to receive BVd (243 patients) or DVd (251 patients). At a median follow-up of 28.2 months (range, 0.1 to 40.0), median progression-free survival was 36.6 months (95% confidence interval [CI], 28.4 to not reached) in the BVd group and 13.4 months (95% CI, 11.1 to 17.5) in the DVd group (hazard ratio for disease progression or death, 0.41; 95% CI, 0.31 to 0.53; P<0.001). Overall survival at 18 months was 84% in the BVd group and 73% in the DVd group. An analysis of the restricted mean response duration favored BVd over DVd (P<0.001). A complete response or better plus MRD-negative status occurred in 25% of the patients in the BVd group and 10% of those in the DVd group. Grade 3 or higher adverse events occurred in 95% of the patients in the BVd group and 78% of those in the DVd group. Ocular events were more common in the BVd group than in the DVd group (79% vs. 29%); such events were managed with dose modifications, and events of worsening visual acuity mostly resolved. CONCLUSIONS: As compared with DVd therapy, BVd therapy conferred a significant benefit with respect to progression-free survival among patients who had relapsed or refractory multiple myeloma after at least one line of therapy. Most patients had grade 3 or higher adverse events. (Funded by GSK; DREAMM-7 ClinicalTrials.gov number, NCT04246047; EudraCT number, 2018-003993-29.).

Chronic hepatitis C is often a progressive liver disease for which there is no satisfactory treatment. We studied the efficacy of recombinant α-interferon or γ-interferon in the treatment of this disease in comparison with a control group. Thirty patients were randomly assigned to three groups. Ten patients received 7.5 MU α-interferon/m 2 body surface three times weekly for 3 mo, then 5 MU/m 2 for 3 mo and 2.5 MU/m 2 for 6 mo. Ten patients were treated with γ-interferon at a dose of 2 MU/m 2 for 6 mo and the other 10 served as controls without treatment. The mean serum ALT levels and liver histological findings improved significantly only in the patients treated with α-interferon. No changes were observed in patients treated with γ-interferon or in controls. Five of 10 patients treated with α-interferon had complete responses (mean ALT normal during therapy). After treatment ALT returned to pretreatment levels in two of 5 patients. The long-term response rate after α-interferon therapy was 30% at 18 mo. We conclude that α-interferon is effective in controlling disease activity in a portion of patients with chronic hepatitis C. High doses of α-interferon do not appear to add further benefit in the response rate or relapse rate. γ-Interferon therapy is ineffective. (Hepatology 1991;13:327-331).

Longer-term outcomes with the anti-CD38 antibody isatuximab in combination with carfilzomib-dexamethasone (Isa-Kd) were evaluated in the randomized Phase 3 trial IKEMA (NCT03275285), in a prespecified, follow-up analysis of progression-free survival (PFS, primary study endpoint), final complete response (CR) using Hydrashift Isa immunofixation assay, minimal residual disease (MRD) negativity, and safety. Enrolled patients had relapsed/refractory multiple myeloma (1-3 prior treatment lines). Isa 10 mg/kg was administered intravenously weekly in cycle 1 then biweekly. Efficacy analyses were performed in the intent-to-treat population (Isa-Kd: n = 179, Kd: n = 123) and safety evaluated in treated patients (Isa-Kd: n = 177, Kd: n = 122). Consistent with the primary interim analysis, the addition of Isa to Kd prolonged PFS (HR 0.58, 95.4% CI: 0.42-0.79; median PFS 35.7 [95% CI: 25.8-44.0] vs 19.2 [95% CI: 15.8-25.0] months). PFS benefit was observed with Isa-Kd across subgroups, including patients with poor prognosis. The stringent CR/CR rate was 44.1% vs 28.5% (odds-ratio: 2.09, 95% CI: 1.26-3.48), the MRD negativity rate 33.5% vs 15.4% (odds-ratio: 2.78, 95% CI: 1.55-4.99) and the MRD negativity CR rate 26.3% vs 12.2%, with Isa-Kd vs Kd. The safety profile of Isa-Kd was similar to that reported in the prior interim analysis. These findings further support Isa-Kd as a standard-of-care treatment for relapsed multiple myeloma patients.Clinical trial information: ClinicalTrials.gov, NCT03275285.