47 research outputs found

    Melflufen or pomalidomide plus dexamethasone for patients with multiple myeloma refractory to lenalidomide (OCEAN): a randomised, head-to-head, open-label, phase 3 study

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    Background Melphalan flufenamide (melflufen), an alkylating peptide-drug conjugate, plus dexamethasone showed clinical activity and manageable safety in the phase 2 HORIZON study. We aimed to determine whether melflufen plus dexamethasone would provide a progression-free survival benefit compared with pomalidomide plus dexamethasone in patients with previously treated multiple myeloma. Methods In this randomised, open-label, head-to-head, phase 3 study (OCEAN), adult patients (aged ≥18 years) were recruited from 108 university hospitals, specialist hospitals, and community-based centres in 21 countries across Europe, North America, and Asia. Eligible patients had an ECOG performance status of 0–2; must have had relapsed or refractory multiple myeloma, refractory to lenalidomide (within 18 months of randomisation) and to the last line of therapy; and have received two to four previous lines of therapy (including lenalidomide and a proteasome inhibitor). Patients were randomly assigned (1:1), stratified by age, number of previous lines of therapy, and International Staging System score, to either 28-day cycles of melflufen and dexamethasone (melflufen group) or pomalidomide and dexamethasone (pomalidomide group). All patients received dexamethasone 40 mg orally on days 1, 8, 15, and 22 of each cycle. In the melflufen group, patients received melflufen 40 mg intravenously over 30 min on day 1 of each cycle and in the pomalidomide group, patients received pomalidomide 4 mg orally daily on days 1 to 21 of each cycle. The primary endpoint was progression-free survival assessed by an independent review committee in the intention-to-treat (ITT) population. Safety was assessed in patients who received at least one dose of study medication. This study is registered with ClinicalTrials.gov, NCT03151811, and is ongoing. Findings Between June 12, 2017, and Sept 3, 2020, 246 patients were randomly assigned to the melflufen group (median age 68 years [IQR 60–72]; 107 [43%] were female) and 249 to the pomalidomide group (median age 68 years [IQR 61–72]; 109 [44%] were female). 474 patients received at least one dose of study drug (melflufen group n=228; pomalidomide group n=246; safety population). Data cutoff was Feb 3, 2021. Median progression-free survival was 6·8 months (95% CI 5·0–8·5; 165 [67%] of 246 patients had an event) in the melflufen group and 4·9 months (4·2–5·7; 190 [76%] of 249 patients had an event) in the pomalidomide group (hazard ratio [HR] 0·79, [95% CI 0·64–0·98]; p=0·032), at a median follow-up of 15·5 months (IQR 9·4–22·8) in the melflufen group and 16·3 months (10·1–23·2) in the pomalidomide group. Median overall survival was 19·8 months (95% CI 15·1–25·6) at a median follow-up of 19·8 months (IQR 12·0–25·0) in the melflufen group and 25·0 months (95% CI 18·1–31·9) in the pomalidomide group at a median follow-up of 18·6 months (IQR 11·8–23·7; HR 1·10 [95% CI 0·85–1·44]; p=0·47). The most common grade 3 or 4 treatment-emergent adverse events were thrombocytopenia (143 [63%] of 228 in the melflufen group vs 26 [11%] of 246 in the pomalidomide group), neutropenia (123 [54%] vs 102 [41%]), and anaemia (97 [43%] vs 44 [18%]). Serious treatment-emergent adverse events occurred in 95 (42%) patients in the melflufen group and 113 (46%) in the pomalidomide group, the most common of which were pneumonia (13 [6%] vs 21 [9%]), COVID-19 pneumonia (11 [5%] vs nine [4%]), and thrombocytopenia (nine [4%] vs three [1%]). 27 [12%] patients in the melflufen group and 32 [13%] in the pomalidomide group had fatal treatment-emergent adverse events. Fatal treatment-emergent adverse events were considered possibly treatment related in two patients in the melflufen group (one with acute myeloid leukaemia, one with pancytopenia and acute cardiac failure) and four patients in the pomalidomide group (two patients with pneumonia, one with myelodysplastic syndromes, one with COVID-19 pneumonia). Interpretation Melflufen plus dexamethasone showed superior progression-free survival than pomalidomide plus dexamethasone in patients with relapsed or refractory multiple myeloma.Oncopeptides ABPeer reviewe

    Plain language summary of the MajesTEC-1 study of teclistamab for the treatment of people with relapsed or refractory multiple myeloma

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    The authors acknowledge the patients and investigators who participated in this study, in addition to the staff members at the study sites, the Data Review and Safety Monitoring Committees, Alliance Foundation Trials (AFT; https://acknowledgments.alliancefound.org), and the Janssen Team. This work was funded by Janssen Oncology. The MajesTEC-1 study was sponsored by Janssen Oncology and designed in partnership with AFT. Editorial and medical writing support were provided by Carolyn Farnsworth, Katie Yoest, PhD, and Katie Veleta, PhD, of MedThink SciCom and were funded by Janssen Global Services, LLC. Financial & competing interests disclosureThe authors' full disclosure information can be found in the original research article. Writing support for this summary was provided under the direction of the author(s) by Katie Yoest, PhD, and Katie Veleta, PhD, of MedThink SciCom and was funded by Janssen Research and Development. Open accessWhat is this summary about? This is a summary of a phase 1-2 clinical trial called MajesTEC-1. This trial tested the cancer drug teclistamab in people with relapsed or refractory multiple myeloma, a cancer that forms in a certain type of white blood cells known as plasma cells. Most participants who took part in the study had at least 3 prior treatments for multiple myeloma before their cancer came back. How was the study in this summary conducted? A total of 165 participants from 9 countries were included in this study. All participants were given teclistamab once per week and monitored for side effects. Once participants started taking teclistamab, they were checked regularly to monitor if their cancer had no change, improved (responded to treatment), or worsened or spread (known as disease progression). What were the results of the study? After approximately 14.1 months of follow-up (from 2020 to 2021), 63% of participants who were given teclistamab had a decrease in myeloma burden, meaning that they responded to treatment with teclistamab. Participants who responded to teclistamab lived without their myeloma coming back for approximately 18.4 months. The most common side effects were infections, cytokine release syndrome, abnormally low white and red blood cell counts (neutropenia, lymphopenia, and anemia), and low platelet cell counts (thrombocytopenia). Approximately 65% of participants experienced serious side effects. What do the results of this study mean? Overall, more than half of the participants (63%) in the MajesTEC-1 study responded to treatment with teclistamab despite previous myeloma treatment failures. Clinical Trial Registration: NCT03145181, NCT04557098 (ClinicalTrials.gov) </sec

    A real world multicenter retrospective study on extramedullary disease from Balkan Myeloma Study Group and Barcelona University: analysis of parameters that improve outcome

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    Here, we report the outcome of 226 myeloma patients presenting with extramedullary plasmacytoma or paraosseous involvement in a retrospective study conducted in 19 centers from 11 countries. Extramedullary disease was detected at diagnosis or relapse between January 2010 and November 2017. Extramedullary plasmacytoma and paraosseous involvement were observed in 130 patients at diagnosis (92 of 38) and in 96 at relapse (84 of 12). The median time from multiple myeloma diagnosis to the development of extramedullary disease was 25.1 months (range 3.1-106.3 months) in the relapse group (median follow up: 15 months). Imaging approach for extramedullary disease was computed tomography (n=133), positron emission tomography combined with computed tomography (n=50), or magnetic resonance imaging (n=35). The entire group received a median two lines of treatment and autologous stem cell transplantation (44%) following the diagnosis of extramedullary disease. Complete response was higher for paraosseous involvement versus extramedullary plasmacytoma at diagnosis (34.2% vs. 19.3%; P=NS.) and relapse (54.5% vs. 9%; P=0.001). Also paraosseous involvement patients had a better progression-free survival (PFS) when recognized at initial diagnosis of myeloma than at relapse (51.7 vs. 38.9 months). In addition, overall survival was better for paraosseous involvement compared to extramedullary plasmacytoma at diagnosis (not reached vs. 46.5 months). Extramedullary plasmacytoma at relapse had the worst prognosis with a PFS of 13.6 months and overall survival of 11.4 months. In the multivariate analysis, paraosseous involvement, extramedullary disease at diagnosis, International Staging System (ISS-I), and undergoing autologous stem cell transplantation improved overall survival independently. This cohort demonstrated that extramedullary disease benefits from front-line autologous stem cell transplantation and extramedullary plasmacytoma differs from paraosseous involvement in terms of rate and duration of response, with even worse outcomes when detected at relapse, constituting an unmet clinical need
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