Does low-molecular-weight heparin influence the antimyeloma effects of thalidomide? A retrospective analysis of data from the GIMEMA, nordic and turkish myeloma study groups

Background/Aim: Low-molecular-weight heparin (LMWH) has been shown to prolong survival among patients with solid tumors, but its role among myeloma patients is unknown. Patients: Data from the GIMEMA (Gruppo Italiano Malattie Ematologiche dell'Adulto), Nordic and Turkish myeloma study groups comparing melphalan and prednisolone with (MPT, n: 404) or without thalidomide (MP, n: 393) are analyzed for effects of LMWH. Forty percent (159/394) of the patients on MPT and 7.4% (29/390) in the MP arm received LMWH. Results: Thalidomide improved response and progression-free survival (PFS). Regardless of thalidomide treatment, response rate was higher among those receiving LMWH vs. none vs. other anticoagulants (58.1 vs. 44.9 vs. 50.4%, p = 0.01). PFS was significantly longer (median 32 vs. 21 and 17 vs. 17 months, p = 0.004) only among international scoring system (ISS) I patients receiving MPT +/- LMWH vs. MP +/- LMWH. The group of MPT patients who also received LMWH had a better OS compared to those who did not [45 months, 95% confidence interval (CI) 27.7-62.3, vs. 32 months, 95% CI 26.1-37.9; p = 0.034]. When multivariate analysis was repeated in subgroups, thalidomide was no longer a significant factor (response, PFS) among those receiving LMWH. Conclusion: Addition of LMWH to MPT, in particular in patients with low ISS, suggests additive effects, but the results are limited by the retrospective design of our study. (C) 2015 S. Karger AG, Base

Antibody interference and response kinetics of isatuximab plus pomalidomide and dexamethasone in multiple myeloma

The ICARIA-MM study was sponsored by Sanofi. The authors thank, Helgi van de Velde, Valérie Boutet, Shujia Dai, Deborah DiNoto, Graziella Engelvin, Olivier Fedeli, Sébastien Hugla, Dominique Mouret, Béatrice Pradeilles, and Alain Roccon, all employees of Sanofi, for their contribution to the study, technology, and comments on the manuscript. The authors thank the participating patients and their families, and the study centers and investigators, for their contributions to the study. The medical writing support was provided by John Clarke, PhD and Stephanie Brillhart, PhD of Elevate Medical Affairs, contracted by Sanofi Genzyme for publication support services

Daratumumab plus pomalidomide and dexamethasone versus pomalidomide and dexamethasone alone in previously treated multiple myeloma (APOLLO): an open-label, randomised, phase 3 trial

Background: In a phase 1b study, intravenous daratumumab plus pomalidomide and dexamethasone induced a very good partial response or better rate of 42% and was well tolerated in patients with heavily pretreated multiple myeloma. We aimed to evaluate whether daratumumab plus pomalidomide and dexamethasone would improve progression-free survival versus pomalidomide and dexamethasone alone in patients with previously treated multiple myeloma. Methods: In this ongoing, open-label, randomised, phase 3 trial (APOLLO) done at 48 academic centres and hospitals across 12 European countries, eligible patients were aged 18 years or older, had relapsed or refractory multiple myeloma with measurable disease, had an Eastern Cooperative Oncology Group performance status of 0–2, had at least one previous line of therapy, including lenalidomide and a proteasome inhibitor, had a partial response or better to one or more previous lines of antimyeloma therapy, and were refractory to lenalidomide if only one previous line of therapy was received. Patients were randomly assigned (1:1) by an interactive web-response system in a random block size of two or four to receive pomalidomide and dexamethasone alone or daratumumab plus pomalidomide and dexamethasone. Randomisation was stratified by number of previous lines of therapy and International Staging System disease stage. All patients received oral pomalidomide (4 mg, once daily on days 1–21) and oral dexamethasone (40 mg once daily on days 1, 8, 15, and 22; 20 mg for those aged 75 years or older) at each 28-day cycle. The daratumumab plus pomalidomide and dexamethasone group received daratumumab (1800 mg subcutaneously or 16 mg/kg intravenously) weekly during cycles 1 and 2, every 2 weeks during cycles 3–6, and every 4 weeks thereafter until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival in the intention-to-treat population. Safety was analysed in all patients who received at least one dose of study medication. This trial is registered with ClinicalTrials.gov, NCT03180736. Findings: Between June 22, 2017, and June 13, 2019, 304 patients (median age 67 years [IQR 60–72]; 161 [53%] men and 143 [47%] women) were randomly assigned to the daratumumab plus pomalidomide and dexamethasone group (n=151) or the pomalidomide and dexamethasone group (n=153). At a median follow-up of 16·9 months (IQR 14·4–20·6), the daratumumab plus pomalidomide and dexamethasone group showed improved progression-free survival compared with the pomalidomide and dexamethasone group (median 12·4 months [95% CI 8·3–19·3] vs 6·9 months [5·5–9·3]; hazard ratio 0·63 [95% CI 0·47–0·85], two-sided p=0·0018). The most common grade 3 or 4 adverse events were neutropenia (101 [68%] of 149 patients in the daratumumab plus pomalidomide and dexamethasone group vs 76 [51%] of 150 patients in the pomalidomide and dexamethasone group), anaemia (25 [17%] vs 32 [21%]), and thrombocytopenia (26 [17%] vs 27 [18%]). Serious adverse events occurred in 75 (50%) of 149 patients in the daratumumab plus pomalidomide and dexamethasone group versus 59 (39%) of 150 patients in the pomalidomide and dexamethasone group; pneumonia (23 [15%] vs 12 [8%] patients) and lower respiratory tract infection (18 [12%] vs 14 [9%]) were most common. Treatment-emergent deaths were reported in 11 (7%) patients in the daratumumab plus pomalidomide and dexamethasone group versus 11 (7%) patients in the pomalidomide and dexamethasone group. Interpretation: Among patients with relapsed or refractory multiple myeloma, daratumumab plus pomalidomide and dexamethasone reduced the risk of disease progression or death versus pomalidomide and dexamethasone alone and could be considered a new treatment option in this setting. Funding: European Myeloma Network and Janssen Research and Development.European Myeloma Network and Janssen Research and Development

Health-related quality of life in patients with relapsed/refractory multiple myeloma treated with pomalidomide and dexamethasone ± subcutaneous daratumumab: Patient-reported outcomes from the APOLLO trial

In the phase 3 APOLLO trial, daratumumab in combination with pomalidomide and dexamethasone (D-Pd) significantly reduced the rate of disease progression or death by 37% relative to Pd alone in patients with relapsed/refractory multiple myeloma (RRMM) who had received ≥1 prior line of therapy including lenalidomide and a proteasome inhibitor. Here, we present patient-reported outcomes (PROs) from APOLLO. Median treatment duration was 11.5 months with D-Pd and 6.6 months with Pd. PRO compliance rates were high and similar in both groups. No changes from baseline were observed for EORTC QLQ-C30 global health status scores in either group, while physical and emotional functioning, disease symptoms, and adverse effects of treatment remained at baseline levels with D-Pd but worsened with Pd. Reductions (p < 0.05) in pain and fatigue were seen at several time points with D-Pd versus Pd. Overall, these results suggest patients' health-related quality of life remained stable when daratumumab was added to Pd, with several results favoring D-Pd versus Pd. These findings complement the significant clinical improvements observed with D-Pd and support its use in patients with RRMM.The APOLLO study was sponsored by the European Myeloma Network (EMN) in collaboration with Janssen Research & Development, LLC. Medical writing and editorial support were provided by Justine Lempart, PhD, and Linda V. Wychowski, PhD, of Eloquent Scientific Solutions and were funded by Janssen Global Services, LL

Current Multiple Myeloma Treatment Strategies with Novel Agents: A European Perspective

This review presents an overview of the most recent data using the novel agents thalidomide, bortezomib, and lenalidomide in the treatment of multiple myeloma and summarizes European treatment practices incorporating these novel agents

Daratumumab monotherapy for patients with intermediate-risk or high-risk smoldering multiple myeloma: a randomized, open-label, multicenter, phase 2 study (CENTAURUS)

n/