28 research outputs found
A randomized placebo-controlled phase II study of clarithromycin or placebo combined with VCD induction therapy prior to high-dose melphalan with stem cell support in patients with newly diagnosed multiple myeloma
Abstract Background The objective of this randomized placebo-controlled study was to investigate the efficacy and safety of clarithromycin in combination with bortezomibâcyclophosphamideâdexamethasone (VCD) in patients with newly diagnosed multiple myeloma eligible for high-dose therapy. Methods Patients were randomized to receive tablet clarithromycin 500 mg or matching placebo tablet twice daily during the first 3 cycles of VCD induction therapy. Primary endpoint was to compare the rate of very good partial response (VGPR) or better response after three cycles of VCD combined with clarithromycin or placebo. Results The study was prematurely stopped for safety reasons after the inclusion of 58 patients (36% of the planned study population). The patients were randomly assigned to clarithromycin (nâ=â27) or placebo (nâ=â31). VGPR or better response after the VCD induction therapy was obtained in 12 patients (44.4%, 95% CI 25.5â64.7) and in 16 patients (51.6%, 33.1â69.8) (pâ=â0.59) in the clarithromycin group and the placebo group, respectively. Seven patients (25.9%) in the clarithromycin group developed severe gastrointestinal complications (âĽâgrade 3) comprising pain, neutropenic enterocolitis, paralytic ileus or peptic ulcer. These complications occurred in only one patient in the placebo group. Septicemia with Gram negative bacteria was observed in 5 patients in the clarithromycin group in contrast to one case of pneumococcal septicemia in the placebo group. Patient-reported QoL were negatively affected in the clarithromycin group compared to the placebo group. Conclusion The study was prematurely stopped due to serious adverse events, in particular serious gastrointestinal complications and septicemia. The response data do not suggest any effect of clarithromycin when added to the VCD regimen. The combination of clarithromycin and bortezomib containing regimens is toxic and do not seem to offer extra anti-myeloma efficacy. Trial registration EudraCT (no. 2014-002187-32, registered 7 October 2014, https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-002187-32/DK) and ClinicalTrials.gov (no NCT02573935, retrospectively registered 12 October 2015, https://www.clinicaltrials.gov/ct2/show/NCT02573935?term=Gregersen&cntry=DK&rank=9
Nationwide implementation of lenalidomide maintenance in multiple myeloma: A retrospective, realâworld study
Abstract Lenalidomide maintenance (LM) has shown benefit in progressionâfree survival (PFS) and overall survival (OS) in clinical trials. LM is the recommended standard of care in patients with newly diagnosed multiple myeloma (MM) after highâdose melphalan and autologous stem cell transplantation (HDMâASCT). In Denmark, LM has been approved and publicly funded for all patients treated with HDMâASCT since June 2019. Patients with newly diagnosed MM treated with their first HDMâASCT between June 2019 and March 2022 were included and followed until data cutâoff in June 2023. To compare outcomes, a historical preâLM cohort from the Danish MM Registry, consisting of 364Â MM patients treated with HDMâASCT between June 2015 and June 2019, was used. Among 364 patients treated with HDMâASCT after June 2019, 22.3% received consolidation therapy and 3.7% underwent tandem HDMâASCT. During followâup, 297 patients (81.6%) initiated maintenance therapy, with 277 (76.1%) receiving LM. Overall, 145 patients (52.3%) discontinued LM most commonly due to toxicity 75 (51.7%), with fatigue (30.7%), cytopenia (25.3%), and neuropathy (17.3%) being the main reasons. In a 6âmonth landmark analysis, early discontinuation did not negatively impact PFS or OS. The LM cohort had similar PFS, and OS compared to the preâLM cohort. The 3âyear PFS and OS rates in the LM cohort were 61% and 86%, respectively, while the preâLM cohort had a 3âyear PFS of 55% and a 3âyear OS of 89%. In conclusion, the introduction of LM as a nationwide treatment option in Denmark did not lead to improved clinical outcomes