Motixafortide and G-CSF to mobilize hematopoietic stem cells for autologous transplantation in multiple myeloma: a randomized phase 3 trial.

Autologous hematopoietic stem cell transplantation (ASCT) improves survival in multiple myeloma (MM). However, many individuals are unable to collect optimal CD34+ hematopoietic stem and progenitor cell (HSPC) numbers with granulocyte colony-stimulating factor (G-CSF) mobilization. Motixafortide is a novel cyclic-peptide CXCR4 inhibitor with extended in vivo activity. The GENESIS trial was a prospective, phase 3, double-blind, placebo-controlled, multicenter study with the objective of assessing the superiority of motixafortide + G-CSF over placebo + G-CSF to mobilize HSPCs for ASCT in MM. The primary endpoint was the proportion of patients collecting ≥6 × 106 CD34+ cells kg-1 within two apheresis procedures; the secondary endpoint was to achieve this goal in one apheresis. A total of 122 adult patients with MM undergoing ASCT were enrolled at 18 sites across five countries and randomized (2:1) to motixafortide + G-CSF or placebo + G-CSF for HSPC mobilization. Motixafortide + G-CSF enabled 92.5% to successfully meet the primary endpoint versus 26.2% with placebo + G-CSF (odds ratio (OR) 53.3, 95% confidence interval (CI) 14.12-201.33, P < 0.0001). Motixafortide + G-CSF also enabled 88.8% to meet the secondary endpoint versus 9.5% with placebo + G-CSF (OR 118.0, 95% CI 25.36-549.35, P < 0.0001). Motixafortide + G-CSF was safe and well tolerated, with the most common treatment-emergent adverse events observed being transient, grade 1/2 injection site reactions (pain, 50%; erythema, 27.5%; pruritis, 21.3%). In conclusion, motixafortide + G-CSF mobilized significantly greater CD34+ HSPC numbers within two apheresis procedures versus placebo + G-CSF while preferentially mobilizing increased numbers of immunophenotypically and transcriptionally primitive HSPCs. Trial Registration: ClinicalTrials.gov , NCT03246529.

What is the price of survival in Hodgkin's lymphoma? Long-term follow-up of cured patients.

The paper investigates the late complications of cured Hodgkin's lymphoma (HL) patients. Ninety cured HL patients between 1975 and 1994 were examined. The mean ages of patients at the time of diagnosing HL, and the median period of survival after diagnosis were 32 (11-70) years and 18 (10-30) years, respectively. Among the 90 patients, 73 are still alive, there is no information about 9 and 8 patients died, second malignant disease being the cause of death in 4 of them. Relapse was observed in 24 patients, of which 19 recovered after relapse and were included in the study then. Five patients had late relapse. In 38% of patients, cardiovascular changes, while in 32% pulmonary and pleural damages were observed. Disorders of the thyroid gland, overwhelmingly hypothyroidism, were found in 24%. Less frequently, a second malignant tumour (9%), damage to the skin, musculature, bones and genitourinary system (6%) as well as the gastrointestinal system could be detected. Treatment based on modern therapeutic approaches is expected to decrease the incidence of complications. Still the aim is early detection through close patient follow-up, which may improve the quality of life and decrease mortality as a result.