Five years on, intensified therapy still separates high-risk myeloma from its historical control

The edition in brief

OPTIMUM/MUKnine gave 107 patients with newly diagnosed high-risk myeloma daratumumab-based quadruplet induction, transplant, extended two-part consolidation and daratumumab-lenalidomide maintenance, and compared them with 120 molecularly matched patients from Myeloma XI. At five years, median progression-free survival was not reached against 24.4 months (HR 0.32, 95% CI 0.22 to 0.45) and overall survival not reached against 57.4 months (HR 0.43, 0.28 to 0.65). The control is external and its follow-up nearly twice as long, so era effects and later salvage options are uncontrolled; the benefit did not hold in patients with three or more high-risk cytogenetic abnormalities. A meta-analysis of 22 studies and 12,173 patients puts claudin 18.2 positivity at the validated threshold of 75% or more moderate-to-strong membranous staining at 33.99% (30.13 to 38.07) of gastric and gastro-oesophageal junction adenocarcinoma, with heterogeneity of 92.4% and a prediction interval of roughly 18% to 55% — the authors warn it is not a zolbetuximab eligibility figure. Six randomised trials of long-term exercise during anthracycline chemotherapy in 360 women with breast cancer found attenuation of troponin I rise (SMD −0.50, −0.93 to −0.06) but no difference in ejection fraction, global longitudinal strain, troponin T or NT-proBNP; the cardioprotective claim remains unproven. The FDA approved a supplement to the vemurafenib application on 20 August 2026; the record does not state what changed, so check Drugs@FDA before telling a patient anything about their treatment has. And ASTCT has updated its consensus grading for immune effector cell toxicities, revising the criteria for cytokine release syndrome, ICANS and IEC-HS and adding definitions for haematotoxicity, non-ICANS neurological syndromes, enterocolitis, tumour inflammation-associated neurotoxicity and on-target off-tumour effects.