A story of nourishment, serendipity, and the unexpected bonds that connect us with patients.

This essay is about how caring for my complicated father with amyotrophic lateral sclerosis (ALS) unexpectedly shaped how I approached my work as a gynecologic oncologist.

Multiple myeloma (MM) and related malignancies develop from an asymptomatic precursor condition, monoclonal gammopathy of undetermined significance (MGUS), detectable via blood testing. The benefits and harms of population-based MGUS screening remain uncertain. We conducted a nationwide screening study for monoclonal gammopathies and a randomized trial of follow-up strategies in Iceland (Iceland Screens, Treats, or Prevents Multiple Myeloma; ClinicalTrials.gov identifier: NCT03327597). In total, 75,422 (53% of those invited) were screened and those with MGUS (n = 3,541) were randomly assigned to no notification (arm 1), guideline-based follow-up (arm 2), or intensified follow-up (arm 3). Progression, symptom burden, and psychological well-being were compared between the control arm (arm 1) and intervention arms (arms 2 and 3). After a median follow-up of 4.5 years, screening led to a 27-fold increase in the detection of smoldering MM (8.6% v 0.3%; hazard ratio, 27.46 [95% CI, 10.21 to 73.86]; P < .001), but active malignancy rates did not differ. Active MM and related malignancy were diagnosed 1 year earlier in the intervention arms with fewer symptomatic presentations and hospitalizations at diagnosis. MGUS notification was not associated with adverse psychological outcomes. These findings demonstrate that population-based screening facilitates earlier detection of MM and expands access to early intervention without detectable psychological harm. Longer follow-up is required to determine the effects on survival and cost-effectiveness.

The TRIANGLE trial established an ibrutinib-containing therapy without autologous stem-cell transplantation (ASCT) as the new standard for younger, treatment-naïve patients with mantle cell lymphoma (MCL). However, the benefit of rituximab maintenance (RM) within this novel standard is unclear. We investigated whether RM improves progression-free survival (PFS) and overall survival (OS) with acceptable toxicity when added to the experimental arms of TRIANGLE. This secondary analysis of TRIANGLE included patients randomly assigned to ibrutinib-containing therapy without (I) or with (A + I) ASCT who responded to induction/ASCT. RM was given per national and center practice. PFS and OS of patients with and without RM were compared with inverse probability of treatment weighted Kaplan-Meier curves and log-rank tests. Among responders after induction/ASCT (I: 274; A + I: 237), RM was given to 61% (I) and 64% (A + I). RM prolonged PFS in ibrutinib-containing treatment arms (I: log-rank test: P = .003, 4-year PFS probability RM v no RM, 85% v 73%; A + I: P < .001, 90% v 75%). There were trends toward prolonged OS in RM groups. RM groups were at higher risk of grade 3 to 5 infectious toxicity (I: 34% v 11%; A + I: 41% v 18%). Our findings support adding RM to BTK inhibitor treatments in younger, untreated patients with MCL to achieve prolonged remission.

Over the past three decades, the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer has undergone a remarkable transformation. Once associated with poor outcomes and a median survival of <2 years in the metastatic setting, HER2-positive metastatic breast cancer is at present increasingly managed for years, with long-term survival beyond 5 years becoming common. Parallel advances in early-stage therapy have substantially reduced recurrence rates and altered the clinical landscape of metastatic disease, with a growing proportion of patients currently presenting with de novo metastatic disease rather than relapse after prior HER2-directed treatment. These improvements have been driven by successive generations of HER2-targeted therapies, including monoclonal antibodies, tyrosine kinase inhibitors, and antibody-drug conjugates. Most recently, trastuzumab deruxtecan (T-DXd) has demonstrated unprecedented efficacy and is rapidly moving earlier in treatment algorithms across both metastatic and curative-intent settings. This shift raises important questions regarding optimal sequencing, toxicity management-particularly for interstitial lung disease-and the downstream implications for other HER2-directed therapies. In this review, we summarize the evolution of HER2-targeted therapy and discuss strategies for managing HER2-positive breast cancer across disease stages in the era of earlier treatment with T-DXd.