THE ROUNDS REPORT
RSV vaccines actually prevent hospitalizations. We finally have Level 1 evidence from 131,000 adults proving it.
The last three months delivered another slew of breakthrough trials. We're talking first-in-class therapies for conditions where we've been stuck for decades, combination regimens that double survival, and guideline updates that affect half your patient panel.
As usual, we try to distill only the most significant practice-changing data that shift treatment algorithms and spark debate amongst your colleagues.
Let’s get to it.
THE BIG FIVE GAME-CHANGERS
1. DAN-RSV: First Large Trial Proves RSV Vaccine Prevents Hospitalization
The DAN-RSV trial provided Level 1 evidence that RSV vaccination prevents hospitalization in adults ≥60 years.
131,379 adults in Denmark were randomized to bivalent RSVpreF vaccine (Abrysvo) versus no vaccine during the 2024-2025 RSV season. RSV hospitalization: 3 events versus 18 (vaccine effectiveness 83.3%; P=0.007). RSV lower respiratory tract hospitalization: effectiveness 91.7% (P=0.009).
This pragmatic, real-world RCT with hard hospitalization endpoints—not just symptomatic infection—establishes the clinical benefit of RSV vaccination in older adults.
2. FINE-ONE: First Evidence-Based Add-On Therapy for Type 1 Diabetes Nephropathy
Finerenone achieved 25% greater UACR reduction beyond ACEi/ARB in Type 1 diabetes with CKD.
242 patients with T1D, CKD (eGFR 25-<90), and UACR 200 to <5000 on background RAAS blockade received finerenone 10-20mg daily versus placebo. At 6 months, UACR reduction: geometric mean ratio 0.75 (P<0.001). ≥30% UACR reduction: 54.3% versus 32.7%. Hyperkalemia: 10.1% versus 3.3% (manageable in most cases).
This represents the first proven therapy beyond RAAS blockade for T1D nephropathy, filling a critical treatment gap.
3. FLAURA2: First-Line Osimertinib Plus Chemotherapy Extends Survival in EGFR-Mutated Lung Cancer
557 patients with previously untreated EGFR-mutated advanced NSCLC were randomized to osimertinib plus platinum-pemetrexed versus osimertinib monotherapy. The combination extended median overall survival to 47.5 months compared to 37.6 months with osimertinib alone (HR 0.77; P=0.02).
That's nearly 10 additional months of life, translating to a 23% reduction in mortality risk. Progression-free survival also improved: 25.5 months versus 16.7 months (HR 0.62).
The tradeoff: grade 3+ adverse events occurred in 70% of combination patients versus 34% with osimertinib alone. Most were reversible hematologic toxicities.
This establishes combination therapy as the new standard for fit patients with EGFR-mutated advanced NSCLC, fundamentally changing first-line treatment.
4. ALLEGORY: Obinutuzumab Achieves 76% Response Rate in Active Lupus
303 patients with active SLE (excluding severe lupus nephritis) received obinutuzumab 1,000mg IV or placebo plus standard therapy. The 23.1 percentage point difference in SRI-4 response at week 52 was highly significant (P<0.001): 76.7% versus 53.5%.
DORIS remission rates: 35.1% versus 13.8%. Successful glucocorticoid taper: 80.0% versus 54.1%. The effect size substantially exceeds both belimumab and anifrolumab in their respective pivotal trials.
This represents a major advance for moderate-to-severe SLE management, offering an alternative to continuous immunosuppression.
5. MajesTEC-3: Bispecific Antibody Combination Transforms Relapsed Myeloma Outcomes
587 patients with relapsed/refractory MM after ≥1 prior line received teclistamab + daratumumab versus physician's choice daratumumab-based triplets. Median PFS was not yet reached in the combination arm versus 18.1 months with standard therapy (HR 0.17; P<0.001).
36-month progression-free survival: 83.4%. Complete response or better: 81.8% versus 32.1%. MRD negativity: 58.4% versus 17.1%.
The FDA approved this combination March 5, 2026. This bispecific antibody approach is reshaping myeloma treatment paradigms.
CLINICAL PEARLS THAT MATTER
CD19 CAR T-Cell Therapy Achieves Complete Response in Multirefractory Autoimmune Hemolytic Anemia— 11 patients with multirefractory AIHA (failed ≥3 prior therapies) received single-infusion CD19 CAR T-cell therapy; all achieved complete response with drug-free remission lasting median 11.5 months. NEJM 2026
Antibiotic De-escalation at Day 4 Doesn't Increase Mortality in Sepsis — Target trial emulation across 67 Michigan hospitals (36,924 patients) showed de-escalation of anti-MRSA/anti-pseudomonal coverage at day 4 did not increase 90-day mortality (OR 1.00 and 0.98); de-escalation rates varied 2-fold across hospitals (27%–62%), revealing significant stewardship gaps. JAMA Internal Medicine 2026
90% of Statin-Related Muscle Symptoms Are Nocebo Effect — SAMSON trial crossover design showed mean symptom scores of 16.3 with statin vs 15.4 with placebo vs 8.0 with no treatment (P=0.39), suggesting most patients who discontinued statins for myalgia can successfully restart with proper counseling. SAMSON Trial - JACC
CDC Lowers Pneumococcal Vaccination Age to 50 Years — ACIP updated routine PCV recommendation from 65 to 50 years; PCV21 now covers ~84% of IPD cases in adults ≥50 versus 52% for PCV20, with three regimen options now available. CDC Pneumococcal Guidelines
MONDAY MORNING ROUNDS: 5 KEY DISCUSSION POINTS
RSV vaccine demonstrated 83.3% effectiveness against hospitalization in 131,379 adults ≥60 years—first large pragmatic RCT with hard hospitalization endpoints.
Finerenone provided 25% greater UACR reduction beyond RAAS blockade in T1D nephropathy—first evidence-based add-on therapy for this population.
First-line osimertinib plus chemotherapy extended OS to 47.5 months versus 37.6 months with osimertinib alone (HR 0.77) in EGFR-mutated NSCLC, establishing combination as new standard despite 70% grade 3+ adverse events.
Obinutuzumab achieved 76.7% SRI-4 response versus 53.5% placebo in active SLE, with 35.1% DORIS remission and 80% successful steroid taper—exceeding effect sizes of belimumab and anifrolumab.
Teclistamab plus daratumumab produced 83.4% 36-month PFS in relapsed/refractory myeloma with median PFS not reached versus 18.1 months with standard triplets (HR 0.17).
ESSENTIAL READING
Infectious Disease
Nephrology
Oncology
Rheumatology
Hematology
Cardiovascular Medicine
Preventive Medicine
The content provided in The Rounds Report is for educational and informational purposes only and does not constitute medical advice, diagnosis, treatment recommendations, or professional medical guidance. This newsletter presents summaries and analysis of published medical research and should not be used as a substitute for professional medical judgment, clinical decision-making, or consultation with qualified healthcare providers. Always consult with appropriate medical professionals and refer to original research sources before making any clinical decisions. The Rounds Report does not establish a doctor-patient relationship and readers should not rely on this content for patient care decisions.
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