Five papers: June 4, 2026

NEJM | IF ~100 | Phase 1–2 open-label, multicenter, nonrandomized trial | N = 189

Sponsor: Taiho Oncology | Lead author: Gail J. Roboz, MD (Weill Cornell Medicine / NewYork-Presbyterian) | Trial registration: NCT04657081 | Peer-review status: Published in print NEJM, Vol. 394, June 4, 2026

The clinical gap: Most adults newly diagnosed with AML cannot tolerate intensive induction chemotherapy — either because of age (≥75 years) or comorbidity. Hypomethylating agents plus venetoclax became standard, but all existing regimens required subcutaneous or intravenous administration on a monthly hospital or clinic schedule.

What ASCERTAIN-V did: The trial evaluated whether an all-oral formulation of decitabine plus cedazuridine (Inqovi, which bypasses first-pass CYP3A4 degradation) combined with oral venetoclax could match IV/SC efficacy without pharmacokinetic interference. Phase 1–2a (n=88) confirmed no drug-drug interaction; Phase 2b (n=101) measured CR rate as primary endpoint.

Key results:

Grade ≥3 AEs: anemia 30%, neutropenia 26%, febrile neutropenia 25%. An adaptive dosing strategy after blast clearance reduced the febrile neutropenia burden in later cycles. 1

The FDA approved this combination on May 13, 2026, before the NEJM publication. 2

Clinical implication: An all-oral regimen with CR/CRi of 63% and early mortality at 3% at 30 days compares favorably with published IV/SC HMA-venetoclax data. For older, frail patients, eliminating monthly infusion visits is both logistically significant and financially meaningful. As Roboz said, "We hope these results point to a future for AML patients where the treatment journey is less disruptive and less burdensome without sacrificing outcomes." 2

Both trials were published June 3, 2026, both led by John H. Stone (Harvard Medical School / Massachusetts General Hospital), and both tested secukinumab (IL-17A inhibitor, Cosentyx; Novartis) against a 52-week sustained-remission endpoint. The outcomes diverged.

Trial: N=381 patients with recently relapsed PMR, randomized 1:1:1 to secukinumab 300 mg, 150 mg, or placebo across 27 countries; all groups received a 24-week prednisone taper. | Registration: NCT05767034 | Presentation: Simultaneously at EULAR 2026

Primary endpoint (sustained remission at week 52): 4

SAEs were numerically similar across arms (13–16%). No new safety signal; fungal infections and UTI were modestly more frequent with secukinumab. Novartis has filed for regulatory approval in the US, EU, and Japan. 5

Clinical implication: PMR has no approved steroid-sparing biologic. Tocilizumab (IL-6 inhibition) has shown consistent benefit in giant cell arteritis (GCA), but only limited PMR data exist. REPLENISH establishes IL-17A inhibition as a viable steroid-sparing strategy, cutting cumulative glucocorticoid exposure by roughly 490 mg annually.

Trial: N=353 patients with new-onset or relapsing GCA, randomized to SEC-300 mg (n=140), SEC-150 mg (n=98), or placebo (n=115); SEC groups received a 26-week GC taper versus a 52-week taper for placebo. | Registration: NCT04930094

Primary endpoint (sustained remission at week 52): 6

The difference of 8.7 percentage points for the 300 mg dose (95% CI −1.3 to 18.8) did not reach statistical significance. The placebo arm used a longer taper, which may have inflated its remission rate relative to a shorter-taper design, but the trial failed its primary endpoint regardless. For context, tocilizumab in the GiACTA trial achieved 56.0% sustained remission versus 14–18% with placebo.

Clinical implication: IL-17A inhibition separates across the two related conditions sharing a shared inflammatory pathway. Tocilizumab remains the only evidence-backed biologic for GCA. The paired publication of REPLENISH (positive) and GCAptAIN (negative) in the same week makes the biological specificity of these pathways practically relevant for rheumatology practice.

NEJM | IF ~100 | Phase 1 safety run-in, Brief Report | N = 2 (sequential case cohort) | Funding: NIAID (CTOT U01-AI163087) | Lead author: Ali Naji, MD, PhD (University of Pennsylvania); co-investigator Robert Montgomery, MD, PhD (NYU Langone) | Registration: NCT06056102 | Peer-review status: Published in print NEJM, June 4, 2026

Background: Approximately 5,000 of the 91,000-plus patients on the US kidney transplant waitlist carry panel-reactive antibody (PRA) levels of ≥99.9% — meaning they are immunologically incompatible with virtually all available donors. Conventional plasmapheresis plus IVIG desensitization can reduce PRA transiently but antibody rebound frequently prevents transplantation.

Approach: Dual-target CAR T-cell therapy (anti-CD19 + anti-BCMA) was used to eliminate both plasma cells and their precursors as sources of preformed anti-HLA antibodies. Both patients underwent lymphodepleting chemotherapy, received the CAR T infusion, then had five sessions of plasmapheresis beginning one month post-infusion, followed by low-dose IVIG. Anti-HLA antibody titers dropped sufficiently to delist unacceptable HLA antigens.

Outcomes: Both patients received kidney transplants. Neither patient showed donor-specific antibody (DSA) rebound post-transplant. No high-grade adverse events occurred; immune reconstitution proceeded as expected. Post-transplant immunosuppression followed a standard protocol (ATG induction, tacrolimus/MMF/prednisone). 78

A separate Brief Report in the same NEJM issue (Schrezenmeier et al., NEJMc2517277) described a third case using a single anti-CD19 CAR T-cell product (KYV-101) alone, which also achieved successful transplantation.

Clinical implication: This is a proof-of-concept, not yet practice-changing at scale. The dual-CAR strategy requires lymphodepletion, CAR T manufacturing, and post-infusion plasmapheresis — a resource-intensive pathway. The absence of DSA rebound is the critical data point: prior desensitization approaches saw early antibody return. If confirmed in a larger cohort, this approach could offer a path to transplantation for a population that currently faces median waitlist times exceeding a decade. As Naji stated, "This is the first demonstration that CAR T cells can be used not only to treat cancer, but also to help patients who previously had no opportunity to receive a compatible donor kidney." 8

JAMA Cardiology | IF ~24 | Randomized controlled trial | N = 206 | Sponsor: Vinnova, Swedish Heart-Lung Foundation | Lead author: Jonatan Fernstad (Karolinska Institutet); Corresponding author: Johan Engdahl, MD (KI, Cardiology) | DOI: 10.1001/jamacardio.2026.1269 | Conflict: Fernstad is founder of Corai Medicinteknik AB (developer of the CORAI device) | Peer-review status: Published JAMA Cardiology, June 3, 2026

Clinical problem: Electrical cardioversion for atrial fibrillation (AF) has a same-day cancellation rate of roughly 20% across published series, with the most common reason being spontaneous reversion to sinus rhythm before the procedure. The patient arrives in SR, the procedure is cancelled, but the visit — and the associated anticoagulation coordination, nursing time, and slot blocking — still consumed resources. Most patients do not actively notify the cardiology team when their rhythm changes at home.

Intervention: The SMARTBEATS trial randomized 206 patients scheduled for elective cardioversion at Danderyd Hospital, Sweden (2022–2025) to twice-daily smartphone PPG recording (CORAI, fingertip camera-based) for 1–2 weeks pre-procedure versus standard care.

Results:

Median patient age was 70 years; 99% of enrolled patients owned a smartphone. In the control group, 3 of the patients who had reverted to sinus rhythm proactively contacted the team to cancel. Most did not. 9

Clinical implication: A 94.7% relative reduction in spontaneous-SR cancellations is operationally relevant. The main limitation is that this was a single-center Swedish trial in a population with 99% smartphone ownership and median age 70 — factors that favor uptake. The conflict of interest from the device developer leading the trial warrants attention in any implementation context. The broader question is whether similar PPG-based pre-procedure monitoring could reduce cancellation burden in other elective cardiac interventions (e.g., ablation). Engdahl noted: "This is important because untreated atrial fibrillation increases the risk of stroke and heart failure" — the monitoring acts on utilization but the downstream stroke-prevention rationale is indirect; the trial was not powered or designed to assess stroke outcomes. 9