Lymphoid cancers of different types and subtypes are known to cluster in families. We hypothesize that there are shared susceptibility factors in families with these heterogenous lymphoid malignancies. Exome sequencing was performed on 100 individuals from 43 lymphoid cancer pedigrees. Variants from 37 families were ranked using the Weights-based vAriant Ranking in Pedigrees (WARP) pipeline. Six affected unrelated probands were used for interpretation only. We detected recurrent variants in the germline lymphoid cancer gene FAM160A1 in 4 (9%) of the 43 families, and variants in other genes involved in lymphoid cancers: NPAT, BCL9, HCLS1 and ID3. Variants in genes including BCL9, LEF1, TLE3, and KLHL12 involved in the WNT/β-catenin pathway were identified, representing a novel observation. Some variants appeared to segregate with specific types of lymphoid cancers; others were shared across different subtypes. Identifying factors predisposing to different types of lymphoid cancers will help understand the etiology of these neoplasms.

Early hemorrhagic death in acute promyelocytic leukemia (APL) remains a major, preventable cause of mortality. Although guidelines recommend empiric all-trans retinoic acid (ATRA) at first suspicion of APL, real-world initiation varies. We conducted a multicenter retrospective cohort study within the TriNetX U.S. Collaborative Network to evaluate the impact of early ATRA initiation. Adults with laboratory-confirmed APL (PML-RARA) presenting to the emergency department (ED) were categorized by ATRA initiation within 24 h (early) versus after 24 h (delayed). The primary outcome was 30-day mortality; secondary outcomes included major hemorrhage, ICU admission, thrombosis, and sepsis. Among 596 patients, 137 (23%) received early ATRA. After 1:1 propensity score matching (n = 137 per group), early ATRA was associated with lower 30-day mortality (10.2% vs 26.2%) and reduced major hemorrhage, while other outcomes did not differ. The absolute mortality risk reduction was 16%, yielding a number-needed-to-treat of seven. Early ED ATRA initiation substantially improved survival in PML-RARA–confirmed APL.

Chemotherapy is the main treatment for diffuse large B-cell lymphoma (DLBCL); yet 30–40% of patients are considered relapsed or refractory (R/R) to initial therapy and have second-line therapy (2 L). There is a need to study real-world outcomes to address the changing treatment landscape for R/R DLBCL patients. This study examined treatment patterns, healthcare utilization and costs, and survival among Medicare R/R DLBCL patients from 2016 to 2022. Study patients (n = 3,191) were an average of 75.7 years old and only 30.6% of patients initiated 3 L. Patients with 3 L incurred higher costs ($15,133 per-patient per-month [PPPM]) than all patients ($9,487 PPPM). Half of patients died within 6.7 months from start of 2 L. Patients with older age and elevated comorbidity burden had significantly shorter survival times within 3 years after 2 L initiation. Our analyses indicate a high disease burden among R/R DLBCL patients, highlighting the need for new treatments.

Lenalidomide (Len) maintenance improves survival after upfront autologous stem cell transplantation (autoHCT) in multiple myeloma (MM), but its role after delayed/salvage autoHCT is less defined. We performed a retrospective study of 163 MM patients who received delayed (n = 102) or salvage (n = 61) autoHCT between 2009 and 2023, followed by Len maintenance. After median follow-up of 50 months, median progression-free survival (PFS) and overall survival (OS) were 23 (95% CI, 20–26) and 62 (95% CI, 50–80) months, respectively. Patients with high-risk cytogenetic abnormalities had inferior outcomes (PFS 8 months; OS 27 months). In multivariable analysis, achieving ≥ complete response post-transplant improved PFS (hazard ratio [HR] 0.49, p = 0.002) and OS (HR 0.44; p = 0.002). Len maintenance ≥5 years was associated with improved PFS (HR 0.19; p < 0.001) and OS (HR 0.15; p = 0.002). Fourteen patients (9%) developed second primary malignancies. In conclusion, extended Len maintenance was associated with prolonged survival after delayed/salvage autoHCT.