For elderly patients (e.g., age 79) with diffuse large B-cell lymphoma, clinicians are avoiding CNS prophylaxis. Retrospective data suggests current methods lack benefit, and the risk of harm from intrathecal or high-dose methotrexate outweighs the unproven advantage, especially given the patient's age and potential frailty.
The traditional ABC/GCB classification for DLBCL is flawed. Single-cell sequencing reveals that tumors classified as one type via bulk analysis contain malignant cells of the other subtype. This underlying heterogeneity explains why the distinction is an imperfect predictor and will be replaced by more sophisticated biomarkers like T-cell exhaustion signatures.
Due to a 20% misclassification rate with the Hans algorithm for determining cell of origin, clinicians use an IPI score of 2 or greater as the primary criterion for selecting Polatuzumab-R-CHOP. This avoids potentially giving 1 in 5 patients the wrong therapy based on an imperfect biomarker.
The landmark TRIANGLE trial has redefined frontline therapy for younger, fit mantle cell lymphoma patients. Adding a BTK inhibitor to induction and maintenance provides outcomes superimposable to those including an autologous stem cell transplant. This allows clinicians to omit the transplant, sparing patients significant toxicity without compromising efficacy.
Experts view R-mini-CHOP, the standard for older/unfit DLBCL patients, as a poor benchmark that urgently needs to be replaced. Promising chemo-free or chemo-light regimens, like the R-Polo-Glofitamab combination, are seen as the future, aiming to improve outcomes in this vulnerable population without harsh toxicities.
In the IN-MIND trial for relapsed follicular lymphoma, the tafasitamab-lenalidomide-rituximab arm had zero cases of histologic transformation to a more aggressive lymphoma. This contrasts with nine cases in the control arm, suggesting the CD19-targeting antibody may eradicate precursor cells responsible for this dreaded complication.
When choosing between novel combinations in relapsed follicular lymphoma, a logical strategy is to use tafasitamab-lenalidomide-rituximab (Tafa-R2) first. After progression, single-agent epcoritamab remains highly effective. The reverse is not true, as tafasitamab monotherapy would not be effective after epcoritamab-R2 failure, making the initial choice critical.
The FRONT-MIND trial's positive result for Tafa-Len-R-CHOP must be contextualized. A key eligibility criterion was a diagnosis-to-treatment interval under 28 days. This selected for patients with rapidly progressing, aggressive disease, creating a higher-risk population than in other trials and likely explaining the R-CHOP arm's weaker performance.
The argument against using certain frontline therapies for fear of compromising future CAR-T eligibility is tempered by a stark reality: only 5% of eligible US patients actually receive CAR-T. This logistical and access bottleneck means that optimizing immediate, available treatments is paramount for the vast majority of patients.
Effective management of Loncastuximab Teserine (Lanca-T) requires a hands-on, internist-like approach. Clinicians must perform physical exams to detect trace pretibial edema and proactively start spironolactone at the earliest sign. This prevents progression to severe fluid retention, allowing patients to stay on this effective therapy longer.
The ECHO trial for older mantle cell lymphoma patients presents a clinical dilemma. Adding acalabrutinib to BR chemoimmunotherapy improved progression-free survival (PFS) but not overall survival (OS). This was because the reduction in lymphoma deaths was offset by an increase in fatal infections, creating a difficult risk-benefit discussion.