Front-line Polatuzumab Vedotin, Rituximab and Lenalidomide (Pola-R2) achieves deep responses and MRD negativity in profoundly frail elderly patients with diffuse large B-cell lymphoma
Materials and Methods/Case Presentation/Objective: From a cohort of 26 DLBCL patients treated with Pola-R2 at Northwell Health (2021-2024), all deemed ineligible for miniR-CHOP.12 patients were analyzed who received Pola-R2 as first-line therapy. Polatuzumab vedotin (1.8 mg/kg) was administered every 21 days with standard rituximab and lenalidomide 10 mg PO days 1-7. Response was assessed by PET/CT per Lugano criteria. Minimal residual disease (MRD) was assessed by clonoSEQ (Adaptive Biotechnologies) immunoglobulin gene rearrangement sequencing in patients with detectable baseline clonality. ECOG performance status and living situation were documented at baseline and best on-treatment assessment.
Results/Description/Main Outcome Measure(s):
Their median age was 83 years (range 71-92), with 10 (83%) aged ≥80. Median Charlson Comorbidity Index was 8. Eight patients (67%) had baseline ECOG ≥3, including 5 (42%) with ECOG 4. Five patients (42%) resided in nursing homes or rehabilitation facilities at treatment initiation. Cell of origin was non-GCB in 9 (75%).
Among 10 evaluable first-line patients, 9 (90%) achieved CR and 1 (10%) had stable disease, for an ORR of 90%. Baseline clonality was detected in 7 of 12 first-line patients (58%), enabling MRD tracking by clonoSEQ. Among 6 first-line patients with post-treatment MRD assessment, 5 (83%) achieved MRD negativity. Across the full cohort of 26 patients, 10 of 11 CR patients (91%) with trackable clonality achieved MRD negativity, confirming deep molecular responses. MRD negativity was more frequent in non-GCB (9/10, 90%) than GCB (1/5, 20%) patients, consistent with lenalidomide's known preferential activity in the non-GCB subtype.
Ten of 12 first-line patients (83%) demonstrated ECOG improvement, with a median gain of 2 points. Three patients transitioned from institutional care to home. At median follow-up of 8.2 months, no first-line patient experienced relapse or death. The regimen was well tolerated with no treatment-related deaths.
Conclusion(s).: Front-line Pola-R2 achieved a 90% CR rate with 83% MRD negativity in a profoundly frail elderly DLBCL population, substantially exceeding historical R-miniCHOP benchmarks in a considerably more vulnerable cohort. The molecular depth of response, accompanying functional improvement, and absence of relapse in first-line patients support Pola-R2 as a promising chemotherapy-free first-line option for patients previously considered candidates for palliative care alone.
Trademarked Items:
References:
