Relapsed/refractory DLBCL with confirmed CD20 expression on malignant B-cells, post ≥2 pr...

Детермінований перегляд YAML-сутності з джерельної бази. Клінічний авторитет лишається за вказаними source ID та статусом клінічного sign-off.

ID	`RF-DLBCL-CD20-POS-GLOFITAMAB-CANDIDATE`
Тип	Тривожна ознака
Статус	переглянуто 2026-04-29
Хвороби	`DIS-DLBCL-NOS`
Джерела	`SRC-ESMO-DLBCL-2024` `SRC-NCCN-BCELL-2025`

Походження тривожної ознаки

Визначення	Relapsed/refractory DLBCL with confirmed CD20 expression on malignant B-cells, post ≥2 prior systemic therapies including one anti-CD20 antibody-containing regimen (R-CHOP), CAR-T-ineligible or post-CAR-T failure — candidate for glofitamab (CD20xCD3 2:1 bispecific T-cell engager; intravenous; fixed 12-cycle duration). Pivotal data NP30179 phase 1/2 (Dickinson 2022 NEJM): ORR 52%, CR 39%, mPFS 4.9 mo, mDOR 18.4 mo in 3L+ R/R DLBCL after fixed treatment course. Differentiator vs epcoritamab: fixed-duration (12 cycles ≈ 8.3 mo) vs continuous; IV vs SC; obinutuzumab pre-treatment 7 days before C1D1 reduces CRS. Off-the-shelf alternative to CAR-T. Often considered after epcoritamab failure in BiTE-sequencing strategies, though direct comparative data are lacking.
Клінічний напрям	intensify
Категорія	high-risk-biology

Логіка спрацьовування

{
  "all_of": [
    {
      "any_of": [
        {
          "finding": "cd20_status",
          "value": "positive"
        },
        {
          "finding": "cd20_ihc",
          "value": "positive"
        },
        {
          "finding": "cd20_expression",
          "value": "preserved"
        }
      ]
    },
    {
      "any_of": [
        {
          "comparator": ">=",
          "finding": "prior_lines_count",
          "threshold": 2
        },
        {
          "finding": "post_cart_failure",
          "value": true
        },
        {
          "finding": "post_epcoritamab_failure",
          "value": true
        },
        {
          "finding": "primary_refractory",
          "value": true
        }
      ]
    },
    {
      "any_of": [
        {
          "finding": "cart_ineligible",
          "value": true
        },
        {
          "finding": "cart_ineligibility_reason"
        },
        {
          "red_flag": "RF-DLBCL-CART-INELIGIBLE-POST-2L"
        },
        {
          "red_flag": "RF-CAR-T-INELIGIBLE-AGE-COMORBID"
        },
        {
          "red_flag": "RF-CAR-T-INELIGIBLE-ORGAN"
        },
        {
          "finding": "post_cart_relapse",
          "value": true
        }
      ]
    }
  ],
  "type": "composite_score"
}

Нотатки

Pivotal trial Source SRC-NP30179-DICKINSON-2022 not yet ingested — flagged in commit body for follow-up source-stub chunk; efficacy figures cited inline reflect Dickinson et al. NEJM 2022 387(24):2220-2231 (DOI 10.1056/NEJMoa2206913). Schedule: obinutuzumab 1000 mg IV pre-treatment day -7; step-up C1D8 2.5 mg, C1D15 10 mg, C2D1 30 mg, then 30 mg q3w cycles 2-12 (fixed 12 cycles total). CRS ~63% any grade / 4% G3+ (concentrated cycle 1); ICANS ~8% / ~3% G3+. Tocilizumab + corticosteroid for CRS. Sequencing: glofitamab activity post-CAR-T preserved; post-BiTE (epcoritamab) data emerging. Fixed-duration is operationally simpler than continuous SC dosing for low-resource settings. NOT to be used in CD20-negative escape variants — re-biopsy if late-relapse. STUB — requires clinical co-lead signoff.

Де використовується

Indications

IND-DLBCL-3L-GLOFITAMAB - IND-DLBCL-3L-GLOFITAMAB