Diffuse Large B-Cell Lymphoma (DLBCL), Frontline & Relapsed Sequencing

Evidence-based treatment sequencing pathway for newly diagnosed diffuse large B-cell lymphoma, integrating frontline polatuzumab vedotin plus R-CHP versus R-CHOP, followed by CD19-directed CAR-T cell therapy or bispecific antibodies for relapsed/refractory disease.

Frontline systemic therapy selection based on International Prognostic Index (IPI) and CD20 status

• Intermediate-to-high risk DLBCL frontline pathway → Polatuzumab vedotin + R-CHP (rituximab, cyclophosphamide, doxorubicin, prednisone)
• Standard R-CHOP frontline selection → R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone)

1L: Polatuzumab vedotin + R-CHP (rituximab, cyclophosphamide, doxorubicin, prednisone)

Preferred frontline standard of care for intermediate-to-high risk DLBCL (IPI 2-5), replacing vincristine with the anti-CD79b antibody-drug conjugate polatuzumab (POLARIX).

• Disease progression or relapse → Disease progression or relapsed/refractory DLBCL evaluation

1L: R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone)

Foundational frontline chemoimmunotherapy standard for low-risk DLBCL or patients where pola-R-CHP is not selected.

• Disease progression or relapse → Disease progression or relapsed/refractory DLBCL evaluation

Disease progression or relapsed/refractory DLBCL evaluation

• Primary refractory or early relapse (≤12 months) → CD19-directed CAR-T cell therapy (axicabtagene ciloleucel / lisocabtagene maraleucel)
• Late relapse — platinum salvage and transplant evaluation → Platinum-based salvage chemotherapy (R-ICE / R-DHAP) ± autologous transplant

2L: CD19-directed CAR-T cell therapy (axicabtagene ciloleucel / lisocabtagene maraleucel)

Category-1 second-line standard for primary refractory disease or relapse ≤12 months after frontline chemoimmunotherapy, superior to salvage chemotherapy + transplant (ZUMA-7 for axi-cel; TRANSFORM for liso-cel).

• Subsequent progression (≥3rd line) → Bispecific T-cell engagers (glofitamab / epcoritamab) or third-line CD19 CAR-T

2L: Platinum-based salvage chemotherapy (R-ICE / R-DHAP) ± autologous transplant

Traditional chemoimmunotherapy salvage followed by autologous stem cell transplantation for transplant-eligible responders, chiefly for late relapse (>12 months) chemosensitive disease.

• Subsequent progression (≥3rd line) → Bispecific T-cell engagers (glofitamab / epcoritamab) or third-line CD19 CAR-T

3L+: Bispecific T-cell engagers (glofitamab / epcoritamab) or third-line CD19 CAR-T

For disease progressing after ≥2 prior lines: CD20×CD3 bispecific antibodies — glofitamab (NP30179) or epcoritamab (EPCORE NHL-1) — or CD19-directed CAR-T (axi-cel, ZUMA-1; liso-cel, TRANSCEND) in patients not previously treated with cellular therapy.

• Subsequent progression → Clinical trial referral / palliative supportive care

3L+: Clinical trial referral / palliative supportive care

Evaluation for novel clinical trials or supportive management in multi-refractory disease.