Treatment of histologic transformation of follicular lymphoma in adults

CAR-T: chimeric antigen receptor T cell; CNS: central nervous system; CR: complete response; CT: computed tomography; DLBCL: diffuse large B cell lymphoma; ECOG: Eastern Cooperative Oncology Group; EPOCH-R: etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab; FL: follicular lymphoma; HCT: hematopoietic cell transplantation; HT: histologic transformation; IPI: international prognostic index; LDH: lactate dehydrogenase; O-CHOP: cyclophosphamide, doxorubicin, vincristine, and prednisone plus obinutuzumab; PET: positron emission tomography; R-CHOP: cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab; R-ICE: rituximab, ifosfamide, carboplatin, and etoposide; R-pola-CHP: rituximab, polatuzumab vedotin, cyclophosphamide, doxorubicin, and prednisone; RT: radiation therapy.

* Have a low threshold to biopsy at the time of disease progression to confirm relapse and evaluate for HT. Signs or symptoms that suggest HT include the rapid progression of lymphadenopathy, infiltration of uncommon extranodal sites (excluding the bone marrow), development of systemic symptoms (eg, fever, weight loss, night sweats), elevated serum LDH, and/or hypercalcemia. Imaging with a combined PET/CT scan can be used to target biopsy at a lymph node with the highest activity on PET.

¶ For most patients with advanced-stage disease without prior exposure to R-CHOP, we suggest 6 cycles of either R-CHOP or R-pola-CHP. R-pola-CHP is preferred for those with an IPI ≥2. To calculate the IPI, one point is allocated for each of the following: age >60, serum LDH above normal, ECOG performance status ≥2, Ann Arbor stage III or IV, and >1 site of extranodal disease. Patients with double-hit HT (those with c-MYC translocation plus gene rearrangement of BCL-2, BCL-6, or both) should be encouraged to enroll on a clinical trial. For those with double-hit HT treated off study, we favor dose-adjusted EPOCH-R rather than R-CHOP or R-pola-CHP.

Δ CAR-T cell therapy is an option for those with HT resembling DLBCL who have received 2 or more lines of systemic therapy (for indolent or transformed disease), have disease that is refractory to first-line chemoimmunotherapy, or relapse within 12 months of first-line chemoimmunotherapy. Patients with exposure to multiple lines of systemic therapy are also candidates for targeted therapies, including epcoritamab, glofitamab, tafasitamab plus lenalidomide, loncastuximab tesirine, and selinexor. A choice among these is individualized. Palliative care alone is a reasonable alternative to these therapies in patients with refractory disease after multiple lines of systemic therapy.