Transformed lymphoma: what should I do now?

Abstract

Although the majority of indolent lymphomas (focusing on follicular lymphoma [FL]) have a prolonged waxing and waning course, a portion of patients experience histologic transformation (HT) to either diffuse large B-cell lymphoma or a higher-grade morphology, often with acquisition of MYC and BCL2 and/or BCL6 rearrangements (high-grade B-cell lymphoma–double-hit lymphoma/triple-hit lymphoma). The overall incidence of HT and transformed follicular lymphoma (tFL) may be declining, but outcomes remain inferior to those in simple indolent lymphoma progression. Recent data suggest that the majority of HT cases occur in higher-risk patients with FL, and they occur early after initial chemoimmunotherapy, comprising the majority of patients with progression of disease within 24 months. This latter point emphasizes the need for a sufficient biopsy at relapse in FL. Treatment options depend on the prior therapy for the indolent component as well as the histology at relapse, but they generally follow several principles discussed in this article. Anthracycline-naïve patients have the best outcomes if there is HT, and responses to R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) are similar to those of patients with de novo diffuse large B-cell lymphoma. Patients with anthracycline exposure prior to transformation have the best outcomes with salvage chemotherapy and a consolidative autologous stem cell transplant. However, a major challenge is the management of patients with tFL who experience relapse early after bendamustine-based treatment, in whom the role of consolidative transplant after anthracycline-based treatment is unclear. In the past several years, cellular therapy has emerged as an important tool for some but not all patients with tFL. This review focuses on the nuances of managing tFL.

Lenalidomide in combination with R-CHOP produces high response rates and progression-free survival in new, untreated diffuse large B-cell lymphoma transformed from follicular lymphoma: results from the Phase 2 MC078E study

“…These results suggest poor prognosis and need to improve frontline treatment in these patients. The optimal treatment of these patients with intensive therapy and consolidative autologous stem cell transplant (ASCT) has not been determined but has been recommended [33]. Prior rituximab exposure for indolent lymphoma decreases the risk of transformation but is also associated with inferior survival posttransformation [21,30].…”

Prospects in the management of patients with follicular lymphoma beyond first-line therapy

“…Cellular therapy is an important emerging option for patients with histological transformation but unmet needs remain. 5 If histological transformation is ruled out, several options should be considered. Standard options such as obinutuzumab-bendamustine and anti-CD20-lenalidomide combinations are often utilized, and their efficacy in POD24 patients has been demonstrated.…”

“…The use of positron emission tomography/computed tomography to guide the site of biopsy in the nodal area with the highest glucose uptake is recommended. The detailed management of transformed FL has been recently reviewed 5 and is beyond the scope of this paper.…”

Follicular lymphoma: updates for pathologists

“…Some cases follow a chronic relapsing course. A subset progresses rapidly and transforms to aggressive lymphomas such as diffuse large B-cell lymphomas, double-hit large B-cell lymphomas, and lymphoblastic leukemia/lymphoma [ 17 ].…”