DA-EPOCH-R Has Comparable Outcomes in De Novo and Transformed Diffuse Large B Cell Lymphoma

Introduction

It is increasingly recognized that transformed (T) diffuse large B cell lymphoma (DLBCL) is a clinically and biologically distinct entity from de novo DLBCL. Dose escalated etoposide, doxorubicin, vincristine, cyclophosphamide and prednisone with rituximab (DA-EPOCH-R) is effective in aggressive large B cell lymphomas including de novo DLBCL, Burkitt lymphoma, high grade B cell lymphoma with BCL2-Myc rearrangement and primary mediastinal B cell lymphoma. However, outcomes of transformed DLBCL (T-DLBCL) treated with DA-EPOCH-R are not well-studied. Here, we describe our experience with T-DLBCL after treatment with DA-EPOCH-R.

Methods

All adult patients with DLBCL diagnosed and treated with DA-EPOCH-R at Medstar Washington Hospital Center from January 2000 to November 2018 were included in this retrospective study. Data was collected from review of electronic medical records. All transformations were biopsy-proven. T-DLBCL was defined as either biopsy-confirmed DLBCL with background of indolent lymphoma (concurrently transformed (CT) DLBCL) or sequential development of DLBCL in a case of known indolent lymphoma (sequentially transformed, (ST) DLBCL). Patient characteristics including age, sex, race were recorded. Stage, extranodal disease, international prognostic index (IPI) of DLBCL were recorded. For patients with CT and ST DLBCL, histology and prior treatment of indolent lymphoma were recorded. Study objectives were to assess response rates, progression free survival (PFS) and overall survival (OS) for de novo DLBCL, CT-DLBCL and ST-DLBCL treated with DA-EPOCH-R. Fisher’s exact test was used to compare categorical variables between the groups. Kaplan-Meier method was used to calculate survival curves. Log rank test was used to compare survival between de novo DLBCL, CT-DLBCL and ST-DLBCL.

Results

Of 183 DLBCL patients treated during the study period, 34 had T-DLBCL (17 CT-DLBCL and 17 ST-DLBCL). Total 91 received DA-EPOCH-R (25 transformed, 66 de novo) and were included in our study. Median age was 56 (23-84). Sixty percent patients were males and 42% were white. Out of 25 Tx DLBCL, 11 had CT-DLBCL and 14 had ST-DLBCL. Patients with T-DLBCL (CT and ST) had higher odds of being white, having advanced stage, extra-nodal disease and high IPI. [OR: 2.6 (CI₉₅1.7-6), 4.1 (CI₉₅1.6-10), 2.8 (CI₉₅ 2.8 (1.8-7) and 2.7 (CI₉₅1.2-6), respectively. P <0.001]. Cell of origin, BCL2 and BCL6 expression was not available for all DLBCL patients. Follicular lymphoma was the most common underlying indolent lymphoma (13), followed by chronic lymphocytic leukemia (5), marginal zone lymphoma (3), low grade non-Hodgkin lymphoma not otherwise specified (3) and lymphoplasmacytic lymphoma (1). Seven of T-DLBCL had received prior rituximab and 2 had received prior anthracycline. For ST-DLBCL patients, median time to transformation was 2.25 years (0.3-15).

There was no significant difference in ORR (85%, 86%, 91%) and CR (82%, 84%, 89%) of DA-EPOCH-R treated CT, ST and de novo DLBCL, respectively. Median follow up was 5 years. Median PFS and OS for CT and de novo DLBCL were not reached. ST DLBCL had median PFS and OS of 21 years and 37 years, respectively. There was no significant difference between 2-year PFS and OS of CT, ST and de novo DLBCL treated with DA-R-EPOCH. (Table 1).

Conclusion

T-DLBCL is more likely to have aggressive features such as advance stage, extra nodal disease and high IPI. Despite this, DA-EPOCH-R treated T-DLBCL has outcomes comparable to de novo DLBCL. Large, prospective studies are needed to examine efficacy of DA-EPOCH-R in T-DLBCL.