Treatment of Large Cell Lymphoma: R-CHOP and Beyond

Andre Goy, MD, MS

The treatment of diffuse large B-cell lymphoma (DLBCL) continues to evolve, as researchers seek to improve upon the current standard of care. At the New Frontiers in the Management of Solid and Liquid Tumors conference held in early November in Hackensack, New Jersey, Andre Goy, MD, MS, chairman and director and chief of the Lymphoma Division at the John Theurer Cancer Center, described treatment approaches for early-stage DLBCL and discussed strategies for enhancing treatment of advanced DLBCL.

Early-Stage DLBCL

In patients with stage I, non-bulky DLBCL, the standard treatment is 3 cycles of R-CHOP (rituximab [Rituxan], cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone) with or without radiotherapy, Goy said. Patients with a negative PET scan after 3 R-CHOP cycles can receive more R-CHOP, whereas a positive PET scan likely indicates the need for radiotherapy. Patients with stage I bulky or extranodal, or stage II non-bulky DLBCL should, in most cases, receive 6 cycles of R-CHOP along with radiation treatment, noted Goy. However, he added that researchers are exploring the possibility of limiting the use of radiation in these patient subgroups.

Patients with stage II bulky DLBCL should be treated with the same approach as patients with advancedstage DLBCL.

Advanced-Stage DLBCL

Goy also discussed several potential strategies to improve upon R-CHOP 21 (R-CHOP treatments administered every 21 days), the current standard of care for advanced DLBCL.

Adjusting the quantity of R-CHOP cycles, such as increasing the number from 6 to 8, does not improve patient outcomes. Neither does increasing the regimen frequency to every 14 days (R-CHOP-14), Goy explained. Post-induction consolidation therapy with high-dose chemotherapy (HDT) and autologous stem cell transplantation (ASCT) also does not improve overall survival (OS) in patients receiving rituximab. Goy noted that while the lack of an OS benefit means HDT/ASCT should not be par t of routine upfront consolidation, researchers are hoping to identify a subpopulation that benefits from this treatment approach.

Continuous infusion with dose-adjusted R-EPOCH (rituximab plus etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin hydrochloride) has been employed as another potential strategy for improving outcomes versus R-CHOP-21; however, Goy cautioned that the data for this treatment are still inconclusive.

One approach that has demonstrated an increased benefit versus R-CHOP-21 is a more intensified induction regimen using R-ACVBP (rituximab plus doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisone). R-ACVBP has demonstrated improved progression-free survival and OS versus R-CHOP. However, it has a worse toxicity profile, including higher rates of febrile neutropenia and transfusion.

Looking Ahead

Patient stratification is key to advancing DLBCL treatment going forward, Goy said. However, current options for identifying patient subsets are limited. Evidence is lacking for use of early interim PET scans to identify patients who require more intense therapies. Additionally, while tremendous progress has been made in understanding the biological heterogeneity of DLBCL, it is still not possible to make treatment decisions based on these advancements.

In terms of novel therapeutics on the horizon, Goy said that there are several clinical trials testing the addition of experimental therapies to R-CHOP. One specific combination that has shown promising results is the addition of the monoclonal antibody epratuzumab to R-CHOP-21. Initial results have indicated that the combination improves event-free survival, and ongoing studies are further evaluating its efficacy.