Conventional CHOEP-R Beats Intensified CHOEP-R in Younger Patients with Aggressive B-Cell NHL

NEW ORLEANS, LA — Treatment with 8 cycles of CHOEP-R (cyclophosphamide, vincristine, doxorubicin, prednisone, etoposide, rituximab)-14 achieved excellent interim results in young, high-risk patients with previously untreated aggressive B-cell lymphoma, while the comparator arm of intensified CHOEP-R-21 followed by autologous stem cell transplant (MegaCHOEP-R) was inferior and had greater toxicity. These results led to the discontinuation of the MegaCHOEP-R arm in the MegaCHOEP Trial of the German High-Grade Non-Hodgkin lymphoma (NHL) Study Group.

At 3 years, event-free survival (EFS), defined as “time from randomization to either disease progression, no CR/CRu at the end of treatment, initiation of salvage therapy, or relapse or death from any cause,” was 71% for conventional CHOEP-R, progression-free survival (PFS) was 76%, and overall survival (OS) was 84%. “These results with conventional therapy are the best 3-year ever reported for this group of patients,” stated Norbert Schmitz, MD, ASKLEPIOS Klink St. Georg, Hamburg, Germany.

When originally initiated in 2002, the study enrolled 363 patients ages 18-60 with an International Prognostic Index (IPI) score 2-3 and stage III or IV aggressive B-cell lymphoma. Patients were randomized to one of 4 arms: a conventional CHOEP regimen (consisting of cyclophosphamide, vincristine, doxorubicin, prednisone, and etoposide) with or without rituximab versus intensified CHOEP (the same drugs administered at the highest possible doses and dose intensity) followed by autologous stem cell transplantation plus or minus rituximab. As data on rituximab accumulated, the arms that did not include rituximab were closed (n = 31) and the study was collapsed to two arms, comparing rituximab added to conventional CHOEP and intensified CHOEP. CHOEP-R-14 was given every 2 weeks while MegaCHOEP-R was administered every 21days.

The interim analysis presented at the 2009 ASH annual meeting focused on 260 patients with CD-20-positive B-cell NHL. Ninety percent of patients had diffuse large B-cell lymphoma; median age was 48 years; age-adjusted IPI score was 2 in 70% and 3 in 30%. About 77% of patients had extranodal involvement. No significant differences in demographics or disease characteristics were seen between the two arms.

More patients were able to receive the planned protocol in the conventional CHOEP-R arm: 86.8% versus 61% for MegaCHOEP-R. Major toxicities included mucositis, diarrhea, and infections, which were significantly more frequent in the MegaCHOEP-R arm of the study. More patients died of lymphoma-associated causes in the intensified arm than in the conventional therapy arm (13 vs 8, respectively).

Patients in the conventional therapy plus rituximab arm had a higher rate of complete response/unconfirmed complete response than those in the MegaCHOEP-R group, at 79.1% versus 72.3%, respectively. Conventional CHOEP-R was superior to MegaCHOEP: 3-year EFS was 71% versus 56.7%, respectively; PFS was 76% versus 64.6%, respectively; and OS was 83.8% versus 75.3%, respectively. “The 3-year OS of 84% with conventional therapy was remarkable,” Dr Schmitz said.

Outcomes

CHOEP-R-14

(n = 91)

MegaCHOEP-R

(n = 94)

CR/CRu, %

79.1

72.3

3-Year EFS, %

71

56.7

PFS, %

76

64.6

OS, %

83.8

75.3

Lymphoma-associated deaths, no

8

13

Received planned protocol, %

86.8

61

CR/CRu indicates complete response/unconfirmed complete response; EFS, event-free survival; PFS, progression-free survival; OS, overall survival.

Comparing data from the chemotherapy-only arms with that from the chemotherapy plus rituximab arms demonstrated a 21% difference in 3-year EFS favoring rituximab. “This was unexpected and confirms the importance of rituximab in this setting.”

During the question-and-answer period, Dr Schmitz acknowledged that this study did not show whether high-dose therapy with autologous stem cell transplant was better than conventional therapy. He said that the German group has abandoned high-dose therapy and autologous stem-cell transplant in this setting. He also said it may be possible to remove etoposide from the regimen, but cautioned that he was not certain of this because of the “unexpectedly good results” with conventional CHOEP-R in this study. ASH Abstract 404.