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1628 Part XI: Malignant Lymphoid Diseases Chapter 98: Diffuse Large B-Cell Lymphoma and Related Diseases 1629

TABLE 98–3. Treatment of Limited-Stage Aggressive (OS) curves overlapped at 9 years. The early treatment advantage of
CHOP plus IFRT disappeared as a result of lymphoma recurrence
Lymphoma
between 5 and 10 years after therapy. 42
5-Year OS In an Eastern Cooperative Oncology Group (ECOG) trial involv-
Patient Number of (p value) ing 399 patients with bulky stage I (mediastinal or retroperitoneal mass,
Population Patients Treatment (%) Ref. or a mass >10 cm), stage IE, stage II, or stage IIE disease, patients who
Stages I and 401 8 cycles 72 41, 42 achieved complete remission (CR) after CHOP chemotherapy were ran-
II, nonbulky CHOP domized to observation or 30 Gy involved-field radiation. All patients
43
vs. with partial remission received 40 Gy to the involved field and radia-
tion to the contiguous noninvolved regions. Among 172 CR patients,
3 cycles 82 the 6-year disease-free survival (DFS) was 73 percent for low-dose
CHOP + IFRT (p = 0.05)
involved-field radiation versus 56 percent for CHOP followed by obser-
Bulky stages 399 8 cycles 73* 43 vation only (p = 0.05) without a survival difference between the two
I, IE, II, and CHOP arms. After 6 years failure-free survival was 63 percent in patients in
IIE partial remission (PR), and conversion to CR with radiation therapy did
vs. not influence outcome. For patients in CR after eight cycles of CHOP,
8 cycles 87 low-dose involved-field radiation prolonged DFS and provided local
CHOP + IFRT (p = 0.24) control, but did not influence survival.
In a Group d’Etude des Lymphomes de l’Adulte (GELA) study, 576
Age >60 576 4 cycles 72 44 patients older than age 60 years with stages I and II disease and an IPI
years, IPI O CHOP
score of 0 were randomized to four cycles of CHOP with or without
vs. involved-field radiation (40 Gy). The 5-year event-free survival (EFS)
44
4 cycles 68 was 61 percent for patients treated with CHOP compared to 64 per-
CHOP + IFRT (p = 0.5) cent for patients treated with CHOP plus involved-field radiation, and
the OS was 72 and 68 percent, respectively. In another GELA study,
Age <61 647 ACVBP 90 45
years, local- vs. 647 patients younger than age 61 years with low-risk localized aggres-
ized stages I sive lymphoma were randomized to three cycles of CHOP followed by
and II, IPI O 30 to 40 Gy of involved-field radiation or doxorubicin (Adriamycin),
cyclophosphamide, vindesine, bleomycin, and prednisone (ACVBP)
3 cycles 87 chemotherapy followed by consolidation chemotherapy with metho-
CHOP + IFRT (p <0.001)
45
trexate, ifosfamide, etoposide, and cytarabine. The EFS (82 percent vs.
Stages I and 60 R-CHOP + 92 46 74 percent, p = 0.001) and OS (90 percent vs. 87 percent, p <0.001) were
II with IPI >O IFRT significantly better for patients given intensive chemotherapy alone
CHOP, cyclophosphamide, doxorubicin, vincristine, and prednisone; compared to patients given CHOP chemotherapy plus radiation ther-
IFRT, involved-field radiation therapy; IPI, international prognostic apy. The ACVBP regimen cannot be given in the United States, however,
index; OS, overall survival; R-CHOP, rituximab, cyclophosphamide, because vindesine is not available.
doxorubicin, vincristine, and prednisone. These studies were conducted before the incorporation of rituximab
*OS for 172 complete remission patients randomized to observation into frontline regimens for DLBCL. Subsequently, in a phase II study, 60
versus involved-field radiation therapy. patients older than age 60 years with at least one adverse risk factor as
defined by the IPI (but excluding bulky stage II disease) received rituximab
46
and CHOP (R-CHOP), followed by 40 to 46 Gy involved-field radiation.
PFS was 95 percent at 2 years and 88 percent at 4 years, and OS was 95
only 50 percent, and in stage II disease was approximately 20 percent. percent at 2 years and 92 percent at 4 years. PFS and OS for historical con-
Combining chemotherapy with radiation therapy improved the control trols not treated with rituximab were 78 percent and 88 percent at 4 years,
of local disease and resulted in a lower rate of delayed dissemination. 35–40 respectively. Additional, retrospective analyses suggest a role for radio-
The role of chemotherapy alone, and cyclophosphamide, doxorubicin, therapy in unselected DLBCL patients (including limited stage disease)
47
vincristine, and prednisone (CHOP) in particular, has been studied in treated with R-CHOP, and in subsets age 61 to 80 years with bulky disease
several randomized trials (Table 98–3). (7.5 cm or greater). 48
A Southwest Oncology Group study randomly assigned 401 Although the data available are not clearcut, at this time either
patients with stage I and nonbulky stage II disease to receive either eight three cycles of R-CHOP followed by 40 to 46 Gy of involved-field radi-
cycles of CHOP chemotherapy or three cycles of CHOP plus involved- ation or six cycles of R-CHOP without radiotherapy represent standard
field radiotherapy (IFRT). The 5-year overall and progression-free therapeutic options.
41
survival (PFS) rates of the patients treated with the short-course, com-
bined modality approach were significantly better (82 percent and ADVANCED STAGE DIFFUSE LARGE B-CELL
72 percent, respectively, p = 0.02) than outcomes among patients treated
with chemotherapy alone (77 percent and 64 percent, respectively, LYMPHOMA
p = 0.03). Cardiac and hematologic toxicity was greater in patients Combination chemotherapy (mechlorethamine, vincristine, procarba-
treated with eight cycles of CHOP without radiation therapy. A subset zine, prednisone [MOPP]) proved so successful for treatment of Hodg-
analysis using modified IPI criteria showed that patients with poor risk kin lymphoma that similar regimens were soon explored for treatment
factors had a worse overall survival. However, with longer followup, fail- of DLBCL, including cyclophosphamide, vincristine, procarbazine,
ure-free survival curves overlapped at 7 years and the overall survival and prednisone (C-MOPP; synonym: COPP) and cyclophosphamide
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Kaushansky_chapter 98_p1625-1640.indd 1628 9/18/15 11:42 PM