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1648 Part XI: Malignant Lymphoid Diseases Chapter 99: Follicular Lymphoma 1649

1.00
1.00 Survival after transformation

0.75
Proportion transforming 0.50 Cumulative incidence of transformation Proportion surviving 0.75

0.50

0.25 N = 325 0.25

N = 88

0 2 4 6 810121416182022242628303234 0 2 4 6 8 101214161820222426
Time (years) Time (years)
A B
Figure 99–6. A. Transformation of follicular lymphoma (FL) to an histologic pattern compatible with rapid progression of disease. The line depicts
the cumulative incidence of histologic transformation to a histologic pattern compatible with more rapid progression (e.g., diffuse large B-cell
lymphoma) in 325 patients followed from the date of diagnosis of FL. B. The proportion of patients with FL surviving after transformation to a less-
favorable histologic pattern. The graph shows the survival of the 88 patients from the date of their transformation to aggressive lymphoma. (Repro-
duced with permission from Montoto S, Davies AJ, Matthews J, et al.: Risk and clinical implications of transformation of follicular lymphoma to diffuse large
B-cell lymphoma. J Clin Oncol 25(17):2426–2433, 2007.)

approximately 3 percent (Fig. 99–6A). Clinically, histologic transforma- or IV disease are best monitored with observation alone, particularly
tion is characterized by the sudden explosive growth of a single lymph if their disease is of low volume and if they have multiple coexistent
node site (or extranodal mass). Anthracycline-based chemotherapy medical illnesses. Patients who are symptomatic, have cytopenias, mas-
(e.g., R-CHOP) is the most appropriate therapy for patients experienc- sive splenomegaly, effusions, or bulky adenopathy should be treated
ing transformation, however, most studies indicate that the prognosis with rituximab plus chemotherapy. Several regimens are acceptable
is poor despite aggressive management. Whereas 50 to 65 percent of including BR, R-CVP, and R-CHOP, with the latter regimen being most
patients presenting with de novo diffuse large B-cell lymphoma are appropriate for young patients with aggressive presentations and rapidly
cured with R-CHOP chemotherapy, less than 10 percent of patients with growing bulky adenopathy, B symptoms or for patients with grade 3
diffuse large B-cell lymphoma arising by transformation from FL will FL. The roles of maintenance rituximab and consolidative RIT following
be cured by this regimen (Fig. 99–6B). Most series report median sur- initial induction chemoimmunotherapy of newly diagnosed patients are
vivals of 6 to 20 months for patients undergoing transformation, 29,78–80 contentious. It appears that either rituximab maintenance for 2 years or
although one recent study reports a 50-month median survival, with a single dose of consolidative RIT with Y-ibritumomab tiuxetan can
90
particularly good survival in patients experiencing transformation more prolong initial remission duration and PFS, but neither improves OS.
than 18 months after initial diagnosis of FL. Because of the historically Management of FL following relapse depends on the patient’s initial
81
poor outcome of chemotherapy alone, some authorities advise either treatment and the resultant remission duration. If the first remission
autologous or allogeneic stem cell transplantation following induc- lasts many years, the initial treatment regimen may again be used (except
tion of remission with R-CHOP. A recent multicenter cohort study of for anthracycline-containing regimens). If the initial remission is short,
172 patients with transformed FL concluded that patients undergoing an alternative second-line regimen should be selected from among the
autologous stem cell transplantation had better outcomes than those many available options, including BR, R-CVP, R-CHOP, R-FND (ritux-
treated with rituximab-containing chemotherapy alone. However, imab, fludarabine, mitoxantrone [Novantrone], and dexamethasone),
allogeneic transplantation did not improve outcomes compared with and RIT. In the near future, many additional attractive options will be
rituximab-containing chemotherapy because of high rates of trans- available, including ibrutinib, 83,84 idelalisib, 85,86 ABT-199, 87,88 antibody–
plant-related mortality. 82 drug conjugates, and adoptive immunotherapy with chimeric antigen
89
receptor modified T lymphocytes. 90,91 Patients with a good performance
A PRAGMATIC APPROACH TO THERAPY OF status, who experience very short response durations, should be con-
sidered for autologous or allogeneic stem cell transplantation. Patients
FOLLICULAR LYMPHOMA who undergo histologic transformation should receive R-CHOP and be
There is currently little consensus among lymphoma experts with regard offered the option of stem cell transplantation.
to the optimal management of patients with either frontline or relapsed
FL. Therefore, at this time all patients with FL should be considered COURSE AND PROGNOSIS
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for entry into clinical trials to define the best regimens and to allow
evaluation of the multitude of promising new drugs and antibodies that FL has been considered an indolent but incurable disease for which
are now available. Patients who are ineligible for trials or who decline the median survival of approximately 10 years is minimally affected
enrollment should receive individualized treatment. Patients with local- by medical interventions. This attitude is no longer valid, and survival
ized stage I or II disease may be offered local radiotherapy, observation of FL patients has been progressively increasing over the past 20 years
or chemoimmunotherapy. Elderly patients with asymptomatic, stage III (Fig. 99–7). 92–94 Much of the improvement in survival appears

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