Page 1454 - Hematology_ Basic Principles and Practice ( PDFDrive )

1294 Part VII Hematologic Malignancies

TABLE Studies of Rituximab Maintenance Therapy in Indolent complication of hair loss. Choice to initiate therapy was associated
80.9 Lymphomas with FLIPI, stage, and grade but FLIPI was not associated with
decision to use a specific treatment approach. In the Lymphocare
Trial Disease Setting Diseases Included Previous Therapy study, significant regional and center differences are observed and
st
ECOG 37 1 line Follicular CVP strongly suggest that physician preference is the predominant factor
Small lymphocytic that drives initial therapy. For example, initial “watch and wait” was
used in 31% of patients in the Northeast, but in 13% of patients in
st
SAKK 38 1 line Follicular Rituximab the Southeast, whereas fludarabine-based chemoimmunotherapy was
Relapsed/refractory Mantle cell
used in 18% of patients in the Southwest and in only 3% of patients
EORTC 39 Relapsed/refractory Follicular CHOP vs R-CHOP in the Northeast.
GLSG 40 Relapsed/refractory Follicular FCM vs. R-FCM
Mantle cell
LYM-5 41 Relapsed/refractory Follicular Rituximab Alkylating Agents
Small lymphocytic
The alkylating agents, chlorambucil and cyclophosphamide, with or
CHOP, Cyclophosphamide, adriamycin, vincristine, prednisone; without prednisone and CVP or CHOP, and other alkylator-based
CVP, cyclophosphamide, vincristine, prednisone; FCM, fludarabine, combination chemotherapy regimens have been the standard of
cyclophosphamide, mitoxantrone; R-CHOP, rituximab plus CHOP;
R-FCM, rituximab plus FCM. therapy for decades. Single-agent alkylators at different doses and
schedules produce overall response (OR) rates of 50% to 75% in
FL. 46,47 Comparable response rates, but higher CR rates with longer
approaches such as SCT is a confusing one for the newly diagnosed progression-free survival (PFS) are seen with CVP compared with
patient (as well as for the physician) and considerable consultation chlorambucil, but have no survival advantage. 48,49 The addition of
time is required to review available treatment approaches. Staging of anthracyclines has not improved the response rate or duration of the
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response in FL is by the revised response criteria. Depending on the response, 50,51 but its use may be associated with a lower risk of histo-
treatment approach used, restaging after two to three cycles of therapy logic transformation. 25,52 This finding has yet to be confirmed, par-
can be useful to ensure responsiveness, and the patient is then fully ticularly in the era of chemoimmunotherapy.
restaged after completion of therapy. Whereas curative approaches are
being sought in aggressive lymphomas, the failure to achieve complete
remission (CR) or complete eradication of disease does not have the Purine Analogues
same implication in FL as in aggressive lymphomas and depending
upon the goal of therapy a partial remission (PR) may be a sufficient The purine analogues have been studied extensively in various types
response to alleviate symptoms. The more commonly used regimens of indolent lymphoma. Fludarabine monotherapy produces response
in indolent lymphomas are shown in Table 80.9. 32–41 rates of 65% to 84%, with 37% to 47% CR in previously untreated
53
In the absence of a clear standard of care with curative potential, patients with FL. In a randomized trial of 381 previously untreated
optimal first-line treatment remains enrolment in randomized clinical indolent lymphoma patients CR rates were higher with fludarabine
42
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trials wherever possible. In the National Lymphocare study, aca- than CVP. Fludarabine combinations result in increased response
demic sites are more likely than community sites to treat patients on rates, with 89% CR rate in an Eastern Cooperative Oncology Group
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clinical trials (12% versus 4%), but it is lamentable that only 6% of (ECOG) trial combining fludarabine and cyclophosphamide, while
patients were enrolled in clinical trials. For patients who are not fludarabine and mitoxantrone (FM), produced a 91% overall response
eligible for or who refuse entry into clinical trials, there is data rate (ORR), 43% CR and 2-year disease-free survival (DFS) of
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demonstrating higher response rates and longer duration of responses, 63%. A higher CR rate was seen with FM (68%) compared with
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and perhaps improved survival with chemoimmunotherapy. Many CHOP (42%) in a randomized trial. The use of alkylator-based
investigators favor alkylator over fludarabine-based regimens for FL, regimens or purine analog–based regimens appears to vary geographi-
based upon concerns regarding the ability to obtain stem cells for cally, suggesting personal preference for the use of regimens in which
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later use for autologous SCT (ASCT) in fludarabine-treated patients. the clinician has experience, rather than alterations of practice based
It is suggested that more aggressive first-line therapy should be offered on the results of the published studies.
to patients who progress within 1 year of presentation, since these
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patients have a worse outcome. Older adult patients or those with
poor performance status may remain candidates for single-agent Bendamustine
chlorambucil, although this is given most often in combination with
rituximab. Single-agent rituximab therapy is appropriate for patients Bendamustine is a potent alkylating agent that has been demonstrated
who choose to avoid chemotherapy and is a reasonable treatment to have substantial efficacy in NHL patients, including those with
choice based upon the results of clinical trials of standard or prolonged FL. Bendamustine is highly effective in rituximab-refractory FL and
induction with or without maintenance therapy with rituximab. in patients whose disease is refractory to other alkylating agents. It
Although data suggest a survival advantage with the use of interferon has also demonstrated considerable efficacy in previously untreated
(IFN)-α in combination with chemotherapy, this is associated with FL, both alone and in combination with rituximab or other chemo-
a significant side effect profile and this agent is now rarely used. therapeutic agents. 58,59 Increased understanding of the mechanisms
Optimal results are seen when radioimmunoconjugates are used of action of bendamustine and the efficacy of bendamustine in
earlier in the disease course. On the basis of results showing no benefit combination with rituximab in newly diagnosed or relapsed/refractory
for ASCT, there is no indication for the use of high dose therapy and FL 44,45,58 has led to investigation of other combinations. Ongoing
SCT in first remission in FL unless as part of a clinical trial. studies are examining bendamustine with other agents.
Chemoimmunotherapy is now the treatment of choice for FL. No
randomized trials demonstrate a benefit for the addition of anthra-
cyclines, but cyclophosphamide, adriamycin, vincristine, prednisone, Biologic Therapy
and rituximab (R-CHOP) is heavily favored over cyclophosphamide,
vincristine, prednisone, and rituximab (CVP-R) or fludarabine-based IFN-α is approved by the Food and Drug Administration (FDA) for
regimens. Following demonstration of improved outcome using the treatment of advanced stage FL in combination with anthracycline-
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bendamustine plus rituximab (BR) compared with R-CHOP or based chemotherapy, based upon improved survival in clinical
45
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to fludarabine plus rituximab, the use of BR has greatly increased. trials, 21,60,61 and meta-analysis of phase III trial data. IFN-α was
BR also has improved tolerability and can be given without the more widely used in Europe than the United States, where it is felt