Page 1527 - Hematology_ Basic Principles and Practice ( PDFDrive )

1354 Part VII Hematologic Malignancies

I/II study using concurrent chemotherapy and radiotherapy was higher than in the CHOP-14 arm, with substantially more grade 3
reported. Patients were treated concurrently with radiotherapy and or 4 cytopenias in the VCAP-AMP-VECP arm, which included three
chemotherapy, which included carboplatin, etoposide, ifosfamide, toxic deaths. Because most patients with ATL do not have curable
and dexamethasone. Among the 26 patients reported, the objective disease when treated with these chemotherapy regimens, it is reason-
response rate (ORR) was 81% with 77% CR. The most common able to consider allogeneic stem cell transplantation (aSCT) in
grade 3 nonhematologic toxicity was mucositis (30% of patients), patients who show responses to chemotherapy. Although this experi-
which was attributed to the radiotherapy. With a median follow-up ence is very limited, there is some suggestion that there may be benefit
of 32 months, the study reported a 2-year OS of 78%, which in some patients.
compares very favorably with the historical control group, which Infection with HTLV-1 can cause ATL. Nineteen patients with
received radiotherapy alone (45%). Increasingly, many physicians acute or lymphomatous forms of ATL were treated with oral zidovu-
are considering combined-modality therapy as the best upfront treat- dine (200 mg five times daily) and IFN-α (Intron A; 5–10 million
ment for this disease, despite the potentially significant associated units subcutaneously each day). Seven of these patients either relapsed
toxicity. or were refractory to combination chemotherapy. Major responses
Newer approaches for patients with advanced NKTCLs have were achieved in 58% of the patients (11 of 19), including CR in
explored integrating L-asparaginase into a dexamethasone (steroid), 26% (5 of 19). Four patients in whom prior cytotoxic therapy had
methotrexate, ifosfamide, and etoposide-based backbone (SMILE). failed experienced major responses, two of which were CRs. Six
Yong et al treated 18 patients that were refractory to CHOP with patients have survived for more than 12 months, with the longest
L-asparaginase, vincristine, dexamethasone, and involved field radio- remission since the discontinuation of treatment lasting more than
therapy. The ORR was 83.3%, with 10 (55.6%) of the patients 59 months. A recent metaanalysis evaluated 116 patients with acute
achieving CR, and five (27.8%) achieving partial response (PR). The ATL, 18 patients with chronic ATL, 11 patients with smoldering
5-year OS rate was 55.6%. Results of the preliminary clinical study ATL, and 100 patients with ATL lymphoma. The 5-year OS rates
indicated that the L-asparaginase–based salvage regimens significantly were 46% for 75 patients who received first-line antiviral therapy
improved the RR and 5-year survival rate. A prospective phase II (p = .004), 20% for the 77 patients who received first-line chemo-
trial has been reported with the SMILE regimen in patients with therapy, and 12% for the 55 patients who received first-line chemo-
newly diagnosed stage IV or relapsed refractory NKTCLs. Among therapy followed by antiviral therapy. The metaanalysis suggested that
the 39 patients treated, 29 (74%) completed the planned treatment. patients with acute, chronic, and smoldering ATL significantly ben-
The responses included 15 patients in CR and 14 in PR, with early efited from first-line antiviral therapy, whereas patients with ATL
deaths due to infection in four patients. Infection was the most lymphoma experienced a better outcome with chemotherapy. In
commonly observed toxicity, seen in 41% of the patients. Based on acute ATL, 82% of patients were alive at 5 years with antiviral
these studies, we conclude that L-asparaginase may have a role either therapy, and 100% of patients with chronic and smoldering ATL
in the upfront setting or for patients with relapsed or refractory were alive at 5 years. Multivariate analysis showed that first-line
disease. antiviral therapy significantly improved OS (HR = 0.47; 95% CI,
Efforts to find approaches with a more favorable safety profile have 0.27–0.83; p = .021). Prospective studies are warranted to better
led to the development of regimens built on drugs that are not define the role of antiviral therapy in treatment of ATL.
affected by P-glycoprotein. The GELOX regimen (gemcitabine, Given the activity of the anti-cc chemokine receptor 4 antibody
oxaliplatin, and L-asparaginase) with involved field radiotherapy (CCR4) mogamulizumab in ATL, a randomized phase II study
sandwiched between chemotherapy was studied in patients with stage explored integration of the biological into the mLSG15 regimen (the
IE/IIE extranodal NKTCL (EN-NKTCL) by the Chinese. The VCAMP/AMP/VECP regimen discussed earlier). Fifty-three patients
prospective study reported a ORR of 96.3% with a 74% rate of CR. with acute, lymphomatous, and chronic ATL were randomized to the
Grade 3 or 4 toxicities were minimal, and no treatment-related deaths mLSG15 (n = 24) or mLSG15 plus mogamulizumab (n = 29) regi-
occurred. The rates of 2-year OS and PFS were both 86%, with mens. The respective ORR and CR rates were 86% and 52% in the
patients achieving a CR doing substantially better than patients not mogamulizumab-containing arm, and 75% and 33% in the sLSG15
in CR. These data, while now being studied in larger patient popula- alone arm. While the PFS was improved in the mogamulizumab arm
tions, is promising, and may afford a new and improved approach to (8.5 vs. 6.3 months), there was no difference in OS. In addition,
patients with EN-NKTCL. there was substantially more toxicity in the antibody-containing arm,
raising issues regarding how best to optimally integrate novel drugs
Adult T-Cell Leukemia/Lymphoma: Role of such as mogamulizumab into standard cytotoxic regimens like
Antiviral Agents mLSG15.
The results of traditional chemotherapy in patients with ATL, like in
other forms of PTCL, have been uniformly poor, leading to a con- Angioimmunoblastic T-Cell Lymphoma: The Role of
sensus recommendation to enroll patients when possible in a clinical Cyclosporin and Rituximab
trial in either the upfront or relapsed or refractory setting. This rec- AITL is one of the most common forms of PTCL, with peculiar
ommendation is relevant for patients with most subtypes of PTCL. clinical and pathologic features. Although the normal counterpart has
Although there is again no standard of care for these patients, the been recently identified as the T FH cell, the nonneoplastic cells typi-
general sentiment is that CHOP-based chemotherapy regimens are cally represent the quantitatively major component of AITL. Clini-
inadequate. Owing to the comparatively higher incidence of ATL in cally the manifestations of the disease reflect a dysregulated immune
Japan, many studies regarding the management of ATL come from and/or inflammatory response rather than being the direct complica-
Asia. The Japanese evaluated a complex combination regimen of tion of aberrant tumor growth, supporting the concept of a paraneo-
VCAP (vincristine, cyclophosphamide, doxorubicin [Adriamycin], plastic immunologic dysfunction. Despite the use of different
and prednisone), AMP (doxorubicin [Adriamycin], ranimustine intensive anthracycline-based chemotherapies, AITL is an aggressive
[MCNU], and prednisone), and VECP (vindesine, etoposide, carbo- disease compared with other PTCLs, for which the optimal thera-
platin, and prednisone) against CHOP-14 in ATL. A total of 118 peutic strategy is still not defined. Given the considerable immune
patients were enrolled in the trial and treated with either six courses dysregulation present in AITL, the possible role of cyclosporine A
of VCAP-AMP-VECP every 4 weeks or eight courses of biweekly (CsA) has been investigated in a small number of patients. Twelve
CHOP. The CR rate was higher in the VCAP-AMP-VECP arm than patients were treated with the immunomodulatory CsA, 10 of whom
in the CHOP-14 arm (40% vs. 25%, respectively), and the had failed prior therapy with either chemotherapy and/or steroids
progression-free survival (PFS) at 1 year was 28% in the VCAP- (one to two prior regimens). Two patients were untreated because of
AMP-VECP arm compared with 16% in the CHOP arm. The OS age or comorbid conditions. Three patients achieved CR and five a
at 3 years was 24% in the VCAP-AMP-VECP arm and 13% in the PR for an overall RR of 67%, suggesting a possible role for CsA in
CHOP arm. Overall, the toxicity in the VCAP-AMP-VECP arm was this setting. In AITL, symptoms linked to B-lymphocyte activation