Page 1457 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 80 Clinical Manifestations, Staging, and Treatment of Follicular Lymphoma 1297

signaling pathway are logical targets for therapy in FL. In addition, high/intermediate-grade and 10 patients with MCL, 31 of whom had
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idelalisib is approved for the treatment of rituximab-refractory fol- relapsed following previous ASCT. Patients received a conditioning
licular lymphoma and clinical trial data has been presented for kinase regimen consisting of alemtuzumab, fludarabine, and melphalan, and
inhibitors that target Bruton tyrosine kinase (BTK), 106,107 and spleen received short course cyclosporin as graft-versus-host disease (GVHD)
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tyrosine kinase (SYK). Novel agents are being examined in combi- prophylaxis. The use of this conditioning regimen was associated
nation with monoclonal antibodies and chemotherapy. Since a hall- with a low incidence of GVHD and the treatment related mortality
mark of FL is overexpression of BCL2, this protein is also a logical was decreased in patients with low-grade compared with higher
target for small molecule inhibitors that can inhibit the antiapoptotic grade histology. The 3-year PFS was 65% for patients with low-grade
activity of BCL2. Clinical responses have been observed in the phase lymphoma, 50% for patients with MCL and 34% for high-grade
I study examining the efficacy of navitoclax in lymphoid malignan- lymphoma (p = .002). Donor lymphocyte infusion (DLI) was given
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cies. The next generation agent venetoclax is now approved in to 36 patients, 21 for relapsed or persistent disease and 15 for persis-
chronic lymphocytic leukemia and clinical trials are ongoing in FL, tence of mixed chimerism. The use of DLI to treat relapse after aSCT
both alone and in combinations. is solely dependent upon the existence of a graft versus lymphoma
effect. In seven patients with FL and small lymphocytic lymphoma
who had relapsed after prior aSCT, six patients responded and four
Allogeneic Bone Marrow Transplant maintained CR for 43–89 months. The effectiveness of DLI to treat
relapse after aSCT provides very strong evidence for a graft versus
There is a trend towards increasing use of allogeneic SCT (aSCT) lymphoma effect that can be exploited in indolent lymphomas. 114,115
in the management of indolent lymphomas. In a report of the The role of RIC aSCT has been evaluated by Cancer and Leukemia
International Bone Marrow Transplant Registry (IBMTR), results Group B in a phase II study to evaluate the safety and efficacy in
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after SCT are described for 904 patients with FL. Among these patients with recurrent low-grade B-cell malignancies, including 16
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patients, 176 patients underwent aSCT, 131 patients underwent patients with FL. The 3-year TRM was 9% and the 3-year OS
ASCT using purged stem cells and 597 using purged autologous stem was 81%. The incidence of grade II–IV acute GVHD was 29%, and
cells. The treatment related mortality (TRM) in these three groups extensive chronic GVHD was 18%.
was 30%, 14% and 8% respectively. Disease recurrence occurred in
21%, 43% and 58% and 5-year overall survival was 51%, 62% and
55% respectively. The use of TBI containing regimens was associated SUGGESTED READINGS
with increased TRM but decreased risk of relapse. The use of aSCT
was associated with increased TRM, but significantly lower risk of Dave SS, Wright G, Tab B, et al: Prediction of survival in follicular lymphoma
disease recurrence in keeping with a graft versus lymphoma effect in based on molecular features of tumor-infiltrating immune cells. N Engl J
this disease. Trends suggest that outcomes are improving and this is Med 351:2159–2169, 2004.
highly likely to continue with the increased use of reduced intensity Friedberg JW, Byrtek M, Link BK, et al: Effectiveness of first-line manage-
conditioning regimens that have become used increasingly since the ment strategies for stage I follicular lymphoma: analysis of the National
time this registry data was collated. Long-term PFS has been observed LymphoCare Study. J Clin Oncol 30:3368–3375, 2012.
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after aSCT even in patients with refractory FL. In 29 patients with Gopal AK, Kahl BS, de Vos S, et al: PI3Kdelta inhibition by idelalisib in
FL, 11 of whom had refractory disease, the nonrelapse mortality was patients with relapsed indolent lymphoma. N Engl J Med 370:1008–1018,
24% and there was a 23% incidence of relapse. The 5-year OS was 2014.
58% with 53% event-free survival. A group of patients with very poor Kridel R, Sehn LH, Gascoyne RD: Pathogenesis of follicular lymphoma.
outcome are those patients who have relapsed after previous ASCT. J Clin Invest 122:3424–3431, 2012.
The outcome following myeloablative aSCT of 114 such patients has Okosun J, Bodor C, Wang J, et al: Integrated genomic analysis identifies
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been reported from the IBMTR. The treatment related mortality recurrent mutations and evolution patterns driving the initiation and
was 22% and the probability of disease progression was 52% at 3 progression of follicular lymphoma. Nat Genet 46:176–181, 2014.
years. The use of TBI conditioning regimens and achievement of Salles G, Seymour JF, Offner F, et al: Rituximab maintenance for 2 years in
CR at the time of aSCT were associated with improved outcome. patients with high tumour burden follicular lymphoma responding to
The use of reduced intensity conditioning regimens appears to be rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled
associated with improved outcome. In 20 such patients, there was trial. Lancet 377:42–51, 2011.
only one treatment related mortality from fungal infection and
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the 3-year PFS was an excellent 95%. The outcome following
reduced intensity conditioning transplant regimen incorporating REFERENCES
alemtuzumab immunosuppressive therapy has been reported for 81
patients with lymphoma and included 41 with low-grade, 37 with For the complete list of references, log on to www.expertconsult.com.