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Editors from Journal Watch Oncology and Hematology attended the 53rd meeting of the American Society of Hematology (ASH) held recently in San Diego (ASH 2011) and reported some of the highlights. In this final installment, Dr. Michael Williams discusses the latest research in lymphoma, chronic lymphocytic leukemia (CLL), myelodysplastic syndrome (MDS), and stem cell transplantation.
Radioimmunotherapy (RIT) is a highly active treatment for patients with relapsed follicular lymphoma (FL). To test its benefit as the immunotherapeutic complement to CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy for initial treatment of patients with advanced-stage symptomatic FL, a phase III U.S. Cooperative Group compared standard rituximab (R)-CHOP-21 versus CHOP followed by I-131-tositumomab (CHOP-RIT) in 554 patients (Abstract 98). At median follow-up of 4.9 years, no difference was found between the two groups in rates of complete response (CR), overall response (OR), or 2-year progression-free survival (PFS). Two-year overall survival (OS) was similarly high for the R-CHOP and CHOP-RIT groups (97% and 93%); both groups also experienced similar rates of second cancers (8.7% and 8.3%) and myelodysplastic syndrome or acute myeloid leukemia (1.1% and 2.7%).
Patients with mantle cell lymphoma (MCL) are highly responsive to a variety of immunochemotherapy induction regimens, but they typically experience disease progression within 1 to 3 years. A multicenter clinical trial compared R-CHOP versus R-FC (fludarabine plus cyclophosphamide) followed by a second randomization to maintenance rituximab (MR) versus interferon alfa for patients >60 with stage II–IV untreated MCL who were not eligible for hematopoietic stem-cell transplant consolidation (Abstract 439). The objective respective rate favored R-CHOP over R-FC (87% vs. 78%; P=0.051), with a significant OS benefit for R-CHOP (64 months vs. 40 months; P=0.0072). No difference in OS was seen between the two maintenance arms, but a clearly improved outcome was seen for patients who received R-CHOP and MR (4-year survival, 87%), establishing MR as an appropriate therapy in this setting. R-FC was more toxic and was associated with inferior survival in this older MCL population.
Histone deacetylase inhibitors are a newly available class of agents for the treatment of patients with cutaneous T-cell lymphomas and peripheral T-cell lymphoma (PTCL). A multinational phase II trial of the selective HDAC inhibitor romidepsin tested its efficacy and safety in patients with heavily pretreated (median 2 prior therapies, range 1–8) relapsed or refractory PTCL-NOS (not otherwise specified), angioimmunoblastic T-cell lymphoma, and ALK1-negative anaplastic large cell lymphoma (Abstract 591). Patients received romidepsin weekly for 3 weeks of each 4-week cycle for up to 6 cycles; responders and those with stable disease (SD) were eligible to continue treatment beyond 6 cycles. Of 130 patients, 16% achieved CR, 12% partial response, and 18% SD. The median duration of response was 17 months (range, <1 to >34 months), with responses observed in all three PTCL subtypes. Grade 3–4 neutropenia was observed in 18% of patients, thrombocytopenia in 25%, and infections in 15%. Romidepsin is thus confirmed as an active agent in PTCL, leading the authors to recommend testing in the front-line setting and in combination regimens.
Bruton tyrosine kinase (BTK) is a critical component of the B-cell receptor signaling pathway in malignant B cells. The BTK inhibitor (BTKI) PCI-32765 induces apoptosis and altered stromal adhesion and has demonstrated impressive clinical responses in preliminary studies of CLL and B-cell lymphomas. In a multicenter phase Ib/II trial, the oral BTKI was tested at two doses (420 mg/day and 840 mg/day) in 61 patients with relapsed or refractory CLL/small lymphocytic lymphoma (SLL; Abstract 983). Most patients had at least one poor-risk factor. As in prior studies, transient lymphocytosis was observed at treatment initiation, representing mobilization of CLL cells into the circulation. At 10-month follow-up, the ORR in patients who received the lower dose was 70% (up from 48% at 6 months); at 6-month follow-up, the ORR in patients who received the higher dose was 44%. Two patients stopped therapy because of adverse events, and six required dose reduction. Responses occurred in patients with poor-risk factors, including del(17p). Further reports of this very promising agent for relapsed CLL/SLL will be of great interest, as will a study of front-line BTKI therapy now in progress.
Peripheral blood stem cell (PBSC) allografts from related donors improve patient outcomes but are associated with higher rates of graft-versus-host disease (GVHD) than are donor bone marrow cell grafts. To compare outcomes associated with PBSC versus bone marrow grafts from unrelated donors, investigators conducted a multicenter, phase III, randomized trial involving patients with acute or chronic myeloid malignancies (Abstract 1). A total of 551 patients were randomized to receive filgrastim-mobilized PBSC or bone marrow transplantation; adherence to the assigned therapy was >90% in each group. No differences in patient outcomes or OS were observed, although chronic extensive GVHD occurred more often in recipients of PBSC grafts (46% vs. 31%). Acute GVHD, rates of relapse for either low- or high-risk malignancy cohorts, and nonrelapse mortality also did not differ between the two graft sources.
This study (Abstract 3) was reviewed in a prior summary: New Insights into Myelodysplastic Syndrome Pathogenesis (JW Oncol Hematol Sep 27 2011).
This study (Abstract 590) was reviewed in a separate summary (JW Oncol Hematol Jan 31 2012).