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Editors from NEJM Journal Watch Oncology and Hematology attended the recent meeting of the American Society of Hematology (ASH). Here, Dr. Michael Williams describes the latest findings in malignant hematology.
Röllig and colleagues conducted the international, randomized, prospective, placebo-controlled SAL-Soraml trial (abstract 6) to test the use of the multikinase inhibitor sorafenib in conjunction with induction and consolidation chemotherapy for patients with newly diagnosed acute myeloid leukemia. Sorafenib or placebo was continued for 12 months as maintenance therapy for patients in remission who did not proceed to allogeneic stem-cell transplant consolidation. For 267 patients who were randomized and treated, the complete response rates (CRR) with sorafenib or placebo were 60% and 59%, respectively. However, at median 3-year follow-up, event-free survival (the primary endpoint) was superior with sorafenib (20.5 vs. 9.2 months; P=0.013), as was the 3-year relapse-free survival rate (38% vs 56%; P=0.017). Sorafenib recipients had higher risk for fever, bleeding events, and hand-foot syndrome.
Duehrsen and colleagues conducted the prospective, multicenter PETAL trial (abstract 391), in which patients with B- or T-cell lymphoma (non-Burkitt) underwent interim positron emission tomography (iPET) after 2 cycles of CHOP chemotherapy (if CD20-negative) or rituximab plus CHOP (R-CHOP). Patients with a positive iPET were randomized to dose-intensive therapy versus continued CHOP with or without rituximab. Those with a favorable iPET had a 2-year time to treatment-failure of 79%, versus 47% for unfavorable iPET (P<0.0001). A switch to aggressive chemotherapy did not improve outcome for iPET-positive patients, even among those with diffuse large B-cell lymphoma (DLBCL), indicating primary chemotherapy resistance and a need for alternative strategies.
Sehn and colleagues conducted a multicenter, phase II trial (abstract 392) of iPET after 4 cycles of R-CHOP for newly diagnosed DLBCL. Patients who were iPET-positive were switched to R-ICE chemotherapy for 4 cycles, while iPET-negative patients received an additional 2 cycles of R-CHOP. Patients who were iPET-negative had a higher 4-year progression-free survival (PFS) rate than iPET-positive patients (91% vs. 59%) and a higher overall survival rate (96% vs. 73%). Few iPET-positive patients remitted, suggesting R-ICE was unable to overcome intrinsic chemotherapy-resistance in most of these individuals.
Ruan and colleagues conducted a multicenter, phase II trial (abstract 625) of 38 patients with advanced-stage mantle cell lymphoma who received the doublet of rituximab plus lenalidomide. Treatment included a 12-month induction phase followed by maintenance therapy with reduced-dose lenalidomide and rituximab bimonthly. At a median 2-year follow-up, the overall response rate (ORR) was 84% and the CRR was 53%, with 79% of patients remaining progression-free and continuing therapy (2-year PFS, 84%). Grade 3 or 4 toxicities — including rash in 26% of patients and tumor flare in 11% — occurred only during induction; one secondary malignancy was observed at month 18 of treatment.
Given that 98% of patients with hairy cell leukemia (HCL) carry the BRAFV600E mutation, Park and colleagues conducted a multicenter, phase II trial (abstract 24) of the oral BRAF inhibitor vemurafenib in HCL patients who were resistant to nucleoside analogue therapy or had two or more relapses. Of 20 treated patients, 17 completed the planned 3-month induction. The ORR was 100% and the CRR was 35%. Toxicities included rash in 40% of patients, arthralgia in 30%, and photosensitivity in 20%; all toxicities were grade 1 or 2. Further study of BRAF targeting is warranted for less heavily pretreated patients and, potentially, in previously untreated patients.
Similar results were also found with vemurafenib in a multicenter, phase II Italian trial by Tiacci and colleagues of 26 HCL patients with primary refractory and early- or multiple-relapsed disease (abstract 150).
Eichhorst and colleagues conducted a prospective, multicenter, phase III study (abstract 19) to compare initial therapy with 6 cycles of fludarabine, cyclophosphamide, and rituximab (FCR) versus 6 cycles of bendamustine and rituximab (BR) in fit patients with advanced chronic lymphocytic leukemia and low comorbidities. Those with the poor-risk del(17p) marker were excluded. The ORR in both groups was 98%. However, CRR was significantly higher with FCR than BR (41% vs. 32%), as was achievement of minimal residual disease negativity (74% vs. 63%). Significantly more patients in the BR group were older than 70 and had unfavorable unmutated immunoglobulin heavy-chain variable (IGHV) status, possibly contributing to the variance in treatment response. FCR recipients had higher rates of severe neutropenia (88% vs. 68%), severe infections (40% vs. 25%), and treatment-related mortality (3.9% vs. 2.1%).