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Report from the 55th American Society of Hematology Annual Meeting and Exposition — Hematologic Malignancies

Meeting Report |
January 16, 2014

Report from the 55th American Society of Hematology Annual Meeting and Exposition — Hematologic Malignancies

  1. Michael E. Williams, MD, ScM

Highlights of the latest research

  1. Michael E. Williams, MD, ScM

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.

Lenalidomide for Multiple Myeloma Patients Ineligible for Stem-Cell Transplantation

The combination of melphalan, prednisone, and thalidomide (MPT) has been a standard front-line treatment for patients with newly diagnosed multiple myeloma who are not eligible for autologous stem-cell transplantation (ASCT). To evaluate the use of the noncytotoxic regimen of lenalidomide (L) and weekly dexamethasone (d) in this setting, Facon and colleagues conducted a phase III, three-arm, multinational, randomized, open-label trial of MPT versus either Ld given until disease progression or Ld given for a total of 18 cycles (72 weeks) in 1623 patients (abstract 2).

At a median follow-up of 37 months, Ld recipients achieved a 28% reduction in risk for disease progression or death, as well as a significant improvement in overall response rate, duration of response, and progression-free survival. More grade 3 or 4 neutropenia episodes, but fewer infections, occurred with MPT than with Ld.

Idelalisib for Relapsed or Refractory Chronic Lymphocytic Leukemia

Idelalisib is an oral inhibitor of PI3Kδ — a critical component of the B-cell receptor signaling pathway — that was shown to be highly active in patients with relapsed or refractory chronic lymphocytic leukemia (CLL). Now, Furman and colleagues have conducted a phase III, multinational, randomized trial that compared Idelalisib plus rituximab (IR) versus placebo plus rituximab (R) in 220 previously treated CLL patients (median number of prior therapies, 3; range, 1–12) who were not candidates for cytotoxic chemotherapy due to comorbid illness or cytopenias (abstract LBA-6). Most patients had poor-risk disease, including del(17p)/p53 mutation (44%) and unmutated immunoglobulin heavy chain variable genes (84%).

Outcomes were significantly better with IR than with R: overall response rate (81% vs. 13%), progression-free survival at 24 weeks (93% vs. 46%), lymph node response (93% vs. 4%), and overall survival (hazard ratio, 0.28). Adverse events more commonly observed with IR included fatigue, cough, and elevated liver transaminase; treatment was discontinued because of toxicity by 8.2% of IR recipients and 10.3% of R recipients. The study confirms very high responses to IR in heavily pretreated patients with CLL, including those with adverse genetic subtypes.

Ibrutinib for Relapsed or Refractory Waldenstrom's Macroglobulinemia

The Bruton tyrosine kinase inhibitor ibrutinib has demonstrated high clinical activity in relapsed and refractory chronic lymphocytic leukemia and mantle cell lymphoma. Preclinical studies demonstrating the activity of ibrutinib in Waldenstrom's macroglobulinemia (WM, a B-cell lymphoplasmacytoid lymphoma) led Treon and colleagues to conduct a prospective, multicenter trial of oral ibrutinib (420 mg daily) in 63 patients with relapsed or refractory WM (abstract 251).

Patients achieved a rapid reduction of serum immunoglobulin M and improved hematocrit, with an overall response rate of 83% and a major response rate of 65%; 87% of patients continued on treatment at a median of nine cycles. Treatment was well tolerated, with no patient discontinuing therapy due to toxicity. Patients with mutations in the CXCR4 gene had lower response rates, suggesting a mechanism for risk-adapted ibrutinib therapy.

Early Relapse of Follicular Lymphoma and High Risk for Death

Despite high response rates to immunochemotherapy, about 20% of patients with follicular lymphoma (FL) experience progression of disease (POD) within 2 years of initial treatment. To determine the outcomes for these patients, Casulo and colleagues retrospectively compared FL patients treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) who had POD within 2 years of diagnosis (early POD) versus those without POD within 2 years (abstract 510). A total of 588 patients from the Lymphocare Database were included. Patients who underwent watchful waiting as initial management were excluded from this analysis.

A total of 21% had early POD and 71% did not (8% were lost to follow-up). After adjusting for baseline characteristics, early POD was dramatically associated with poor overall survival (HR, 13.3; 95% confidence interval, 7.94–22.4). Even after adjusting for Follicular Lymphoma International Prognostic Index (FLIPI) score, early POD was associated with an increased risk for death (HR, 15.4; 95% CI, 9.6–24.7). High lactate dehydrogenase, poor performance status, B symptoms, and bone-marrow involvement were associated with early POD (P<0.05). Early POD may define a biologically and clinically important FL subset for whom new treatment strategies are warranted.

  • Disclosures for Michael E. Williams, MD, ScM at time of publication Consultant / Advisory board Celgene; Genentech; Millennium; Pharmacyclics Speaker's bureau Educational Concepts Group; ION; Research to Practice; Xcenda Grant / research support Allos Therapeutics; AstraZeneca; Celgene; Genentech; Gilead; Millennium; Novartis; Onyx; Pharmacyclics; Janssen Editorial boards Current Treatment Options in Oncology

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