Lymphoma

On August 22, 2008, the US Food and Drug Administration (FDA) granted marketing approval (licensure) to romiplostim (Nplate, Amgen Inc) for the treatment of thrombocytopenia in patients with chronic immune (idiopathic) thrombocytopenic purpura (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.

An 8-year randomized, controlled phase III clinical study has shown that a patient-specific therapeutic vaccine, BiovaxID, significantly prolongs disease-free survival in follicular non-Hodgkin’s lymphoma. The study, featured in ASCO’s plenary session, found that patients who received the vaccine experienced a median disease-free survival of approximately 44 months compared to approximately 30 months for those who received a control vaccine-an increase of 47% (abstract P2).

The addition of rituximab (Rituxan) to systemic chemotherapy has improved the response rates, progression-free survival, and overall survival of patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) compared to chemotherapy alone. In the front-line setting, the use of rituximab is changing the biology and clinical behavior in DLBCL patients who fail to respond or relapse following chemoimmunotherapy.

Chemoimmunotherapy has been the most significant step in recent years to improving overall survival (OS) and progression-free survival (PFS) rates in patients with diffuse large B-cell lymphoma ­(DLBCL).[1] Despite this major therapeutic advance, a significant proportion of patients will relapse or remain refractory to initial chemoimmunotherapy. The pivotal PARMA trial confirmed the place of high-dose chemotherapy and autologous stem cell transplant (ASCT) as the optimum salvage treatment.

Drs. Hernandez-Ilizaliturri and Czuczman should be complimented on their comprehensive review of management options for patients with relapsed and refractory diffuse large B-cell lymphoma (DLBCL).

According to published statistics, in 2008 approximately 66,120 new cases of non-Hodgkin lymphoma (NHL) were diagnosed and 19,160 lymphoma patients died from their disease despite currently available treatment.[1] Diffuse large B-cell lymphoma (DLBCL), the most common type of B-cell NHL, has an aggressive clinical course and, as demonstrated by gene-profiling studies, can be further divided into subgroups with distinct biologic characteristics and prognoses.[2]

Sargramostim (Leukine) paired with a patient-specific immunotherapy mitumprotimut-T (Specifid), failed to reduce time to remission in patients with CD20+ follicular lymphoma following therapy with rituximab (Rituxan), according to the highly anticipated results of a phase III clinical trial.

Cephalon, Inc, announced that the US Food and Drug Administration (FDA) has approved injectable bendamustine hydrochloride (Treanda) for the treatment of patients with indolent B-cell non-Hodgkin lymphoma (NHL) that has progressed during or within 6 months of treatment with rituximab (Rituxan) or a rituximab-containing regimen. The data supporting the FDA approval show that bendamustine is effective, has a tolerable side effect profile in patients with indolent NHL, and that treatment results in a high durable response rate. In March of this year, bendamustine received approval for the treatment of patients with chronic lymphocytic leukemia, the most common form of leukemia in the United States.

Results of the first clinical study examining the use of fostamatinib disodium, an investigational treatment that targets a protein called SYK (spleen tyrosine kinase), showed that the new agent represents a safe and novel therapeutic approach that should be further developed for the treatment of B-cell non-Hodgkin lymphoma.

The results of an international randomized trial found that the use of dexamethasone in the induction phase of combination chemotherapy led to a one-third reduction in the risk of relapse as compared with the standard corticosteroid, prednisone, translating into a significant benefit in terms of event-free survival in children with acute lymphoblastic leukemia.

Burkitt lymphoma (BL) is a unique B-cell lymphoma characterized by a high proliferation rate and cytogenetic changes related to c-myc proto-oncogene overexpression. Burkitt lymphoma is a highly aggressive B-cell lymphoma that is most frequently seen in children and young adults in endemic areas.

Hodgkin lymphoma (HL) is one of the most curable malignancies in adults. However, survival rates for elderly patients with HL (often defined as ≥ 60 years of age) are inferior to those achieved by younger populations.

In this issue of ONCOLOGY, Evens et al present a thoughtful and compelling argument that Hodgkin lymphoma in elderly patients deserves to be a focus for clinical research.

As the authors have correctly pointed out, Hodgkin lymphoma (HL) in elderly patients is an orphan disease that has been the subject of very few specific studies, particularly regarding treatment.

Socioeconomic factors and the type of treatment received have an impact on a non-Hodgkin lymphoma (NHL) patient’s risk of dying.

This supplement to ONCOLOGY provides a comprehensive look at state-of-the-art management of three of the most prevalent hematological malignancies in the US today.

CHICAGO-Increasing the dose density of rituximab in the R-CHOP-14 regimen yields better rituximab (Rituxan) pharmacokinetics and improved clinical outcomes among older adults with high-risk diffuse large B-cell lymphoma (DLBCL), reported lead investigator Michael G.M. Pfreundschuh, MD.

The investigational tyrosine kinase inhibitor bosutinib has an acceptable safety profile and appears to be efficacious among patients with chronic-phase chronic myelogenous leukemia who have intolerance or resistance to other TKIs, according to new data presented at ASCO 2008 (abstract 7001).

An analysis of 2,459 mantle cell lymphoma patients diagnosed from 1992 (when the disease was first recognized as a separate type of lymphoma) to 2004 showed that men were more than twice as likely to be diagnosed as women, Caucasians had the highest risk of all ethnic groups, and people aged 70 to 79 were more likely to be diagnosed than all other age groups (Cancer, published online July 7, 2008, DOI: 10.1002/cncr.23608).

CHICAGO-Ongoing trials are still clarifying the optimal approach to management after induction therapy for non-Hodgkin’s follicular lymphoma. In the meantime, patients and physicians are left to ponder whether maintenance rituximab (Rituxan) should be used routinely in all cases. Leading researchers in hematology debated this topic in an education session at ASCO 2008.

CHICAGO-Temsirolimus (Torisel) prolongs progression-free survival in patients with relapsed and/or refractory mantle cell lymphoma when compared with commonly used conventional therapies, finds an international phase III trial.

ATLANTA-Interim results of an international phase III study show that rituximab (Rituxan)-based salvage chemotherapy results in high response rates in patients with CD20-positive relapsed/refractory diffuse large B-cell lymphoma (DLBCL) allowing for stem-cell transplantation.

The introduction of imatinib mesylate (Gleevec) has dramatically changed the management and prognostic outlook of patients with chronic myeloid leukemia (CML).

Chronic myelogeneous leukemia (CML) is a biologically unique neoplasm resulting from a mutation producing a single abnormal protein that induces unregulated proliferation of myelopoiesis. Imatinib mesylate (Gleevec) profoundly inhibits the chimeric bcr/abl tyrosine kinase, and has dramatically improved the outlook for patients with CML in chronic phase.

The introduction of the tyrosine kinase inhibitor imatinib mesylate (Gleevec) has profoundly changed the treatment paradigm for patients with chronic myelogenous leukemia (CML).

Long-term results of a German randomized trial suggest that a novel escalated-dose regimen may replace the current chemotherapy standard of care for treatment of advanced-stage Hodgkin lymphoma. Volker Diehl, MD, of the University of Cologne, Germany, presented 10-year follow-up data on behalf of the German Hodgkin Study Group at ASH 2007 (abstract 211).

Among Ph+ chronic myelogenous leukemia patients in accelerated phase with imatinib (Gleevec) resistance or intolerance, treatment with nilotinib (Tasigna) rapidly produced significant responses and was generally well tolerated in an open-label pivotal phase II study

Study results presented at ASH 2007 showed efficacy of the novel tyrosine kinase inhibitor dasatinib (Sprycel) in imatinib (Gleevec) resistant or intolerant chronic myelogenous leukemia patients in chronic, accelerated, and blast phase

In a significant proportion of imatinib (Gleevec)-resistant chronic-phase chronic myelogenous leukemia patients with Bcr-Abl mutations, nilotinib (Tasigna) treatment results in hematologic, cytogenetic, and molecular responses

Use of rituximab (Rituxan) in the pre-transplant setting significantly boosts both progression-free and overall survival for patients with diffuse large B-cell lymphoma (DLBCL), without impacting engraftment or treatment-related mortality