Hematologic Oncology

It is easy to anticipate that as the complex biology of CLL continues to unfold, new prognostic and predictive biomarkers will be recognized. The discovery of genetic mutations that are key regulators of the development, growth, and proliferation of CLL leukemic cells augurs an alluring future.

One strategy would be to consider “early treatment” for patients with deletion 17p, with the goal being to delay disease progression. This strategy is currently being explored in several prospective clinical trials employing treatment regimens such as FCR, lenalidomide (Revlimid), alemtuzumab (Campath), ofatumumab (Arzerra), and others.

This review will discuss the pathophysiology associated with the del(17p13.1) interphase cytogenetic abnormality, the current generally poor outcomes in affected patients, currently approved therapeutic agents, and new agents now undergoing investigation.

The FDA today approved omacetaxine mepesuccinate (Synribo) for the treatment of adults with chronic myeloid leukemia (CML) who are resistant to other therapies.

A new review of the literature shows that melanoma is substantially more common in immunosuppressed patients, including those with prior solid organ transplant and individuals with lymphoma.

Physicians now have the luxury of focusing attention on maximizing outcomes that are already quite favorable, and of devoting more attention to improving quality of life and addressing questions of cost-effectiveness.

Resistance due to new mutations in the genes coding for the targeted proteins, as well as to changes in other signaling pathways, often develops, and newer drugs and perhaps combination approaches may be needed.

Is it reasonable to start all new CML patients on treatment with imatinib alone and continue the drug indefinitely in those who fare well, or should one start treatment with one of the newer agents or possibly with imatinib in combination with another anti-CML agent in order to secure the best possible outcome for an individual patient?

Ariad Pharmaceuticals followed last month’s request to the FDA for accelerated approval of the BCR-ABL inhibitor ponatinib with a similar request to the European Medicines Agency.

The most interesting developments in drug therapy for adult ALL are occurring in two fields: (1) molecularly targeted therapies and (2) the use of antibodies, conjugated antibodies, or antibody constructs.

It is clear that the management of adult patients with ALL is an area in which little progress has been made in the last 30 years. Given the disappointing outcomes, the field is one that lends itself to the study of the incorporation of novel agents, including monoclonal antibodies and tyrosine kinase and proteasome inhibitors, as well as to further study of allogeneic transplant.

In this review, we will discuss the management of ALL in the adult population, in the context of the recently published guidelines from the NCCN. We will focus in particular on the strides being made in salvage and targeted approaches.

A study comparing dasatinib to imatinib in patients with chronic myeloid leukemia found that the second-generation TKI dasatinib yielded better remission and molecular response rates than imatinib, but these did not result in better survival outcomes.

The FDA approved the tyrosine kinase inhibitor bosutinib (Bosulif) to treat Philadelphia chromosome–positive chronic myelogenous leukemia (CML).

A common genetic mutation in BIM appears to play a role in resistance to tyrosine kinase inhibitors in chronic myeloid leukemia (CML) and EGFR-mutated NSCLC.

The FDA has approved vincristine sulfate liposome injection (Marqibo) to treat adults with Philadelphia chromosome–negative acute lymphoblastic leukemia (ALL).

A new study finds that adding rituximab maintenance to R-CHOP induction is an effective treatment for older patients with mantle-cell lymphoma.

Ariad Pharmaceuticals has asked the FDA for an accelerated approval of the BCR-ABL inhibitor ponatinib, based on promising data from ongoing phase II trials.

Acute myeloid leukemia (AML) encompasses multiple disease entities that differ with regard to marrow morphology, cytochemistry, immunophenotype, pretreatment clinical characteristics, and treatment outcome.

Prognostic factors in acute myeloid leukemia (AML) may be subdivided into those related to patient characteristics and general health condition, and those related to characteristics of the tumor.

Last week the US Food and Drug Administration approved carfilzomib (Kyprolis) to treat patients with multiple myeloma who have received at least two prior therapies, including treatment with bortezomib (Velcade) and an immunomodulatory therapy.

Three-year results from the ENESTnd trial show continued superiority of nilotinib over imatinib in patients with Philadelphia chromosome-positive chronic myeloid leukemia (CML) in chronic phase, according to a new paper published online ahead of print in Leukemia in June.

Nilotinib offers good results for patients with Philadelphia chromosome-positive chronic myeloid leukemia (CML) in chronic phase who are resistant or intolerant of imatinib, according to 48-month follow-up results of a phase II study.

Observations made in the study of the leukemias have contributed to our understanding of malignancy in general and to our ability to treat cancer patients with drugs.

The article by Drs. Stein and Tallman is an excellent summary indicating that several different approaches may lead to the cure of acute promyelocytic leukemia (APL).

The management of patients with acute promyelocytic leukemia (APL) has been transformed over the course of the last two decades following the introduction of successful molecularly targeted therapies-all-trans retinoic acid (ATRA) and arsenic trioxide (ATO)- which act in concert to induce degradation of the PMLRARα oncoprotein formed by the chromosomal translocation t(15;17)(q22;q21).

The treatment of APL in the modern era is a success of modern hematology. In this review we have attempted to plant the seeds of understanding regarding how diagnosis and treatment of APL will be pursued over the next decade.

CancerNetwork speaks with Hagop Kantarjian, MD, M.D. Anderson Cancer Center, who shares his impressions of some of the highlights of this year’s ASCO meeting with regard to hematologic malignancies.

Impressive interim results from a phase Ib/II trial of ibrutinib, a selective Bruton tyrosine kinase inhibitor, in patients with chronic lymphocytic leukemia (CLL) were reported at ASCO.

Updated clinical data from the pivotal phase II global PACE trial of ponatinib confirm its impressive antileukemic activity in patients with chronic myeloid leukemia or Philadelphia-chromosome-positive acute lymphoblastic leukemia at all stages who are resistant or intolerant to dasatinib or nilotinib.