February 2016, Vol 7, No 1

Society meetings, such as the recent American Society of Hematology (ASH) annual meeting, generate a lot of clinical-related excitement regarding new treatment options, protocols, and pathways for hematologic cancers.

The use of therapy with chimeric antigen receptor (CAR)-modified T-cells consistently demonstrated activity in advanced hematologic malignancies, including different types of lymphoma, in multiple trials reported at ASH 2015.

The oral, investigational, small-molecule BCL-2 inhibitor venetoclax has shown excellent and durable responses in patients with relapsed or refractory chronic lymphocytic leukemia (CLL). All patients in the trial harbored the 17p deletion (del 17p), which signals poor prognosis.

Immunotherapy is generating great excitement in melanoma and non-small-cell lung cancer (NSCLC). The FDA approvals of checkpoint inhibitors in these tumor types, as well as encouraging preliminary results in other solid tumors, have paved the way for studying these therapies in hematologic cancers.

Treatment with CD19-targeted immunotherapy blinatumomab (Blincyto) as a single agent showed antileukemic activity in patients with minimal residual disease (MRD) Philadelphia chromosome (Ph)-positive B-cell precursor acute lymphoblastic leukemia (ALL) whose disease progressed after or was intolerant to a second-generation or later tyrosine kinase inhibitor (TKI). The results were presented at ASH 2015.

Ibrutinib (Imbruvica) significantly reduced the risk for disease progression or death compared with standard treatment with chlorambucil (Leukeran) in older (aged ≥65 years) treatment-naive patients with chronic lymphocytic leukemia (CLL). Ibrutinib achieved a 91% reduction in the risk for disease progression and an 84% reduction in the risk for death compared with chlorambucil.

Idelalisib (Zydelig) reduced the risk for disease progression and death when added to bendamustine (Treanda) plus rituximab (Rituxan) versus bendamustine plus rituximab alone in patients with relapsed or refractory chronic lymphocytic leukemia (CLL), according to the results of a randomized, double-blind, placebo-controlled, phase 3 late-breaking trial presented at ASH 2015.

Dose-optimized nilotinib (Tasigna) increased the rates of major molecular response in patients with newly diagnosed chronic myeloid leukemia (CML) in the chronic phase (CP) in the Evaluating Nilotinib Efficacy and Safety in Clinical Trials-Extending Molecular Responses (ENESTxtnd) study. According to the final results of this study presented at ASH 2015, the cumulative major molecular response rates were 70.8% by 12 months and 81.0% by 24 months in patients managed with the dose optimization strategy.

With the accelerated FDA approval in December 2015 of the anti-CD38 monoclonal antibody daratumumab (Darzalex) for patients with multiple myeloma who received ≥3 previous therapies, studies of the drug presented at ASH 2015 were of great interest.

The immunostimulatory monoclonal antibody elotuzumab (Empliciti), which was approved by the FDA in December 2015, is being studied in combination with immunomodulatory drugs and proteasome inhibitors in patients with relapsed or refractory multiple myeloma. Results presented at ASH 2015 show continued benefit from these regimens.