PracticeUpdate: Haematology & Oncology

2016 TOP STORIES IN ONCOLOGY 4

Minimal residual disease assessment inAML By Isabel Cunningham, MD W ith no breakthrough therapies for acute myeloid leukaemia (AML) this year, again, and no AML clini- by excision or radiation before it has time to metastasise.

abnormal karyotypes. Only small numbers of the 152 studied for MRD had been fol- lowed over a year, but the early results are encouraging. The authors documented that less than a 4-log reduction in NPM1-mutated cells after induction eventuated in the early relapses and near 60% relapse rate at 1 year that is all too familiar in studies of unstratified AML patients. However, relapse within 2 years occurred in only 20% of those patients in whom reduction exceeded 5 logs. The benefits of our being able to recognise inadequate cell kill right after induction are tremendous. Knowing such results in an individual patient could lead to making earlier decisions about risking transplant or going to experimental therapies. It should also prompt doctors to search for an unrecognised leukaemic tumour that could have grown silently in any organ through therapy. Finding a resistant tumour using PET/CT or gallium would enable ablation

Another valuable feature of this French study is its requirement that the search for a transplant donor be started at the time of diagnosis. Delay after remission attainment that often occurs in identifying a suitable donor is a variable con- tributing to post-transplant relapse often not detailed in reports. More large studies such as this one are likely to improve outcomes as more markers of residual leukaemia are identified. Reference 1. Balsat M, Aline Renneville A, Thomas X, et al. J Clin Oncol DOI: 10.1200/JCO.2016.67.1875.

cal reports in the ASH 2016 plenary session, it is hard to choose one story for 2016. In- stead, I’m choosing to highlight a theme of growing importance – the increase in reports of minimal residual disease (MRD) assess- ment in AML. MRD in AML was the subject of several ASH presentations. I cite this recent Journal of Clinical Oncology study of many French centres that shows how the depth of cell kill after induction can potentially help doctors to estimate prognosis and make the decision about recommending transplant in first re- mission, somewhat akin to what has already happened in CML. 1 The study concerns patients with NPM1 mutations that occur in approximately 30% of AML and 60% of AML patients without

Dr Cunningham is Adjunct Associate Research Scientist in the Division of Hematology Oncology at Columbia University

College of Physicians and Surgeons, New York, and Associate Editor of the PracticeUpdate Oncology Editorial Board.

Monoclonal antibodies as therapeutic tools for myeloma By Rafael Fonseca, MD A lthough many new drugs have been approved in the last years as tools against

relapsed and refractory setting, and also the longest projected progression-free survival in any trial of myeloma that is relapsed or refractory. 3 Daratumumab is here to stay and is quickly gaining a foothold at the bedside. My colleague Dr Sagar Lonial pointed out a few years ago what he called “oncologic irony”; that is, that myeloma, the only disease that produces a monoclonal anti- body, had no available therapeu- tic monoclonal. The “oncologic irony” is finally over. References 1. Lonial S, Dimopoulos M, Palumbo A, et al. N Engl J Med 2015;373:621-631. 2. Palumbo A, Chanan-Khan A, Weisel K, et al. N Engl J Med 2016;375:754-766. 3. Dimopoulos MA, Oriol A, Nahi H, et al. N Engl J Med 2016;375:1319-1331.

now FDA- and TGA-approved and is being used in lenalido- mide-naive patients, including those with high-risk cytogenet- ics. Some questions remain, such as whether it will be useful in patients progressing on lenalid- omide maintenance or whether it will work in combination with pomalidomide. The second monoclonal anti- body approved is daratumumab, which targets the CD38 receptor in cells. While CD38 is not ex- clusively in myeloma cells, the antibody has shown evidence of anti-myeloma activity as a single agent. While this was impres- sive, the most notable results are those seen in the context of combinations with bortezomib and dexamethasone and also with lenalidomide and dexameth- asone. 2,3 The latter combination has now resulted in the clinical trial with the greatest rate of complete responses (43%) in the

myeloma, a whole new class of drugs has joined the toolbox: monoclonal antibodies. These antibodies have greatly aug- mented the capacity of myeloma doctors to control disease. First, elotuzumab is a monoclonal anti- body that targets the cell surface receptor SLAMF7 (previously known as CS1), which is mainly present in the surface of natural killer cells and myeloma cells. Elotuzumab alone has no direct anti-myeloma activity; but, when combined with lenalidomide and dexamethasone, it was associated with higher than anticipated re- sponse rates. This led to a phase 3 clinical trial that was published in 2016 wherein the three-drug combination demonstrated a superior outcome over lenalido- mide and dexamethasone alone (ELOQUENT-2). 1 This drug is

My colleague pointed out a few years ago what he called “oncologic irony”; that is, that myeloma, the only disease that produces a monoclonal antibody, had no available therapeutic monoclonal. The “oncologic irony” is finally over.

Dr Fonseca is a haematologist and Site Director of the

Hematologic Malignancies Program at the Mayo Clinic Cancer Center in Arizona.

PRACTICEUPDATE HAEMATOLOGY & ONCOLOGY