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Annals of Oncology
potent anti-angiogenic properties. Evidence now indicates that clinical benefit can be
gained in thalidomide-treated and refractory patients. In this respect cereblon has
been identified as an intracellular imid binding moiety which is responsible for the
teratogenic effects of these agents loss of which can mediate resistance to imids.It is
possible to build combinations which improve the activity of Imid drugs.
Co-administration of dexamethasone may synergistically improve the tumoricidal
effects of lenalidomide but during maintenance the inhibition of the
immune-enhancing effect of lenalidomide may impair its activity. There are a number
of antibodies, including elotuzomab, which may be combined with lenalidomide. In
view of the effects of lenalidomide on the epigenetic upregulation of tumour suppressor
genes combination with other epigenetic agents such as HDAC inhibitors and
demethylating agents may be useful. As research continues, additional insights into the
mechanism of action of Imid drugs which may help to further maximize the use of
lenalidomide and subsequently pomalidomide in the treatment of MM.
Disclosures: All authors have declared no conflicts of interest.
68IN TARGETED THERAPY IN MALIGNANT LYMPHOMA: CLINICAL
IMPLICATIONS AND PERSPECTIVES
M. Ghielmini
Medical Oncology, IOSI Istituto Oncologico Svizzera Italiana Ospedale Regionale
Bellinzona e Valli, Bellinzona, SWITZERLAND
With a whole range of new drugs showing activity in different types of
lymphoma, we question if any of these will make the new step forward as it has
been the case with the introduction of doxorubicin, high-dose chemotherapy or
rituximab. If we look at some most significant diseases, we can hope that for
Hodgkin’s lymphoma (HL) the advent of active drugs as brentixumab vedotin
and panobinostat could make chemotherapy more effective, reducing the number
of cycles needed or allowing the avoidance of drugs with long-term side effects.
In the treatment of diffuse large B-cell lymphoma (DLBCL) what is needed is a
drug improving on the cure rate. The new available substances have not yet
shown to be so promising but not all of them have yet been combined with
classical chemotherapy. Follicular lymphoma (FL) is a well controllable disease
but we want a drug which will render this disease curable; in the meanwhile we
hope that patient-friendly treatments will allow long-term maintenance and
disease control. The combination of lenalidomide with rituximab, but also the
new CAL 101, BTK inhibitors or inotuzumab ozogamicin could increase the
possibility of prolonging the time without symptoms of disease or treatment. The
impact of these drugs on survival though will be long to ascertain in such an
indolent disease. Mantle cell lymphoma (MCL) remains rapidly progressing and
difficult to treat. It is considered not curable and it will therefore be important
ascertain the impact of bortezomib, temsirolimus, BTK and PI3K inhibitors or
blinotumumab combined with standard treatment on survival or cure. Finally,
peripheral T-cell lymphoma (PTCL) is an orphan disease compared to the B-cell
lymphomas as it could not take advantage of the introduction of rituximab. In
anaplastic large cell lymphoma (ALCL) brentuximab vedotin has shown very
important activity and might make the difference, while the addition of
pralatrexate, romidepsin or vorinostat could change the prognosis of the other
entities. Despite many of these drugs having shown promising data, the challenge
is now to combine them with standard treatment in order to obtain regimens
which are more active but not more toxic. Phase II trials are ongoing to develop
the optimal combination schedules.
Disclosure: M. Ghielmini: Member of advisory board for Roche, Lilly, BMS, Celgene,
Pfizer, Jansen
Volume 23 | Supplement 9 | September 2012 doi:10.1093/annonc/mds382 | ix45