memo - Magazine of European Medical Oncology

Zojer, Niklas

2015 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-015-0199-3

2015 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-015-0208-6

Gunsilius, Eberhard

2015 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-015-0204-x

Zojer, Niklas; Ludwig, Heinz

2015 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-015-0207-7

Cytogenetic data have established relevance for prognostication in myeloma. Also, certain chromosomal aberrations were associated with an increased risk of progression of smoldering myeloma to active disease. The impact of cytogenetic and molecular data on treatment decisions is however limited. Myeloma patients with a t(4;14) have been shown to benefit from bortezomib treatment, while thalidomide treatment has a detrimental effect in cases with del17p13. The discovery of marked intraclonal heterogeneity has influence on therapeutic concepts to treat plasma cell disease, but so far no relevance for guiding treatment in individual cases. Cereblon is the molecular target of immunomodulatory substances, and expression levels have been linked to treatment outcome under thalidomide, lenalidomide, and pomalidomide treatment. Alternative splicing has been described for cereblon, and relevance of different isoforms for drug sensitivity is currently under study. So far no reliable clinical test exists to predict for response to immunomodulatory substances.

Ludwig, Heinz; Hilbe, Wolfgang; Zojer, Niklas

2015 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-014-0194-0

This minireview covers novel drugs and treatment concepts being evaluated in early studies for therapy of patients with multiple myeloma (MM). Panobinostat, a histone deacetylase inhibitor, showed limited improvement in progression-free survival, thus raising doubt whether these substances will provide clinical meaningful benefits in MM. Some of the new proteasome inhibitors beyond carfilzomib offer the benefit of oral administration and reduced neurotoxicity. Monoclonal antibodies with antimyeloma or antistroma cell activity raise expectations for improved treatment outcome when combined with conventional chemotherapy. A series of new inhibitors of signal pathways important for proliferation and progression in MM presently are scrutinized for their clinical usefulness. Among these, inhibitors of the mitogen activated protein kinase (MAPK), epidermal growth factor receptor (EGFR), protein kinase B (AKT), and B-cell receptor pathway as well as drugs inhibiting the spindle protein, Bcl-2, and cyclin-dependent kinases show promise for becoming important antimyeloma dugs. Checkpoint inhibitors have shown significant activity in some solid tumors and are now tested in MM as well. Measles viruses bind via CD46 to myeloma cells, self-amplify at sites of tumor growth, and induce cell death in myeloma but not in normal cells, thus offering a completely new treatment strategy. However, before introduction of these interesting approaches into the clinic, confirmation of their clinical efficacy is needed.

Fillitz, Michael; Seebacher, Adelheid; Panny, Michael

2015 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-015-0206-8

During the course of disease multiple myeloma subclones acquire more and more additional genetic changes causing an aggressive proliferative growth with less responsiveness to therapeutic agents. On the other hand new therapeutic options are getting available, leading to the question, if a more intensive treatment in newly diagnosed myeloma patients may result in a better outcome concerning progression-free survival, quality of life and overall survival. In newly diagnosed myeloma patients, physicians have to distinguish between patients eligible for autologous stem cell transplantion (ASCT) and patients ineligible for ASCT. Transplant eligibility is mainly based on biological age, performance status and co-morbidities. New data suggest that prolonged treatment—synonymously called maintenance therapy—may lead to additional survival benefit even in the elderly/frail patient group. Yet there is no clear data on overall survival for prolonged treatment. At time the first-line armoury in myeloma consists of chemotherapy, steroids, proteasome inhibitors and immunmodulatory/antiangiogenetic drugs. The role of new antibodies in myeloma treatment is evolving but there is only limited (but promising) data available yet. New agents might reduce the therapeutic side-effects of an intensive treatment despite increasing efficacy as shown, e.g., for the new proteasome inhibitor carfilzomib. In the first-line setting, other new oral proteasome inhibitors with low dose-limiting neurotoxicity rates will be available shortly. In this short review, therapeutic strategies will be discussed focusing on treatment intensity.

Lechner, Daniel

2015 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-014-0193-1

Renal impairment is a common phenomenon in myeloma patients. Pathogenesis is mainly based on the presence of monoclonal paraprotein but may include myeloma-independent mechanisms as well. There are various forms of paraprotein-related renal impairment. The majority of severe cases are due to cast nephropathy where precipitation on the basis of monoclonal free light chains causes complex tubular damage. Cast nephropathy requires quick diagnosis and specific treatment. Renal impairment increases mortality in myeloma patients. A quick and sustained response to treatment is crucial for preventing long-term dialysis dependence. Apart from preventing or treating other conditions endangering kidney function, an effective antimyeloma treatment is the mainstay of therapy. Available data are limited but novel substances added considerable efficacy to preexisting treatment concepts. Bortezomib gained importance due to its rapid action and missing nephrotoxicity, but also immunmodulatory substances such as lenalidomide were shown to restore kidney function. Cytostatic substances such as cyclophosphamide, bendamustine, and doxorubicin remain valuable combination partners for novel substances in order to achieve significant tumor responses. Extracorporeal removal of free light chains by plasmapheresis or extended daily high cut-off hemodialysis, if available, may further optimize management of acute myeloma-related renal failure.

Zojer, Niklas; Gschwantler, Michael; Hilbe, Wolfgang

2015 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-015-0198-4

We report on a patient with multiple myeloma and light-chain induced renal failure, diagnosed with hepatitis C and high viral load in the pre-transplant period. We show that the new hepatitis C virus directed drugs daclatasvir and sofosbuvir can be safely applied concomitantly to high-dose therapy with autologous hematopoietic stem cell transplantation. Liver enzymes remained in the normal range during the transplant and in the post-transplant period.

Fridrik, Michael A.

2015 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-015-0200-1

Double hit (DH) are defined as MYC and BCL2 or/and BCL6 coexpressing B-cell lymphomas. Morphologically they are found in the diffuse large B-cell lymphoma (DLBCL) or in the group of B-cell lymphoma, unclassifiable, with features between DLBCL and Burkitt lymphoma (BCLU). Approximately 5–10 % of DLBCLs and BCLUs are DH lymphomas according to fluorescence in situ hybridization, the percentage rises to 30 %, if protein overexpression is detected by immunohistochemistry. Treatment with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone seems to be insufficient. However, for more intensive regimens and/or high-dose therapy with stem cell rescue conflicting results exist. Clinical trials with novel therapies are urgently needed.

Vrdoljak, Eduard; Boraska Jelavić, Tihana; Petrić Miše, Branka

2015 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-015-0202-z

Gynecological malignancies account round 10 % of all female cancers, with the uterine cancer being the most predominant one. Surveillance programs of all gynecologic cancers are primarily based on recurrence rates, timing of recurrence, salvage options and chances for cure of patient with recurrence. Since there is no prospective, high evidence data about optimal surveillance program after primary treatment of patients with endometrial cancer recommendations are based on review of retrospective data sets. From all the diagnostic tools available, history taking and clinical examination, including comprehensive gynecological examination, still contribute to the greatest number of recurrence detection. Radiologic tests are usually employed when a suspicion of recurrence is raised. Follow-up plan should be tailored according to the estimated risk of relapse for individual patient.

Vrdoljak, Eduard; Boraska Jelavić, Tihana; Petrić Miše, Branka; Omrčen, Tomislav

2015 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-015-0203-y

Gynecological malignancies account for round 10 % of all female cancers, with the cervical cancer being one of the major women health problems in developing regions of the world. Surveillance programs of cervical cancer are primarily based on recurrence rates, timing of recurrence, salvage options, and chances for curing patients with recurrence. Since there is no prospective, high evidence data about optimal surveillance program after primary treatment of patients with cervical cancer recommendations are based on the review of retrospective data sets. Literature search on this topic showed that there is no proven survival benefit for any follow-up schedule. Counseling the patients about early possible signs and symptoms of recurrent disease is of great importance. From all the diagnostic tools available, history taking and clinical examination, including comprehensive gynecological examination, still contribute to the greatest number of recurrence detection. Chest radiograph and computed tomography of abdomen and pelvis could be done in high-risk patients taking into account initial stage of the disease, previous treatment, symptom status, and local findings in order to detect potentially salvageable recurrences. Otherwise, radiologic tests are usually employed when a suspicion of recurrence is raised. Follow-up plan should be tailored according to estimated risk of relapse for individual patient.

Amann, Arno; Gamerith, Gabriele; Huber, Julia M.; Zwierzina, Marit; Hilbe, Wolfgang; Zwierzina, Heinz

2015 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-015-0196-6

Because of recent failures of novel drugs in phase II and III trials innovative in vitro models are needed that may predict drug efficacy in patients. Although, numerous modifications of traditional cell culture and animal models were undertaken significant improvements in cell culture- based drug development have not been achieved. Three-dimensional (3D) cell culture may represents an modern alternative to bridge the gap between 2D cell cultures and animal models.