Das Medizinportal


Multiples Myelom – State of the art

Martin Schreder, Stefan Knop, Hermann Einsele; Würzburg (S. 10-14)


  1. Stewart AK et al. N Engl J Med 2015;372:142-52
  2. Dimopoulos MA et al. Lancet Oncol 2016;17:27-38
  3. Moreau P et al. N Engl J Med 2016;374:1621-34
  4. Richardson PG et al. Blood 2013;122:2331-7
  5. SanMiguel JF et al. Lancet Oncol 2014;15:1195-206
  6. Richardson PG et al. Blood 2016;127:713-21
  7. Lonial S et al. N Engl J Med 2015;373:621-31
  8. Krejcik J et al. ASH 2015, abstract #3037
  9. Lokhorst HM et al. N Engl J Med 2015;373:1207-19
  10. Lonial S et al. Lancet 2016:387;1551-60
  11. Usmani SZ et al. Blood 2016;128:37-44
  12. Palumbo A et al. EHA 2016; abstract #LB2236
  13. Dimopoulos MA et al. EHA 2016; abstract #LB2238
  14. Cavo M et al. ASCO 2016, abstract #8000
  15. Attal M et al. ASCO 2016, abstract #8001
  16. Sonneveld P et al. J Clin Oncol 2012;30:2946-55
  17. Mateos MV et al. J Clin Oncol 2010;28:2259-66
  18. Benboubker L et al. N Engl J Med 2014;371:906-17
  19. Palumbo A et al. Blood 2015; 125:2068-74
  20. Larocca A et al. Leukemia 2016; 30:1320-26

CLL – Update 2016

Till Seiler, Clemens-Martin Wendtner; München (S. 22-24)


  1. Goede V, Fischer K, Busch R, Engelke A, Eichhorst B, Wendtner CM, et al. Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. The New England journal of medicine. 2014;370(12):1101-10.
  2. International CLLIPIwg. An international prognostic index for patients with chronic lymphocytic leukaemia (CLL-IPI): a meta-analysis of individual patient data. The Lancet Oncology. 2016;17(6):779-90.
  3. Schweighofer C, Cymbalista F, Müller C, Busch R, Porcher R, Langerbeins P, et al. Early versus deferred treatment with combined fludarabine, cyclophosphamide and rituximab (FCR) improves event-free survival in patients with high-risk Binet stage A chronic lymphocytic leukemia – first results of a randomized German-French cooperative Phase III trial. Blood. 2013:abstract 524.
  4. Hallek M, Fischer K, Fingerle-Rowson G, Fink AM, Busch R, Mayer J, et al. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet. 2010;376(9747):1164-74.
  5. Fischer K, Bahlo J, Fink AM, Goede V, Herling CD, Cramer P, et al. Long-term remissions after FCR chemoimmunotherapy in previously untreated patients with CLL: updated results of the CLL8 trial. Blood. 2016;127(2):208-15.
  6. Fischer K, Cramer P, Busch R, Bottcher S, Bahlo J, Schubert J, et al. Bendamustine in combination with rituximab for previously untreated patients with chronic lymphocytic leukemia: a multicenter phase II trial of the German Chronic Lymphocytic Leukemia Study Group. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2012;30(26):3209-16.
  7. Eichhorst B, Fink AM, Bahlo J, Busch R, Kovacs G, Maurer C, et al. First-line chemoimmunotherapy with bendamustine and rituximab versus fludarabine, cyclophosphamide, and rituximab in patients with advanced chronic lymphocytic leukaemia (CLL10): an international, open-label, randomised, phase 3, non-inferiority trial. The Lancet Oncology. 2016.
  8. Goede V, Fischer K, Engelke A, Schlag R, Lepretre S, Montero LF, et al. Obinutuzumab as frontline treatment of chronic lymphocytic leukemia: updated results of the CLL11 study. Leukemia. 2015.
  9. Hillmen P, Robak T, Janssens A, Govindbabu K, Grosicki S, Mayer J, et al. Ofatumumab + Chlorambucil Versus Chlorambucil Alone In Patients With Untreated Chronic Lymphocytic Leukemia (CLL): Results Of The Phase III Study Complement 1 (OMB110911). Blood. 2013:Abstract 528.
  10. Byrd JC, Furman RR, Coutre SE, Flinn IW, Burger JA, Blum KA, et al. Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. The New England journal of medicine. 2013;369(1):32-42.
  11. Byrd JC, Brown JR, O'Brien S, Barrientos JC, Kay NE, Reddy NM, et al. Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. The New England journal of medicine. 2014;371(3):213-23.
  12. Burger JA, Tedeschi A, Barr PM, Robak T, Owen C, Ghia P, et al. Ibrutinib as Initial Therapy for Patients with Chronic Lymphocytic Leukemia. The New England journal of medicine. 2015;373(25):2425-37.
  13. Farooqui MZ, Valdez J, Martyr S, Aue G, Saba N, Niemann CU, et al. Ibrutinib for previously untreated and relapsed or refractory chronic lymphocytic leukaemia with TP53 aberrations: a phase 2, single-arm trial. The Lancet Oncology. 2015;16(2):169-76.
  14. Furman RR, Sharman JP, Coutre SE, Cheson BD, Pagel JM, Hillmen P, et al. Idelalisib and rituximab in relapsed chronic lymphocytic leukemia. The New England journal of medicine. 2014;370(11):997-1007.
  15. Roberts AW, Davids MS, Pagel JM, Kahl BS, Puvvada SD, Gerecitano JF, et al. Targeting BCL2 with Venetoclax in Relapsed Chronic Lymphocytic Leukemia. The New England journal of medicine. 2016;374(4):311-22.
  16. Stilgenbauer S, Eichhorst B, Schetelig J, Coutre S, Seymour JF, Munir T, et al. Venetoclax in relapsed or refractory chronic lymphocytic leukaemia with 17p deletion: a multicentre, open-label, phase 2 study. The Lancet Oncology. 2016;17(6):768-78.

Follikuläres Lymphom – Diagnostik und Therapie

Alexander Grunenberg, Christian Buske; Ulm (S. 26-28)


  1. Smith, A., et al., Lymphoma incidence, survival and prevalence 2004-2014: sub-type analyses from the UK's Haematological Malignancy Research Network. Br J Cancer, 2015. 112(9): p. 1575-84.
  2. Nogai, H., B. Dörken, and G. Lenz, Pathogenesis of non-Hodgkin's lymphoma. J Clin Oncol, 2011. 29(14): p. 1803-11.
  3. Weigert, O. and D.M. Weinstock, The evolving contribution of hematopoietic progenitor cells to lymphomagenesis. Blood, 2012. 120(13): p. 2553-61.
  4. Dreyling, M., et al., Newly diagnosed and relapsed follicular lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol, 2014. 25 Suppl 3: p. iii76-82.
  5. Friedberg, J.W., et al., Effectiveness of first-line management strategies for stage I follicular lymphoma: analysis of the National LymphoCare Study. J Clin Oncol, 2012. 30(27): p. 3368-75.
  6. Dupuis, J., et al., Impact of [(18)F]fluorodeoxyglucose positron emission tomography response evaluation in patients with high-tumor burden follicular lymphoma treated with immunochemotherapy: a prospective study from the Groupe d'Etudes des Lymphomes de l'Adulte and GOELAMS. J Clin Oncol, 2012. 30(35): p. 4317-22.
  7. Luminari, S., et al., The use of FDG-PET in the initial staging of 142 patients with follicular lymphoma: a retrospective study from the FOLL05 randomized trial of the Fondazione Italiana Linfomi. Ann Oncol, 2013. 24(8): p. 2108-12.
  8. Solal-Celigny, P., et al., Follicular lymphoma international prognostic index. Blood, 2004. 104(5): p. 1258-65.
  9. Federico, M., et al., Follicular lymphoma international prognostic index 2: a new prognostic index for follicular lymphoma developed by the international follicular lymphoma prognostic factor project. J Clin Oncol, 2009. 27(27): p. 4555-62.
  10. Pastore, A., et al., Integration of gene mutations in risk prognostication for patients receiving first-line immunochemotherapy for follicular lymphoma: a retrospective analysis of a prospective clinical trial and validation in a population-based registry. Lancet Oncol, 2015. 16(9): p. 1111-22.
  11. Wilder, R.B., et al., Long-term results with radiotherapy for Stage I-II follicular lymphomas. Int J Radiat Oncol Biol Phys, 2001. 51(5): p. 1219-27.
  12. Ardeshna, K.M., et al., Rituximab versus a watch-and-wait approach in patients with advanced-stage, asymptomatic, non-bulky follicular lymphoma: an open-label randomised phase 3 trial. Lancet Oncol, 2014. 15(4): p. 424-35.
  13. Rummel, M.J., et al., Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial. Lancet, 2013. 381(9873): p. 1203-10.
  14. Flinn, I.W., et al., Randomized trial of bendamustine-rituximab or R-CHOP/R-CVP in first-line treatment of indolent NHL or MCL: the BRIGHT study. Blood, 2014. 123(19): p. 2944-52.
  15. Salles, G., et al., Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial. Lancet, 2011. 377(9759): p. 42-51.
  16. Fowler, N.H., et al., Safety and activity of lenalidomide and rituximab in untreated indolent lymphoma: an open-label, phase 2 trial. Lancet Oncol, 2014. 15(12): p. 1311-8.
  17. Salles, G.A., et al., Obinutuzumab (GA101) in patients with relapsed/refractory indolent non-Hodgkin lymphoma: results from the phase II GAUGUIN study. J Clin Oncol, 2013. 31(23): p. 2920-6.
  18. Gopal, A.K., et al., PI3Kdelta inhibition by idelalisib in patients with relapsed indolent lymphoma. N Engl J Med, 2014. 370(11): p. 1008-18.
  19. Lesokhin, A.M., et al., Nivolumab in Patients With Relapsed or Refractory Hematologic Malignancy: Preliminary Results of a Phase Ib Study. J Clin Oncol, 2016.
  20. Cang, S., et al., ABT-199 (venetoclax) and BCL-2 inhibitors in clinical development. J Hematol Oncol, 2015. 8: p. 129.


Claudia Schwarzenberger (S. 40)


  1. Stephens PJ et al.: Massive Genomic Rearrangement Acquired in a Single Catastrophic Event during Cancer Development. Cell 2011 Jan 7; 144(1):27-40
  2. Hatch et al. Catastrophic nuclear envelope collapse in cancer cell micronuclei. Cell 2013 Jul 3; 154(1):47–60
  3. Terradas et al. Impaired nuclear functions in micronuclei results in genome instability and chromothripsis. Arch Toxicol 2016 Aug 19; doi:10.1007/s00204-016-1818-4 [Epub ahead of print]
  4. Rausch T et al.: Genome Sequencing of Pediatric Medulloblastoma Links Catastrophic DNA Rearrangements with TP53 Mutations. Cell. 2012 Jan 20; 148(1-2): 59–71
  5. McEvoy J et al.: RB1 gene inactivation by chromothripsis in human retinoblastoma. Oncotarget 2014 Jan; 5(2): 438–450
  6. Kovtun et al. Chromosomal catastrophe is a frequent event in clinically insignificant prostate cancer. Oncotarget 2015 Oct 6; 6(30):29087–96
  7. Kloosterman W and Cuppen E: Chromothripsis in Congenital Disorders and Cancer: Similarities and Differences. Curr Opin Cell Biol 2013 Jun; 25(3):341–8
  8. de Pagter et al. Chromothripsis in healthy individuals affects multiple protein-coding genes and can result in severe congenital abnormalities in offspring. Am J Hum Genet 2015 Apr 2; 96(4):651–6
  9. Hatch E and Hetzer M. Quick guide: Chromothripsis. Cell Press Curr Biol 2015, May 18; 25, R391–99


Claudia Schwarzenberger (S. 42-43)


  1. Kehoe S et al. Primary chemotherapy versus primary surgery for newly diagnosed advanced ovarian cancer (CHORUS): an open-label, randomised, controlled, non-inferiority trial. The Lancet 2015 Jul 18, 386, No. 9990, p249–257
  2. Ionnides CG et al. Tumor Cytolysis by Lymphocytes Infiltrating Ovarian Malignant Ascites. Cancer Res 1991; 51:4257–65
  3. Kooi S et al. HLA class I expression on human ovarian carcinoma cells correlates with T-cell infiltration in vivo and T-cell expansion in vitro in low concentrations of recombinant interleukin-2. Cell Immunol 1996 Dec 15; 174(2):116–28
  4. Vacchelli E et al. Trial Watch: Chemotherapy with immunogenic cell death inducers. Oncoimmunology 2014; 3:e27878
  5. Menger L et al. Cardiac glycosides exert anticancer effects by inducing immunogenic cell death. Sci Transl Med 2012; 4:143ra99
  6. Michaud M et al. Autophagy-dependent anticancer immune responses induced by chemotherapeutic agents in mice. Science 2011; 334:1573–7

Der ältere Patient: Krebs-Früherkennung

Friederike Klein (S. 54-55)


  1. Schonberg M et al. J Am Geriatr Soc 2015; 63: 750-6
  2. Altenhofen L et al./ZI: 12. Jahresbericht zu Früherkennungs-Koloskopien 2014, erschienen Januar 2016
  3. Drazer MW et al. Cancer 214, 120: 1491-8
  4. Royce TJ et al. JAMA Intern Med 2014; 174: 1558-1565
  5. Sima CS et al. JAMA 2010; 304: 1584–91
  6. Guo F et al. Prev. Med 2015; 81: 427-32
  7. www.g-ba.de/downloads/62-492-1205/KFE-RL_2015-10-15_iK-2016-07-01.pdf 
  8. Royce TJ et al. JAMA Intern Med 2014; 174: 1558-1565
  9. AGS Choosing Wisely Workgroup. J Am Geriatr Soc 2014; 62: 950-60
  10. Pollack CE et al. JAGS 64:1032–1038, 2016
  11. Schonberg MA et al. J Am Geriatr Soc 2011; 59: 1444-51

Pharmaforum: BRAF-mutiertes mCRC: Bevacizumab/FOLFOXIRI effektiv und verträglich

Roche (S. 59)

  1. Cremolini C et al., Lancet Oncol 2015, 16:1306–1315 

Pharmaforum: ESMO Guidelines

Roche (S.60)


  1. Van Cutsem E et al. Ann Oncol 2016; 27(8): 1386-1422. doi:10.1093/annonc/mdw235
  2. Ferlay J et al. Eur J Cancer 2013; 49: 1374-1403. 
  3. Ferlay J et al. Int J Cancer 2015; 136: E359-E386. 
  4. Van Cutsem E et al. Ann Oncol 2014; 25(Suppl 3): iii1-iii9. 
  5. Hurwitz H et al. N Engl J Med 2004; 350: 2335-2342. 
  6. Saltz LB et al. J Clin Oncol 2008; 26: 2013-2019. 
  7. Lenz HJ et al. Ann Oncol 2014; 25(Suppl 5): abstr 501O. 
  8. Heinemann V et al. Lancet Oncol 2014; 15: 1065-1075. 
  9. Fachinformation Avastin®, Stand Juni 2016. 
  10. Cunningham D et al. Lancet Oncol 2013; 14: 1077-1085. 
  11. Kabbinavar F et al. Oncology 2008; 75: 215-223. 
  12. Tebbutt NC et al. J Clin Oncol 2010; 28: 3191-3198. 
  13. de Gramont A et al. J Clin Oncol 2000; 18: 2938-2947. 
  14. Douillard JY, Group VS. Oncology 2000; 14: 51-55. 
  15. Folprecht G et al. Ann Oncol 2014; 25: 1018-1025. 
  16. Loupakis F et al. N Engl J Med 2014; 371: 1609-1618. 
  17. Cremolini C et al. Lancet Oncol 2015; 16: 1306-1315.

Pharmaservice: Highlights aus der Hämatologie

Claudia Schwarzenberger (S.62)


  1. Smith CC, Shah NP. Tyrosine kinase inhibitor therapy for chronic myeloid leukemia: approach to patients with treatment-naive or refractory chronic-phase disease
  2. Hughes TP, Cercantes F, Spector N et al.: Treatment-Free Remission (TFR) Eligibility in Patients (pts) with Chronic Myeloid Leukemia in Chronic Phase (CML-CP) and Residual Disease on Long-Term Imatinib (IM) Who Switched to Second-Line Nilotinib (NIL). ASH Annual Meeting 2015, Orlando, Florida, 5. - 8. Dezember 2015; Abstract 4029
  3. Hochaus A, Saglio G, Hughes TP et al.: Impact of Treatment with Frontline Nilotinib (NIL) vs Imatinib (IM) on Sustained Deep Molecular Response (MR) in Patients (pts) with Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase (CML-CP). ASH Annual Meeting 2015, Orlando, Florida, 5. - 8. Dezember 2015; Abstract 2781
  4. Hochhaus A, Masszi T, Giles FJ et al.: Treatment-free remission (TFR) in patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP) treated with frontline nilotinib: Results from the ENESTfreedom study. American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, IL, USA, June 3-7, 2016; Abstract #7001.
  5. Richter J, Mahon F, Guilhot J et al.: Stopping Tyrosine Kinase Inhibitors in a very large cohort of european chronic myeloid leukemia patients: results of the EURO-SKI-Trial. 21st Congress of the European Hematology Association
  6. (EHA), Copenhagen, Denmark, June 9-12, 2016; Abstract S145
  7. Hughes HP, Boquimpani C, Ki DK et al: Treatment-free remission (TFR) in patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP) treated with second-line nilotinib (NIL): First results from the ENESTop study. American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, IL, USA, June 3-7, 2016; Abstract #7054