January 26-28, 2017, San Francisco (CA), USA
Fatime Krasniqi and Emanuele Zucca
Brentuximab Vedotin (BV) appears to become the standard in patients with r/r CD30-expressing cu-taneous T-cell lymphoma: Results of the Phase 3 ALCANZA study
The ALCANZA study is a randomized, open-label, mul-ticenter phase 3 trial testing the efficacy and safety of BV vs physician’s choice (PC) of methotrexate (MTX) or bex-arotene (Bex), in previously treated patients with CD30-expressing CTCL [3]. In this study 131 patients were included and randomized; baseline characteristics were generally balanced between arms with the exception of more patients with extracutaneous disease in the BV arm.
Table 1. Main novel PTCL variants and entities.
Anaplastic large cell lymphoma (ALCL) – ALK‐negative ALCL (definite entity)
– Breast-implant-associated ALCL (new provisional entity)
Nodal TCL with TFH-phenotype – AITL
– Follicular T-cell lymphoma (FTCL) – Other nodal PTCL with TFH phenotype Enteropathy-associated TCL (EATL) – Type 1, celiac disease associated
Monomorphic epitheliotropic intestinal TCL (MEITL) Indolent T-cell LPD of the GI-tract
Systemic EBV+ T-cell lymphoma of childhood Cutaneous T-cell LPD
– Variants (LyP) and provisional entities T-cell LGL
– STAT3 & STAT5B mutations
modified by Stefan Dirnhofer
KONGRESSBERICHT
At a median follow-up of 22.9 months, ORR4 (primary endpoint) and PFS strongly favored BV vs PC with an ORR4 of 56% vs 13% (p<0.0001) and a median PFS of 16.7 vs 3.5 months (HR 0.270; 95% CI, 0.169–0.430;
p<0.0001), respectively [3]. ORR was 67% (n=43) with CR 16% for BV, compared with an ORR of 20% (n=13) with CR 2% for PC (ORR, p<0.0001; CR, p=0.0046), with a similar side-effect profile [3]. These data show a sta-tistically significant superiority of BV therapy compared to PC of Bex or MTX in CD30+ CTCL.
New combinations with CHOP backbone in PTCLs:
Strengths and limitations
The standard therapy for PTCL is still based on anthra-cycline-containing chemotherapy such as CHOP (cyclo-phosphamide, doxorubicin, vincristine, and prednisolone) or CHOP-like regimens, although the outcome is not sa- tisfactory [4]. Even more intensive treatment regimens did not improve outcome. As an alternative approach, the combination of CHOP with new agents which have dif-ferent mechanisms of action and therapeutic targets has been tried in several clinical trials, including the anti-CD52 monoclonal antibody (alemtuzumab), proteasome
inhibitor (bortezomib), anti-vascular endothelial growth factor antibody (bevacizumab), denileukin diftitox, and mTOR inhibitor (everolimus) [5-10].
Several small phase 2 studies have suggested a potential benefit of the addition of new agents (such as alemtuzum-ab, bortezomib, bevacizumalemtuzum-ab, everolimus, demileukin) to the CHOP backbone especially regarding the response rate. However, relatively short duration of response and the occurrence of significant toxicities, such as infection, limited the value of those combinations [10]. Currently, phase 3 trials adding other agents to the CHOP backbone are ongoing, such as the histone deacetylase inhibitor, ro-midepsin, and the anti-CD30 monoclonal antibody, bren-tuximab vedotin [10]. The results of phase 3 studies might provide more strong information regarding the efficacy of the therapeutic strategy based on adding new agents to the CHOP backbone [10].
New single agents on the horizon of PTCL treatment To improve the outcome of patients with PTCL, the in-troduction of novel agents is necessary. Recent research has led to the development of numerous agents, including HDAC inhibitors, immunconjugates, antifolates, mono-Table 2. Novel single agents.
modified by Barbara Pro
clonal antibodies, immunmodulatory agents, nucleoside analogs, proteasome inhibitors, kinase inhibitors, benda-mustine and other targeted therapies [11]. However, a number of other agents in use or under investigation have also shown promising activity as shown in Table 2 [12].
Some of them are exploring very new strategies, for exam-ple, MRG-106, a synthetic inhibitor of microRNA-155.
This compound is being tested in patients with CTCLs.
Six patients with confirmed MF diagnosis, clinical stage I-III with plaques or tumors, were included. All patients showed a reduction in the baseline Composite Assessment of Index Lesion Severity (CAILS) score [13]. These pre-liminary results are encouraging for MRG-106 as a novel therapeutic approach for MF. The trial is ongoing and ad-ditional results will be presented as available [13]. Other novel therapeutic agents, such as immune checkpoint in-hibitors, ruxolitinib (which acts on the JAK/STAT path-way), MK2006 (an AKT inhibtor), alefacept (an immun-suppressive dimeric fusion protein), and pembrolizumab (a PD-1 antibody are also being investigated in clinical trials) [11, 12].
Conclusive remarks
The 9th T-cell Lymphoma Forum was the last of a series of succesful annual scientific meetings, and provided an in-teresting platform for scientists and clinicans from around the world to come together, share updates and discuss the latest findings related to the biology of T-cell lymphomas as well as their current and future treatment.
References:
1. Gaulard P, de Leval L. TCL-Forum 2017.
2. de Leval L, Gaulard P. TCL-Forum 2017.
3. Kim Y, Whittaker S, Horwitz S, et al. TCL-Forum 2017.
KONGRESSBERICHT
4. Briski R, Feldman AL, Bailey NG, et al. The role of front-line anthracycline-containing chemotherapy regimens in peripheral T-cell lymphomas. Blood Cancer J 4: e214, 2014.
5. Kluin-Nelemans HC, van Marwijk Kooy M, Lugtenburg PJ, et al. Intensified alemtuzumab-CHOP therapy for peripheral T-cell lymphoma. Ann Oncol 22: 1595-1600, 2011.
6. Kim SJ, Yoon DH, Kang HJ, et al. and Consortium for Improving Survival of Lymphoma. Bortezomib in combination with CHOP as first-line treatment for patients with stage III/IV peripheral T-cell lymphomas: a multicentre, single-arm, phase 2 trial. Eur J Cancer 48: 3223-3231, 2012.
7. Ganjoo K, Hong F, Horning SJ, et al. Bevacizumab and cy-closphosphamide, doxorubicin, vincristine and prednisone in combination for patients with peripheral T-cell or natural killer cell neoplasms: an Eastern Cooperative Oncology Group study (E2404). Leuk Lymphoma 55: 768-772, 2014.
8. Foss FM, Sjak-Shie N, Goy A, et al. A multicenter phase II trial to determine the safety and efficacy of combination therapy with denileukin diftitox and cyclophosphamide, doxorubicin, vincris-tine and prednisone in untreated peripheral T-cell lymphoma: the CONCEPT study. Leuk Lymphoma 54: 1373-1379, 2013.
9. Kim SJ, Shin DY, Kim JS, et al. A phase II study of everolimus (RAD001), an mTOR inhibitor plus CHOP for newly diagnosed peripheral T-cell lymphomas. Ann Oncol 27: 712-718, 2016.
10. Seok-Jin K. TCL-Forum 2017.
11. Zhang Y et al. Therapeutic options in peripheral T cell lympho-ma. J Hematol Oncol 9: 37, 2016.
12. Pro B. TCL-Forum 2017.
13. Querfeld C, et al. TCL-Forum 2017.
Correspondence:
Dr. Fatime Krasniqi University Hospital Basel Petersgraben 4, CH-4031 Basel fatime.krasniqi@usb.ch
AGENDA
2017
01.09. SAKK Orphan Malignancies Seminar 2017 Zürich, CH www.sakk.ch
07.-08.09. 20. Internationales Seminar «Onkologische Pflege – Fortgeschrittene Praxis»
St. Gallen, CH St. Gallen Oncology Conferences (SONK)
Deutschsprachig-Europäische Schule für Onkologie (deso) deso@oncoconferences.ch, www.oncoconferences.ch
08.09. 8ème Journée Romande de Soins en Oncologie Suisse Lausanne, CH www.soinsoncologiesuisse.ch
29.09.-03.10. Jahrestagung der Deutschen, Österreichischen und Schweizerischen Gesellschaften Stuttgart, D für Hämatologie und Medizinische Onkologie
ICS Internationales Congresscenter Stuttgart, www.haematologie-onkologie-2017.com 10/2017 Master Online Studiengang Advanced Oncology
Master of Science (MSc), Lehrsprache Englisch, berufsbegleitend, online – 60 ECTS Punkte Studienbeginn 10/2017 – Dauer 4 Semester – Kontakt: masteroncology@uni-ulm.de
06.-07.10. Eastern Europe and Balkan Region Refresher Course on Breast Cancer Krakow, PO European School of Oncology, Piazza Indipendenza 2, CH-6500 Bellinzona
lrichetti@eso.net, www.eso.net
18.-20.10. 4th Masterclass in Clinical Oncology
Tbilisi, GE European School of Oncology, Via Turati 29, I-20121 Milan dmengato@eso.net, www.eso.net
19.-21.10. Stop Cancer Now! Cancer and Global Health: From Research to Policy Lugano, CH European School of Oncology, Piazza Indipendenza 2, CH-6500 Bellinzona
azampetti@eso.net, www.eso.net
24.10. Anlassreihe Cancer Academy 2017: Brustkrebs
Zürich, CH Prof. Dr. med. Daniel Fink, Leiter Brustkrebszentrum und Mitarbeitende Aula der Universität Zürich, Rämistrasse 71, CH-8006 Zürich
Kostenlose Anmeldung unter www.cancercenter.usz.ch/Anmeldung-Cancer-Academy oder cancercenter@usz.ch 27.-28.10. 6. Symposium Integrative Onkologie und Forschung
St. Gallen, CH Schwerpunktthema Fasten und Ernährung bei Krebs
Weitere Informationen: ermina.zecic@kssg.ch, www.integrative-oncology.ch 27.-28.10. 9th Clinical Oncology Update – Onkologia 2017
Krakow, PL European School of Oncology, Piazza Indipendenza 2, CH-6500 Bellinzona eso@eso.net, www.eso.net
02.-04.11. ESO-ESMO Advanced Breast Cancer Fourth International Consensus Conference (ABC4) Lisbon, PT European School of Oncology, Via Turati 29, I-20121 Milan
fmarangoni@eso.net, www.eso.net
04.-07.11. 20th International Meeting of the European Society of Gynaecological Oncology (ESGO) Vienna, AT www.esgo.org
09.11. 7. Interdisziplinäres Prostatakarzinomsymposium St. Gallen, CH St. Gallen Oncology Conferences (SONK)
info@oncoconferences.ch, www.oncoconferences.ch/pro 23.-24.11. SAKK Semi-Annual Meeting
Zürich, CH www.sakk.ch
28.11. Anlassreihe Cancer Academy 2017: Hirntumoren
Zürich, CH Prof. Dr. med. Michael Weller, Leiter Hirntumorzentrum und Mitarbeitende Aula der Universität Zürich, Rämistrasse 71, CH-8006 Zürich
Kostenlose Anmeldung unter www.cancercenter.usz.ch/Anmeldung-Cancer-Academy oder cancercenter@usz.ch
2018
26.-28.01. LYFE – Lymphoma Forum of Excellence: «What’s new in lymphoid neoplasias?»
Bellinzona, CH Oncology Institute of Southern Switzerland (IOSI), Ospedale San Giovanni, CH-6500 Bellinzona info@lymphomaforum.ch, www.lymphomaforum.ch
15.-17.03. 4th St. Gallen International Gastrointestinal Cancer Conference (GICC 2018) St. Gallen, CH Under the auspices of EORTC
St. Gallen Oncology Conferences (SONK) info@oncoconferences.ch, www.oncoconferences.ch/gicc
28.09.-02.10. Jahrestagung der Deutschen, Österreichischen und Schweizerischen Gesellschaften Wien, AT für Hämatologie und Medizinische Onkologie