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New agents for the treatment of lymphoid leukemia and lymphoma: Focus on Recent FDA Approvals

DISCOVERIES (ISSN 2359-7232), 2014, January-March

CITATION:

Stancu AL, Smith MR, Almasan A. New agents for the treatment of lymphoid leukemia and lymphoma: focus on recent FDA approvals. Discoveries 2014, Jan-Mar; 2(1): e14.
DOI: 10.15190/d.2014.6.

Submitted: March 22, 2014; Accepted: March 26, 2014; Published: March 31, 2014

 

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New agents for the treatment of lymphoid leukemia and lymphoma: focus on recent FDA approvals


(1), (2), and (3)


Affiliation:
(1) Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA; (2) Department of Hematologic Oncology and Blood Disorders, Cleveland Clinic, OH, USA; (3) Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA

*Correspondence should be addressed to: A. Almasan, Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA. Tel: +1 216 444 9970; Fax: +1 216 445 6269; E-mail: almasaa@ccf.org


Abstract


Leukemia and lymphoma are systemic malignancies that represent half of all childhood cancers, though 90% occur in adults. Various treatment options are available, but therapy is mainly systemic chemotherapy plus appropriate monoclonal antibodies. In certain situations radiotherapy and bone marrow transplantation play a role. Some types/subtypes of these diseases are potentially curable, yet many leukemias and lymphomas do not properly respond to current therapies.
Although the FDA (US Food and Drugs Administration) approvals of new drugs have shown a small increasing trend between 2007-2012, overall, the trend of new approvals remains relatively steady between 2006-2013, with a peak of 39 new drugs approved in 2012 and a drop in the new FDA drug approvals in 2013, to 27. Drugs approved for cancer treatment have shown a similar trend. Between 2006-2013, at least one drug was approved every year for the treatment of particular types of lymphoma or leukemia, except in 2010, with a peak of 5 new approvals in 2012. Between January 2013-March 2014, several important new approvals were made: ibrutinib for the treatment of CLL and mantle cell lymphoma (MCL), obinutuzumab for the treatment of CLL (in combination with chlorambucil), and lenalidomide for the treatment of mantle cell lymphoma. The results, importance, adverse effects and mechanisms of action of these agents are discussed in this review. These results held promise and their discovery and approval for the treatment of CLL and MCL is a major step forward. However, the emergence of resistance and the lack of cures need to be addressed by rational development of combination therapy, as well as development of novel drugs with enhanced potency or different mechanism of action, to achieve better overall and complete response rates with decreased toxicity.

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References

1. Averill LW, Acikgoz G, Miller RE, Kandula VV, Epelman M. Update on pediatric leukemia and lymphoma imaging. Semin Ultrasound CT MR. 2013; 34(6): 578-99. PMID: 24332209; DOI: 10.1053/j.sult.2013.05.004.
2. National Cancer Institute, 2011. "SEER Stat Fact Sheets: Leukemia" http://seer.cancer.gov/statfacts/html/ leuks.html#incidence-mortality (accessed in March 2014)
3. Mosby’s Medical, Nursing &Allied Health Dictionary (Fourth ed.). Mosby-YearBook. 1994. p. 903.
4. Appelbaum FR. The acute leukemias. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine. 24th ed. Philadelphia, PA: Elsevier Saunders; 2011: chap 189.
5. Steele M, Narendran A. Mechanisms of defective erythropoiesis and anemia in pediatric acute lymphoblastic leukemia (ALL). Ann Hematol. 2012 Oct;91(10):1513-8. PMID: 22543829; DOI: 10.1007/s00277-012-1475-5;
6. Allsup DJ, Cawley JC. Diagnosis, biology and treatment of hairy-cell leukaemia. Clin Exp Med. 2004 Dec;4(3):132-8. PMID: 15599661; DOI: 10.1007/s10238-004-0046-z;
7. Martínez-Cuadrón D, Montesinos P, Pérez-Sirvent M, Avaria A, Cordón L, Rodríguez-Veiga R et al. Central nervous system involvement at first relapse in patients with acute myeloid leukemia. Haematologica. 2011;96(9):1375-9. PMID: 21565904; DOI: 10.3324/haematol.2011.042960;
8. Parham, Peter (2005). The immune system. New York: Garland Science. p. 414. ISBN 0-8153-4093-1.
9. Swerdlow, Steven H.; International Agency for Research on Cancer; World Health Organization (2008). WHO classification of tumours of haematopoietic and lymphoid tissues. World Health Organization classification of tumours 2 (4th ed.). International Agency for Research on Cancer. ISBN 9789283224310;
10. Jaffe, Elaine Sarkin (2001). Pathology & Genetics: Tumours of Haematopoietic and Lymphoid Tissues. WHO classification of tumours, pathology and genetics series 3. IARC. ISBN 978-92-832-2411-2;
11. Doria-Rose VP, Harlan LC, Stevens J, Little RF. Treatment of de novo acute myeloid leukemia in the United States: a report from the Patterns of Care program. Leuk Lymphoma. 2014 Mar 7. PMID: 24467221; DOI: 10.3109/10428194.2014.885517;
12. Bucur O, Stancu AL, Goganau I, Petrescu SM, Pennarun B, Bertomeu T, Dewar R, Khosravi-Far R. Combination of bortezomib and mitotic inhibitors down-modulate Bcr-Abl and efficiently eliminates tyrosine-kinase inhibitor sensitive and resistant Bcr-Abl-positive leukemic cells. PLoS One. 2013 Oct 14;8(10):e77390. PMID: 24155950; DOI: 10.1371/journal.pone.0077390;
13. Steinway SN, Leblanc F, Loughran TP Jr. The pathogenesis and treatment of large granular lymphocyte leukemia. Blood Rev. 2014 Mar 7. PMID: 24679833; DOI: 10.1016/j.blre.2014.02.001;
14. Jain P, Pemmaraju N, Ravandi F. Update on the Biology and Treatment Options for Hairy Cell Leukemia. Curr Treat Options Oncol. 2014 Mar 21. PMID: 24652320; DOI: 10.1007/s11864-014-0285-5;
15. Sweet K, Lancet JE. Novel Therapeutics in Acute Myeloid Leukemia. Curr Hematol Malig Rep. 2014 Mar 16. PMID: 24633743; DOI: 10.1007/s11899-014-0199-0;
16. Mazumder S, Choudhary GS, Al-Harbi S, Almasan A. Mcl-1 Phosphorylation defines ABT-737 resistance that can be overcome by increased NOXA expression in leukemic B cells. Cancer Res. 2012;72(12):3069-79. PMID: 22525702; DOI: 10.1158/0008-5472.CAN-11-4106;
17. Dickinson M, Prince HM. Emerging drugs for T-cell lymphoma. Expert Opin Emerg Drugs. 2014 Mar 18. PMID: 24641592; DOI: 10.1517/14728214.2014.896337;
18. Al-Harbi S, Hill BT, Mazumder S, Singh K, Devecchio J, Choudhary G, Rybicki LA, Kalaycio M, Maciejewski JP, Houghton JA, Almasan A. An antiapoptotic BCL-2 family expression index predicts the response of chronic lymphocytic leukemia to ABT-737. Blood. 2011;118(13):3579-90. PMID: 21772052; DOI: 10.1182/blood-2011-03-340364;
19.http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/DrugInnovation/UCM381803.pdf (accessed in March 2014)
20. http://www.centerwatch.com/drug-information/fda-approved-drugs/ (accessed in March 2014)
21.www.onclive.com/web-exclusives/FDA-Approves-Breakthrough-Ibrutinib-for-MCL (accessed in March 2014).
22. Guha M. Imbruvica – next big drug in B-cell cancer – approved by FDA. Nature Biotechnology 2014; 32(2):113-5. PMID: 24509736; DOI: 10.1038/nbt0214-113
23. http://www.fda.gov/newsevents/newsroom/press announcements/ucm385764.htm (accessed in March 2014)
24. http://www.fiercepharma.com/story/jj-pharmacyclics-slap-130000-price-imbruvica-rare-lymphoma/2013-11-14 (accessed in March 2014)
25. Goede V, Fischer K, Busch R, Engelke A, Eichhorst B, Wendtner CM et al. Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. N Engl J Med. 2014 Mar 20; 370(12):1101-10. PMID: 24401022; DOI: 10.1056/NEJMoa1313984.
26. Cameron F, McCormack PL. Obinutuzumab: first global approval. Drugs. 2014, Jan;74(1):147-54. PMID: 24338113; DOI: 10.1007/s40265-013-0167-3;
27. http://www.gene.com/media/press-releases/14559/ 2013-11-01/fda-approves-gazyva-obinutuzumab-for-peo (accessed in March 2014)
28. Golay J, Da Roit F, Bologna L, Ferrara C, Leusen JH, Rambaldi A, Klein C, Introna M. Glycoengineered CD20 antibody obinutuzumab activates neutrophils and mediates phagocytosis through CD16B more efficiently than rituximab. Blood. 2013 Nov 14;122(20):3482-91. PMID: 24106207; DOI: 10.1182/blood-2013-05-504043;
29. The mechanism of anti-CD20-mediated B cell depletion revealed by intravital imaging. J Clin Invest. 2013; 123(12):5098-103. PMID: 24177426; DOI: 10.1172/JCI70972.
30. http://www.medscape.com/viewarticle/822221 (accessed in March 2014)
31. http://www.cancer.gov/cancertopics/druginfo/fda-lenalidomide (accessed in March 2014)
32. Vignon M, Venon MD, Hermine O, Delarue R. Management of mantle cell lymphoma in the elderly: current and potential strategies. Drugs Aging. 2013 Dec;30(12):979-86. PMID: 24178346; DOI: 10.1007/s40266-013-0129-1;
33. Goy A, Sinha R, Williams ME, Kalayoglu Besisik S, Drach J, Ramchandren R et al. Single-agent lenalidomide in patients with mantle-cell lymphoma who relapsed or progressed after or were refractory to bortezomib: phase II MCL-001 (EMERGE) study. J Clin Oncol. 2013 Oct 10; 31(29):3688-95. PMID: 24002500; DOI: 10.1200/JCO.2013.49.2835.
34. Kotla V, Goel S, Nischal S, Heuck C, Vivek K, Das B, Verma A. Mechanism of action of lenalidomide in hematological malignancies. J Hematol Oncol. 2009; 2:36. PMID: 19674465; DOI: 10.1186/1756-8722-2-36;
35. Shortt J, Hsu AK, Johnstone RW. Thalidomide-analogue biology: immunological, molecular and epigenetic targets in cancer therapy. Oncogene. 2013;32(36):4191-202. PMID: 23318436; DOI: 10.1038/onc.2012.599;
36. Moros A, Bustany S, Cahu J, Saborit-Villarroya I, Martínez A, Colomer D, Sola B, Roué G. Antitumoral activity of lenalidomide in in vitro and in vivo models of mantle cell lymphoma involves the destabilization of cyclin D1/p27KIP1 complexes. Clin Cancer Res. 2014 Jan 15;20(2):393-403. PMID: 24178620; DOI: 10.1158/1078-0432.CCR-13-1569;
37. Zhang LH, Kosek J, Wang M, Heise C, Schafer PH, Chopra R. Lenalidomide efficacy in activated B-cell-like subtype diffuse large B-cell lymphoma is dependent upon IRF4 and cereblon expression. Br J Haematol. 2013; 160(4):487-502. PMID: 23252516; DOI: 10.1111/bjh.12172.
38. Phillips CV, Goodman KJ, Poole C; the editors of Epidemiologic Perspectives & Innovations. Lead editorial: The need for greater perspective and innovation in epidemiology. Epidemiol Perspect Innov. 2004;1(1):1. PMID: 15507155; DOI: 10.1186/1742-5573-1-1
39. Bucur O, Almasan A, Nikolajczyk BS, Nicolson GL, Lawler L, Velculescu VE, Draghici S, Leabu M, Avram D, Bucur I, Calautti E, Calin GA, Chauhan SC, Ciubotaru M, Constantinescu SN, Datta D, Duda DG, Friedman MT, Galardy PJ, Harris BT, Huarte M, Khalil AM, Marchetti D, Movileanu L, Nat R, Nucera C, Popa-Wagner A, Stancu AL, Zhu S, Liehn EA . Discoveries: an innovative platform for publishing cutting-edge research discoveries in medicine, biology and chemistry. Discoveries 2013, Oct-Dec; 1(1): e1. DOI: 10.15190/d.2013.1;
40. Anatol R, Bauer S, Epstein S, Filice R, Lauritsen K, Lee MH ET AL. Continuing to strengthen FDA's science approach to emerging technologies. Nanomedicine. 2013 Jul;9(5):594-9. PMID: 23692697; DOI: 10.1016/ j.nano.2013.04.005;
41. Nicolson GL. Update of the 1972 Singer-Nicolson Fluid-Mosaic Model of Membrane Structure. Discoveries 2013, Oct-Dec; 1(1): e3. DOI: 10.15190/d.2013.3;
42. Fiocchi A. Setting the stage of innovations in allergy globally. World Allergy Organ J. 2014 Mar 21;7(1):5. PMID: 24655683; DOI: 10.1186/1939-4551-7-5
43. Discoveries Interview : Prof. Garth L. Nicolson on cellular membrane structure. Discoveries 2013, Oct-Dec; 1(1): e2; DOI: 10.15190/d.2013.2
44. Paugh SW, Stocco G, Evans WE. Pharmacogenomics in pediatric leukemia. Curr Opin Pediatr. 2010; 22(6):703-10. PMID: 20861736; DOI: 10.1097/MOP.0b013e32833fde85;
45. http://www.cancer.org/research/cancerfactsstatistics/ cancerfactsfigures2013/index (accessed in March 2014)
46. Shimada K, Tomita A, Saito S, Kiyoi H. Efficacy of ofatumumab against rituximab-resistant B-CLL/SLL cells with low CD20 protein expression. Br J Haematol. 2014 Mar 27. PMID: 24673649; DOI: 10.1111/bjh.12857;
47. Furtado M, Dyer MJ, Johnson R, Berrow M, Rule S. Ofatumumab monotherapy in relapsed/refractory mantle cell lymphoma - a phase II trial. Br J Haematol. 2014; 165(4):575-8. PMID: 24666179; DOI: 10.1111/bjh.12769;
48. Fruman DA, Cantley LC. Idelalisib--a PI3Kd inhibitor for B-cell cancers. N Engl J Med. 2014; 370(11):1061-2. PMID: 24620870; DOI: 10.1056/NEJMe1400055.
49. Burger JA, Okkenhaug K. Haematological cancer: Idelalisib-targeting PI3Kd in patients with B-cell malignancies. Nat Rev Clin Oncol. 2014 Apr;11(4):184-6. PMID: 24642682; DOI: 10.1038/nrclinonc.2014.42.
50. BCL-2 inhibitor yields high response in CLL and SLL. Cancer Discov. 2014; 4(2):OF5. PMID: 24501317; DOI: 10.1158/2159-8290.CD-NB2013-178;
51. Souers AJ, Leverson JD, Boghaert ER, Ackler SL, Catron ND, Chen J et al. ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat Med. 2013; 19(2): 202-8. PMID: 23291630; DOI: 10.1038/nm.3048;

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