Existing users Log In New users Sign up

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

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


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


GO BACK to 2014, January-March issue

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

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

(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


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.

Access full text of the manuscript here:


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;

GO BACK to 2014, January-March issue

Email Email us at info@discoveriesjournals.org if you have any questions.

News & Events Latest news from our journals.

  • 2022| Discoveries Reports

    Access the new website of DISCOVERIES REPORTS at: discoveries-reports.com. 

  • 2022, April| AWARDS!

    2022 Discoveries Award winning articles!

    - Kinal Bhatt et al. 2021 (Larking Health System, FL, USA); Bhatt K, Agolli A, Patel MH, et al. High mortality co-infections of COVID-19 patients: mucormycosis and other fungal infections. Discoveries. 2021;9(1):e126. 
    27 citations in the past 1 year - $1000 prize

    - Hasnain Jan et al. 2020 (Quaid-i-Azam University, Pakistan); Jan H, Faisal S, Khan A, et al. COVID-19: Review of Epidemiology and Potential Treatments Against 2019 Novel Coronavirus. Discoveries. 2020;8(2):e108. 
    23 citations in the past 2 years - $400 prize

    Congratulations! Prizes will be received by the awardees in July, 2022!.

  • 2021, January| AWARDS!

    2022 DISCOVERIES AWARDS! Discoveries will offer $1000 and $400 awards in early 2022, for the most cited (2021 ISI Citations) and visible (Altmetric Score) articles published in 2018-2021.

  • 2020, November| Discoveries on Twitter!

    You can now follow the latest Discoveries news and updates on Twitter! (@DiscoveriesNews) 

  • 2020, August| For Authors!

    Due to a high volume of article submissions, our peer-review process takes more than usual. The pre-screening decision is released in 1-2 days, while the peer-review process lasts between 10 and 20 days.  

  • 2020, April | For Authors!

    WE DO NOT TOLERATE ANY MISCONDUCT! Please be aware that we are testing all received articles with specialized software for PLAGIARISM and WE WILL TAKE MEASURES if your article is already published or in consideration for publication by other journals! This may result in serious professional consequences for the authors. The latest striking case is the following article which is already published and was re-submitted here.  

  • 2020, April | For Authors!

    We are happy to let you know that all articles published in Discoveries are now on PubMedCentral (PMC). New accepted articles will be included in PMC and PubMed within 1-2 weeks after their publication.

  • 2020, January | For Authors!

    Starting in January 2020, Discoveries will also consider articles submitted by Discoveries' Editorial Board members. However, only a small number of such articles (maximum 4 articles/year) will be considered for publication after the peer-review process, and the authors who are also our editors will be clearly disclosed. 

  • 2019, September | Indexed by PMC

    Discoveries is now indexed by PubMedCentral and Pubmed. The agreement with US National Library of Medicine was signed on September 10, 2019. Our next step is ISI Web of Science indexing. NOTE: previously published articles will be included on PubMed in early 2020.

  • 2019, September | PubMed inclusion!

    We are happy to let you know that Discoveries successfuly passed the last step (Technical Review) required for PubMedCentral and PubMed inclusion!

  • 2019, June | PubMed inclusion News!

    We are happy to receive positive comments from PMC/NLM-NIH regarding Discoveries' last step (Technical Review) required for PubMedCentral and PubMed inclusion. We will let you know once whole indexing process is completed. 

  • 2018-2019 | For Authors!

    From now on and for at least 1 year, we will only accept articles from authors that are NOT members of Discoveries' Editorial Board. All articles submitted by our editors will be immediately rejected until further notice. 

  • 2018 | PubMed inclusion News!

    Discoveries successfully passed the Scientific Quality Review by NLM-NIH for PubMedCentral and PubMed indexing. This is the first and the most important step towards PubMedCentral and PubMed indexing! The second (last) step is the Technical Review.

  • April 2016 | Faster Peer-Review

    Starting on April 13th, all articles selected for a peer-review will receive the post peer-review decision within 10 days. The initial pre-screening time will remain the same (48h from the submission of the manuscript). This decision will significantly accelerate the publication, with no effect on the quality of the peer-review process.

  • February 2016 | Manuscript submission

    Discoveries is commited to excellence, quality and high editorial standards. We are receiving an increasing number of manuscripts for which the identity of the authors/corresponding author can't be verified. Please NOTE that ALL these articles were and will be immediately REJECTED. Indicating an institutional email address is the easiest way to overcome this problem! Moreover, we do not accept any pressure on our editorial board to accept a manuscript. This results in a prompt rejection of the article.

    Editorial Policies
  • January 2016 |Discoveries-AIM

    After reaching all proposed milestones until now (including being indexed by Google Scholar in 2014), Discoveries' next Aim is PubMed indexing of all its articles (already published and upcoming). There will be no charge for the submission or publication of articles in Discoveries before PubMed indexing.

  • August 2015 | Discoveries - on PubMed

    We are happy to announce that our first Discoveries articles were included in PMC and PubMed. More articles (submitted by NIH funded articles) are now processed for being included.

    Discoveries articles now on PubMed
  • April 2015 | Special Issue

    DISCOVERIES publish the SPECIAL ISSUE entitled "INFLAMMATION BETWEEN DEFENSE AND DISEASE: Impact on Tissue Repair and Chronic Sickness".

    Special Issue on "Inflammation"
  • 2015 | Ischemia Collection

    DISCOVERIES launched a call for papers for a Collection of Articles with focus on "ISCHEMIA". If you are interested to submit a manuscript, please contact us at info@discoveriesjournals.org

  • October 2014 | Special Issue

    DISCOVERIES launched a call for papers, for the SPECIAL ISSUE entitled "INFLAMMATION BETWEEN DEFENSE AND DISEASE: Impact on Tissue Repair and Chronic Sickness".

  • September 2014 | Special Issue

    DISCOVERIES just publish the SPECIAL ISSUE entitled "CELL SECRETION & MEMBRANE FUSION" in September 2014. Initially scheduled for publication between October 2014-March 2015, this issue was successfully published earlier than scheduled. 

    Special Issue
  • April 2014 | Indexed by Google Scholar

    All our published articles are now indexed by Google Scholar! Current citations for each individual article published in either Discoveries or Discoveries Reports are also shown. First citations to Discoveries articles are included! Search for the article's title or the authors:

    Google Scholar Search

  • July 2013 | Manuscript Submission

    Submit your manuscript FREE, FAST and EASY ! (in less than 1 minute)
    There are NO fees for the manuscript submission or publishing of the accepted manuscripts.

    Read more

  • July 2013 | DISCOVERIES

    We are now ACCEPTING MANUSCRIPTS for publishing in DISCOVERIES. We aim to publish a small number of high impact experimental articles & reviews (around 40/year) to maintain a high impact factor. Domains of interest: all areas related to Medicine, Biology and Chemistry ...

    Read more


    We are now ACCEPTING MANUSCRIPTS for DISCOVERIES REPORTS, publishing inovative and important research findings from all areas related to Medicine, Biology and Chemistry. We are also accepting experimental articles that validate/invalidate highly used reagents in current publications (ex. antibodies) and selected articles presenting negative data with impact and of wide scientific interest ...

    Read more

Member Login
Free Registration Click here to sign up
Copyright © 2013 Applied Systems. All Rights Reserved.