Apr 21, 2023
By Jasenka Piljac Zegarac, PhD
Hagop Kantarjian, MD, of The University of Texas MD Anderson Cancer Center (MD Anderson), will receive the 2023 David A. Karnofsky Memorial Award for his contributions to the development of novel therapies for several types of leukemia, and his dedication to improving the lives of patients with cancer.
The David Karnofsky Memorial Award “is the Society’s highest scientific honor, and I am humbled and deeply honored to be its recipient this year,” said Dr. Kantarjian. He will present a lecture during the ASCO Annual Meeting on June 3.
Dr. Kantarjian is known for his practice-changing translational research accomplishments in leukemia. His work has transformed the standards of care for several subtypes of leukemia and led to significant improvements in the survival of patients with chronic myeloid leukemia (CML), acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), and myelodysplastic syndrome (MDS).
A Fateful Visit to MD Anderson
Dr. Kantarjian received his medical degree from the American University of Beirut in Lebanon in 1979 and completed his residency in internal medicine at the same institution in 1981. However, it was his time at MD Anderson as a young medical student, and later as a fellow, that helped shaped his lifelong career interests in leukemia.
“In 1978, I took a 4-month elective and chose to come to MD Anderson because of its reputation as one of the two most innovative cancer research centers in the world,” he said. “I was drowned in a new environment where amazing things were happening. The mentors who shaped my career and guided my thinking and approach to leukemia research were Drs. Emil J. Freireich, Kenneth McCredie, and Michael Keating; all three helped me throughout my research career.
“When I came to MD Anderson, I fell in love with the institution and the researchers’ innovative approaches,” he added. “I thought, if cancer is going to be cured in the next decades, surely this place may be one of the world’s leaders in this. I decided to apply to MD Anderson for cancer training. I came back in 1981, completed my training in oncology in 1983, joined the leukemia program, and have been a leukemia researcher until today and, hopefully, will continue to do so for the rest of my professional career.”
Transforming the Outcomes of Patients With Leukemia
In 1981, the two chronic leukemias—CML and CLL—were incurable and the cure rates for two acute leukemias—AML and ALL—were approximately 20% to 30%.
“Today, CML is functionally curable; people live a normal life with BCR::ABL1 tyrosine kinase inhibitor (TKI) therapies,” he said.
Dr. Kantarjian noted that following the discovery of imatinib activity in CML by Dr. Brian Druker, the MD Anderson leukemia team either participated in, or led the development of, several TKIs for CML including imatinib, dasatinib, nilotinib, bosutinib, ponatinib, and, most recently, olverembatinib.1-6
In CLL, Drs. Nitin Jain, William (Bill) Wierda, Jan Burger, and Michael Keating from MD Anderson and other groups, have developed a combination approach consisting of ibrutinib, a Bruton TKI, and venetoclax, which dramatically improved the survival of patients with CLL.7,8 Dr. Kantarjian is hopeful that such combinations of Bruton TKIs plus venetoclax may change the outcome of CLL from incurable cancer to highly curable.
His team is also credited for pioneering the hyper-CVAD regimen in 1992 and establishing it as a standard of care in adult ALL.9 Subsequently, his group developed hyper-CVAD derivative regimens, including combined modality therapies with the BCR-ABL1 TKIs in Philadelphia-positive ALL.10 In 2017, he pioneered a nonchemotherapy-based regimen consisting of ponatinib and blinatumomab for Philadelphia-positive ALL. The updated findings for this combination indicate a 4-year survival rate of more than 90%.11
“In the setting of adult pre-B ALL, following our pilot investigational new drug studies with inotuzumab ozogamicin, and the U.S. Food and Drug Administration (FDA) pivotal trials of inotuzumab ozogamicin and blinatumomab, we developed in the past decade new regimens combining less chemotherapy with the new CD19 and CD22 antibodies,” he said. “These have increased the 4-year survival rate in adult ALL to close to more than 80%”12-14 His work in ALL extends to the research and development of several antibodies including inotuzumab ozogamicin and blinatumomab, both approved by the U.S. Food and Drug Administration (FDA) as salvage treatments for ALL.12,13
In AML and MDS, he spearheaded the development of decitabine and epigenetic hypomethylation therapy in older or unfit patients with AML, along with Dr. Jean-Pierre Issa. This led to the FDA approval of decitabine in MDS in 2006, and to its the European approval for older AML in 2012.15,16 Dr. Kantarjian’s group was the first to test hypomethylating agents in combination with venetoclax, which led to the pivotal trial and FDA approval this combination in older or unfit patients with AML in 2018.17
“In older or unfit patients with AML, lower intensity chemotherapy (triple-nucleosides) with venetoclax has improved the 3-year survival from less than 20% to 40% or more. In younger patients with AML, incorporating venetoclax and other targeted therapies like FLT3 and IDH inhibitors into the intensive chemotherapy regimens has improved the survival from less than 30% to 40% to more than 50% to 60%,” he said.18,19
The MD Anderson leukemia group also developed other FDA-approved targeted therapies: ivosidenib (an IDH1 inhibitor) in AML, ruxolitinib (a JAK2 inhibitor) in myelofibrosis, tagraxofusp (a CD123 antibody conjugate) in blastic plasmacytoid dendritic cell neoplasm, and clofarabine and liposomal vincristine in ALL.20-23
A Continued Focus on Acute Leukemias
His current research revolves around improving the therapies and outcomes of patients with ALL and AML.
“In ALL, we are interested in furthering the concept of shorter and less chemotherapy, with the introduction of newer antibodies,” he said. “We are trying to develop novel, in-house, tri-specific T-cell engagers that would be a precision treatment for ALL and may potentially lead to the cure of ALL without or with the use of minimal chemotherapy.”
In AML, his team is focused on optimizing the combinations of novel targeted therapies with chemotherapy.
According to Dr. Kantarjian, the remaining challenges in AML and ALL include developing novel effective targeted therapies that are less toxic compared with the traditional intensive chemotherapy-based approaches, and accelerating the time it takes for a new drug approval to five years or less.
Putting Patients First Through Advocacy
Another important barrier in battling leukemia are high prices of cancer drugs. Dr. Kantarjian became interested in this topic after witnessing the skyrocketing prices of TKIs and the devastating effects that health care inaccessibility can have on the lives of patients with cancer.
“When we developed the first TKI imatinib in 2000, the cost of the drug was $32,000 a year. In 2012, it increased to $120,000 a year,” he said. “This is the trend across all the cancer drugs and across drugs outside the field of cancer research. Today, the average price of a newly approved cancer drug exceeds $200,000 a year.”
His concern for patients has led him on a path of advocacy for lowered drug prices and affordable, universal health care. He has been outspoken about these topics and remains interested in keeping these discussions alive. 24-26
“I have a keen interest in the issues of health care and barriers to optimal and affordable health care in the United States and elsewhere in the world,” he said.
He added that roughly one in four Americans cannot afford treatment with optimal therapeutic regimens for their leukemia.
“[These barriers] need to be addressed so that we can optimize and equalize the health care across the different strata of Americans,” he said. “I think it is very important that patients with leukemia receive the same best care, whether they are poor or wealthy.”
- Kantarjian H, Sawyers C, Hochhaus A, et alInternational STI571 CML Study Group. Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N Engl J Med. 2002;346(9):645-652. https://doi.org/10.1056/NEJMoa011573.PubMed
- Talpaz M, Shah NP, Kantarjian H, et al. Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias. N Engl J Med. 2006;354(24):2531-2541. https://doi.org/10.1056/NEJMoa055229.PubMed
- Kantarjian H, Shah NP, Hochhaus A, et al. Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med. 2010;362(24):2260-2270. https://doi.org/10.1056/NEJMoa1002315.PubMed
- Kantarjian H, Giles F, Wunderle L, et al. Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. N Engl J Med. 2006;354(24):2542-2551. https://doi.org/10.1056/NEJMoa055104.PubMed
- Kantarjian HM, Hughes TP, Larson RA, et al. Long-term outcomes with frontline nilotinib versus imatinib in newly diagnosed chronic myeloid leukemia in chronic phase: ENESTnd 10-year analysis. Leukemia. 2021;35(2):440-453. https://doi.org/10.1038/s41375-020-01111-2.PubMed
- Cortes JE, Kantarjian H, Shah NP, et al. Ponatinib in refractory Philadelphia chromosome-positive leukemias. N Engl J Med. 2012;367(22):2075-2088. https://doi.org/10.1056/NEJMoa1205127.PubMed
- Jain N, Keating M, Thompson P, et al. Ibrutinib and Venetoclax for First-Line Treatment of CLL. N Engl J Med. 2019;380(22):2095-2103. https://doi.org/10.1056/NEJMoa1900574.PubMed
- Jain N, Keating M, Thompson P, et al. Ibrutinib Plus Venetoclax for First-line Treatment of Chronic Lymphocytic Leukemia: A Nonrandomized Phase 2 Trial. JAMA Oncol. 2021;7(8):1213-1219. https://doi.org/10.1001/jamaoncol.2021.1649.PubMed
- Kantarjian HM, O’Brien S, Smith TL, et al. Results of treatment with hyper-CVAD, a dose-intensive regimen, in adult acute lymphocytic leukemia. J Clin Oncol. 2000;18(3):547-561. https://doi.org/10.1200/JCO.2000.18.3.547.PubMed
- Jabbour E, Kantarjian H, Ravandi F, et al. Combination of hyper-CVAD with ponatinib as first-line therapy for patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia: a single-centre, phase 2 study. Lancet Oncol. 2015;16(15):1547-1555. https://doi.org/10.1016/S1470-2045(15)00207-7.PubMed
- Jabbour E, Short NJ, Jain N, et al. Ponatinib and blinatumomab for Philadelphia chromosome-positive acute lymphoblastic leukaemia: a US, single-centre, single-arm, phase 2 trial. Lancet Haematol. 2023;10(1):e24-e34. https://doi.org/10.1016/S2352-3026(22)00319-2.PubMed
- Kantarjian HM, DeAngelo DJ, Stelljes M, et al. Inotuzumab Ozogamicin versus Standard Therapy for Acute Lymphoblastic Leukemia. N Engl J Med. 2016;375(8):740-753. https://doi.org/10.1056/NEJMoa1509277.PubMed
- Kantarjian H, Stein A, Gökbuget N, et al. Blinatumomab versus Chemotherapy for Advanced Acute Lymphoblastic Leukemia. N Engl J Med. 2017;376(9):836-847. https://doi.org/10.1056/NEJMoa1609783.PubMed
- Jabbour E, Short NJ, Jain N, et al. Hyper-CVAD and sequential blinatumomab for newly diagnosed Philadelphia chromosome-negative B-cell acute lymphocytic leukaemia: a single-arm, single-centre, phase 2 trial. Lancet Haematol. 2022;9(12):e878-e885. https://doi.org/10.1016/S2352-3026(22)00285-X.PubMed
- Kantarjian H, Issa JP, Rosenfeld CS, et al. Decitabine improves patient outcomes in myelodysplastic syndromes: results of a phase III randomized study. Cancer. 2006;106(8):1794-1803. https://doi.org/10.1002/cncr.21792.PubMed
- Kantarjian HM, Thomas XG, Dmoszynska A, et al. Multicenter, randomized, open-label, phase III trial of decitabine versus patient choice, with physician advice, of either supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia. J Clin Oncol. 2012;30(21):2670-2677. https://doi.org/10.1200/JCO.2011.38.9429.PubMed
- DiNardo CD, Jonas BA, Pullarkat V, et al. Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia. N Engl J Med. 2020;383(7):617-629. https://doi.org/10.1056/NEJMoa2012971.PubMed
- Kadia TM, Reville PK, Wang X, et al. Phase II Study of Venetoclax Added to Cladribine Plus Low-Dose Cytarabine Alternating With 5-Azacitidine in Older Patients With Newly Diagnosed Acute Myeloid Leukemia. J Clin Oncol. 2022;40(33):3848-3857. https://doi.org/10.1200/JCO.21.02823.PubMed
- Lachowiez CA, Reville PK, Kantarjian H, et al. Venetoclax combined with induction chemotherapy in patients with newly diagnosed acute myeloid leukaemia: a post-hoc, propensity score-matched, cohort study. Lancet Haematol. 2022;9(5):e350-e360. https://doi.org/10.1016/S2352-3026(22)00076-X.PubMed
- DiNardo CD, Stein EM, de Botton S, et al. Durable Remissions with Ivosidenib in IDH1-Mutated Relapsed or Refractory AML. N Engl J Med. 2018;378(25):2386-2398. https://doi.org/10.1056/NEJMoa1716984.PubMed
- Verstovsek S, Kantarjian H, Mesa RA, et al. Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis. N Engl J Med. 2010;363(12):1117-1127. doi:https://doi.org/10.1056/NEJMoa1002028.PubMed
- Verstovsek S, Mesa RA, Gotlib J, et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med. 2012;366(9):799-807. https://doi.org/10.1056/NEJMoa1110557.PubMed
- Pemmaraju N, Lane AA, Sweet KL, et al. Tagraxofusp in Blastic Plasmacytoid Dendritic-Cell Neoplasm. N Engl J Med. 2019;380(17):1628-1637. https://doi.org/10.1056/NEJMoa1815105.PubMed
- Kantarjian H, Paul S, Thakkar J, Jabbour E. The influence of drug prices, new availability of inexpensive generic imatinib, new approvals, and post-marketing research on the treatment of chronic myeloid leukaemia in the USA. Lancet Haematol. 2022;9(11):e854-e861. https://doi.org/10.1016/S2352-3026(22)00246-0.PubMed
- Kantarjian H, Steensma D, Light D. Should oncologists support the Affordable Care Act? Lancet Oncol. 2013;14(13):1258-1259. https://doi.org/10.1016/S1470-2045(13)70544-8.PubMed
- Jones GH, Kantarjian H. Health care in the United States--basic human right or entitlement? Ann Oncol. 2015;26(10):2193-2195. https://doi.org/10.1093/annonc/mdv321.PubMed