Clinical Trial

. 2022 May 10;40(14):1574-1582.

doi: 10.1200/JCO.21.01766. Epub 2022 Feb 14.

SWOG 1318: A Phase II Trial of Blinatumomab Followed by POMP Maintenance in Older Patients With Newly Diagnosed Philadelphia Chromosome-Negative B-Cell Acute Lymphoblastic Leukemia

Anjali S Advani¹, Anna Moseley^{2

3}, Kristen M O'Dwyer⁴, Brent L Wood^{5

6}, Min Fang⁷, Matthew J Wieduwilt^{8

9}, Ibrahim Aldoss¹⁰, Jae H Park¹¹, Rebecca B Klisovic¹², Maria R Baer¹³, Wendy Stock¹⁴, Rupali R Bhave¹⁵, Megan Othus^{2

3}, Richard C Harvey¹⁶, Cheryl L Willman¹⁶, Mark R Litzow¹⁷, Richard M Stone¹⁸, Elad Sharon¹⁹, Harry P Erba²⁰

Affiliations

¹ Department of Hematologic Oncology and Blood Disorders, Cleveland Clinic, Taussig Cancer Institute, Cleveland, OH.
² SWOG Statistics and Data Management Center, Seattle, WA.
³ Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA.
⁴ Department of Medicine, Hematology/Oncology, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, MN.
⁵ Department of Laboratory Medicine, University of Washington, Seattle, WA.
⁶ Current address: Department of Hematopathology, Children's Hospital of Los Angeles, CA.
⁷ Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA.
⁸ Division of Hematology/Oncology, University of California San Diego Moores Cancer Center, La Jolla, CA.
⁹ Current address: Department of Medicine, University of Oklahoma, Oklahoma City, OK.
¹⁰ Department of Hematology & Hematopoietic Cell Transplantation, Gehr Family Center for Leukemia Research, City of Hope, Duarte, CA.
¹¹ Leukemia Service, Memorial Sloan-Kettering Cancer Center, New York, NY.
¹² Department of Hematology and Medical Oncology, Emory University School of Medicine, Winship Cancer Institute, Atlanta, GA.
¹³ Department of Medicine, Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, MD.
¹⁴ Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, IL.
¹⁵ Division of Medical Oncology and Hematology, Wake Forest School of Medicine, Winston Salem, NC.
¹⁶ Department of Pathology, University of New Mexico, Albuquerque, NM.
¹⁷ Division of Hematology, Mayo Clinic, Rochester, MN.
¹⁸ Department of Medicine, Harvard Medical School, Dana-Farber Cancer Institute, Boston, MA.
¹⁹ Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD.
²⁰ Division of Hematologic Malignancies and Cellular Therapy, Duke University Cancer Institute, Durham, NC.

PMID: 35157496
PMCID: PMC9084435
DOI: 10.1200/JCO.21.01766

Clinical Trial

SWOG 1318: A Phase II Trial of Blinatumomab Followed by POMP Maintenance in Older Patients With Newly Diagnosed Philadelphia Chromosome-Negative B-Cell Acute Lymphoblastic Leukemia

Anjali S Advani et al. J Clin Oncol. 2022.

. 2022 May 10;40(14):1574-1582.

doi: 10.1200/JCO.21.01766. Epub 2022 Feb 14.

Authors

Affiliations

¹ Department of Hematologic Oncology and Blood Disorders, Cleveland Clinic, Taussig Cancer Institute, Cleveland, OH.
² SWOG Statistics and Data Management Center, Seattle, WA.
³ Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA.
⁴ Department of Medicine, Hematology/Oncology, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, MN.
⁵ Department of Laboratory Medicine, University of Washington, Seattle, WA.
⁶ Current address: Department of Hematopathology, Children's Hospital of Los Angeles, CA.
⁷ Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA.
⁸ Division of Hematology/Oncology, University of California San Diego Moores Cancer Center, La Jolla, CA.
⁹ Current address: Department of Medicine, University of Oklahoma, Oklahoma City, OK.
¹⁰ Department of Hematology & Hematopoietic Cell Transplantation, Gehr Family Center for Leukemia Research, City of Hope, Duarte, CA.
¹¹ Leukemia Service, Memorial Sloan-Kettering Cancer Center, New York, NY.
¹² Department of Hematology and Medical Oncology, Emory University School of Medicine, Winship Cancer Institute, Atlanta, GA.
¹³ Department of Medicine, Greenebaum Comprehensive Cancer Center, University of Maryland, Baltimore, MD.
¹⁴ Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, IL.
¹⁵ Division of Medical Oncology and Hematology, Wake Forest School of Medicine, Winston Salem, NC.
¹⁶ Department of Pathology, University of New Mexico, Albuquerque, NM.
¹⁷ Division of Hematology, Mayo Clinic, Rochester, MN.
¹⁸ Department of Medicine, Harvard Medical School, Dana-Farber Cancer Institute, Boston, MA.
¹⁹ Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD.
²⁰ Division of Hematologic Malignancies and Cellular Therapy, Duke University Cancer Institute, Durham, NC.

PMID: 35157496
PMCID: PMC9084435
DOI: 10.1200/JCO.21.01766

Abstract

Purpose: Chemotherapy outcomes in older patients with Philadelphia (Ph) chromosome-negative B-acute lymphoblastic leukemia (ALL) are very poor. Here, we evaluated blinatumomab as induction and consolidation therapy followed by prednisone, vincristine, 6-mercaptopurine, and methotrexate (POMP) maintenance chemotherapy in this patient population.

Patients and methods: Patients were treated at National Clinical Trial Network sites. Eligibility criteria included age ≥ 65 years and newly diagnosed Ph chromosome-negative B-ALL. Patients received blinatumomab as induction for one-two cycles until attainment of response (complete remission (CR) and CR with incomplete count recovery). Patients then received three cycles of consolidation with blinatumomab followed by 18 months of POMP maintenance chemotherapy. Eight doses of intrathecal methotrexate were administered as central nervous system prophylaxis.

Results: Twenty-nine eligible patients were enrolled. The median age was 75 years, and the median bone marrow blast count at diagnosis was 87%. Cytogenetic risk was poor in 10 patients (34%), and five of 14 patients (36%) tested had the Ph-like ALL gene signature. Nineteen patients (66%; 95% CI, 46 to 82) achieved CR. Kaplan-Meier 3-year disease-free survival and overall survival estimates were 37% (95% CI, 17 to 57) and 37% (95% CI, 20 to 55), respectively.

Conclusion: Blinatumomab was well tolerated and effective in the treatment of older patients with newly diagnosed Ph chromosome-negative B-ALL, including patients with poor-risk cytogenetics. The 3-year disease-free survival and overall survival results are encouraging and suggest that this approach should be further explored.

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Conflict of interest statement

Anjali S. AdvaniHonoraria: PfizerConsulting or Advisory Role: Novartis, GlycoMimetics, Kite, a Gilead company, Seattle Genetics, Amgen, Beam Therapeutics, Jazz Pharmaceuticals, Nkarta, Taiho OncologyResearch Funding: Pfizer (Inst), Millennium (Inst), KaloBios (Inst), Seattle Genetics (Inst), AbbVie (Inst), GlycoMimetics (Inst), MacroGenics (Inst), Pfizer (Inst), Amgen (Inst), Trillium Therapeutics (Inst), Seattle Genetics (Inst), Immunogen (Inst), SERVIER (Inst), Kite/Gilead (Inst), Incyte (Inst), OBI Pharma (Inst) Anna MoseleyConsulting or Advisory Role: BioSight Kristen M. O'DwyerConsulting or Advisory Role: Beam Therapeutics Brent L. WoodHonoraria: Amgen, Seattle Genetics, AbbVie, Janssen, Amgen, Astellas Pharma, Roche Diagnostics, Beckman CoulterConsulting or Advisory Role: SysmexResearch Funding: Amgen (Inst), Seattle Genetics (Inst), Pfizer (Inst), Juno Therapeutics (Inst), BioLineRx (Inst), BioSight (Inst), Stemline Therapeutics (Inst), Janssen Oncology (Inst), Novartis, Kite, a Gilead company (Inst), MacroGenics (Inst)Travel, Accommodations, Expenses: Amgen, Amgen Min FangConsulting or Advisory Role: UnityDxResearch Funding: Nucleix (Inst) Matthew J. WieduwiltStock and Other Ownership Interests: Reata PharmaceuticalsHonoraria: Gilead Sciences, ServierConsulting or Advisory Role: Gilead Sciences, ServierResearch Funding: NCI (Inst)Travel, Accommodations, Expenses: Gilead Sciences Ibrahim AldossHonoraria: Amgen, AbbVie, Kite, a Gilead company, Agios, Jazz PharmaceuticalsConsulting or Advisory Role: AmgenSpeakers' Bureau: PfizerResearch Funding: AbbVie, MacroGenics Jae H. ParkConsulting or Advisory Role: Amgen, Novartis, Pfizer, Kite, a Gilead company, Autolus, Takeda, Servier, Incyte, Intellia Therapeutics, Innate Pharma, Artiva, Bristol Myers Squibb/Celgene/Juno, Kura Oncology, Kura Oncology, Kura Oncology, Minerva Biotechnologies, Precision Biosciences, AffyImmune Therapeutics, BeiGeneResearch Funding: Juno Therapeutics (Inst), Genentech/Roche (Inst) Rebecca B. KlisovicConsulting or Advisory Role: Novartis, Visante, AbbVie, Bristol Myers Squibb, PfizerResearch Funding: Pfizer, ARIAD, Bristol Myers Squibb, Avillion, NovartisTravel, Accommodations, Expenses: Novartis Maria R. BaerResearch Funding: AbbVie (Inst), FORMA Therapeutics (Inst), Kite, a Gilead company (Inst), Takeda (Inst), Kura Oncology (Inst), Ascentage Pharma (Inst) Wendy StockHonoraria: Amgen, PfizerConsulting or Advisory Role: Agios, Amgen, Astra Zeneca, Beam, Glaxo Smith Kline, Jazz, Kite, Kronos, Kura, Morphosys, Newave, Pfizer, Pluristem, Servier, SyndaxPatents, Royalties, Other Intellectual Property: Royalties for a chapter in UpToDate Megan OthusConsulting or Advisory Role: GlycoMimetics, Cascadia Labs, Merck, Daiichi Sankyo, BioSightOther Relationship: Celgene, GlycoMimetics Cheryl L. WillmanPatents, Royalties, Other Intellectual Property: I have three patents for genomic diagnostics. They are all held by the University of New Mexico and have been licensed by TriCore Reference Laboratories. One generates minimal annual royalties (< $5,000 US dollars) Mark R. LitzowConsulting or Advisory Role: Omeros, Jazz PharmaceuticalsResearch Funding: Amgen, Astellas Pharma, Actinium Pharmaceuticals, Pluristem Therapeutics, AbbVie/Genentech, Tolero Pharmaceuticals, AbbVieOther Relationship: BioSight Richard M. StoneHonoraria: Prime Oncology, Medscape, Research to Practice, DAVA PharmaceuticalsConsulting or Advisory Role: Amgen, AbbVie, Agios, Celgene, Novartis, Actinium Pharmaceuticals, Arog, Astellas Pharma, MacroGenics, Takeda, BioLineRx, Daiichi-Sankyo, Trovagene, GEMoaB, Syntrix Biosystems, ElevateBio, Syndax, Syros Pharmaceuticals, BerGenBio, Janssen, Innate Pharma, Foghorn Therapeutics, Aprea Therapeutics, GlaxoSmithKline, CTI BioPharma Corp, Bristol Myers Squibb, Boston Pharmaceuticals, Onconova Therapeutics, Jazz PharmaceuticalsResearch Funding: Novartis (Inst), Agios (Inst), AbbVie/Genentech (Inst) Harry P. ErbaConsulting or Advisory Role: Agios, Astellas Pharma, Amgen, Celgene, Daiichi Sankyo, GlycoMimetics, Immunogen, Incyte, Jazz Pharmaceuticals, MacroGenics, Novartis, AbbVie/Genentech, Janssen Oncology, Pfizer, Trillium Therapeutics, Takeda, Kura OncologySpeakers' Bureau: Agios, Celgene, Incyte, Jazz Pharmaceuticals, Novartis, AbbVie/GenentechResearch Funding: AbbVie, Agios (Inst), Amgen (Inst), Daiichi Sankyo (Inst), FORMA Therapeutics (Inst), Gilead/Forty Seven (Inst), Immunogen (Inst), Jazz Pharmaceuticals (Inst), MacroGenics (Inst), Novartis (Inst), PTC Therapeutics (Inst), AbbVie (Inst), GlycoMimetics (Inst), ALX Oncology (Inst)Other Relationship: GlycoMimetics, CelgeneUncompensated Relationships: Daiichi SankyoNo other potential conflicts of interest were reported.

Figures

**FIG 1.**
Treatment schema. Eight doses of IT methotrexate were given as CNS prophylaxis. CR, complete remission; CRi, CR with incomplete count recovery; IT, intrathecal; POMP, prednisone, vincristine, 6-mercaptopurine, and methotrexate.

**FIG 2.**
Flow diagram. AE, adverse event; CR, complete remission.

**FIG 3.**
(A) Kaplan-Meier DFS (blue) with two-sided 95% CI (gray), and (B) Kaplan-Meier OS (blue) with one-sided 90% CI (gray). CR, complete remission; DFS, disease-free survival; OS, overall survival.

**FIG A1.**
(A) DFS by Ph-like status. (B) OS by Ph-like status. DFS, disease-free survival; OS, overall survival; Ph, Philadelphia.

**FIG A2.**
(A) DFS by cytogenetic risk. (B) OS by cytogenetic risk. DFS, disease-free survival; OS, overall survival.

See this image and copyright information in PMC

References

1. National Cancer Institute : SEER stat fact sheet: Acute lymphocytic leukemia. Bethesda, MD, 2012. http://seer.cancer.gov/statfacts/html/alyl.html
1. O’Brien S, Thomas DA, Ravandi F, et al. : Results of the hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone regimen in elderly patients with acute lymphocytic leukemia. Cancer 113:297-2101, 2008 - PMC - PubMed
1. Sive J, Buck G, Fielding A, et al. : Outcomes in older adults with acute lymphoblastic leukemia (ALL): Results from the international MRC UKALL XII/ECOG 2993 trial. Br J Haematol 157:463-471, 2012 - PMC - PubMed
1. Stock W: personal communication. Data from 5 CALGB trials 1988-2001
1. Larson RA: The US trials in adult acute lymphoblastic leukemia. Ann Hematol 83:S127-S128, 2004. (suppl I) - PubMed

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SWOG 1318: A Phase II Trial of Blinatumomab Followed by POMP Maintenance in Older Patients With Newly Diagnosed Philadelphia Chromosome-Negative B-Cell Acute Lymphoblastic Leukemia

Affiliations

SWOG 1318: A Phase II Trial of Blinatumomab Followed by POMP Maintenance in Older Patients With Newly Diagnosed Philadelphia Chromosome-Negative B-Cell Acute Lymphoblastic Leukemia

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Conflict of interest statement

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