Dual targeting fixed duration frontline monoclonal antibody therapy for chronic lymphocytic leukemia: A phase 2 study

Shuo Ma; Steven T. Rosen; Maria Winqvist; Olga Frankfurt; Jane N. Winter; Leo Gordon; Irene Helenowski; Hui Zhang; Jennifer Kreutzer; Sonja Sönnert-Husa; Anders Österborg; Jeanette Lundin

doi:10.1016/j.leukres.2022.106945

Dual targeting fixed duration frontline monoclonal antibody therapy for chronic lymphocytic leukemia: A phase 2 study

Shuo Ma, Steven T. Rosen, Maria Winqvist, Olga Frankfurt, Jane N. Winter, Leo Gordon, Irene Helenowski, Hui Zhang, Jennifer Kreutzer, Sonja Sönnert-Husa, Anders Österborg, Jeanette Lundin^*

^*Corresponding author for this work

Medicine, Hematology Oncology Division

Research output: Contribution to journal › Article › peer-review

Abstract

This phase 2 study describes long-term clinical and immunological effects of fixed-duration ofatumumab (anti-CD20) and alemtuzumab (anti-CD52) combination immunotherapy in 52 patients with previously untreated CLL. The median age was 65 years (range 45–79), 60% had Rai stage 3–4, 40% were IgHV unmutated and 25% had del(17p)/TP53 mutation. Alemtuzumab was given subcutaneously (30 mg tiw, 18 weeks) and ofatumumab intravenously (300–2000 mg) starting week 3 q2 weeks (8 doses). Overall response rate was 98% with 48% complete remissions including 60% bone marrow MRD-undetectable. After a median follow-up time of 68 months, the median PFS, TTNT, DOR and OS were 31, 62, 30 months and not reached, respectively. The estimated 5-year PFS, TTNT, DOR and OS were 35%, 51%, 35% and 87%, respectively. CD59 (complement-inhibitory molecule) was rapidly downregulated (p < 0.01) during the initial CD52 mAb run-in period. Our study demonstrated that dual targeting of CD20 and CD52 represents an early successful example of time-limited (4–5 months) chemotherapy-free precision therapy for previously untreated CLL.

Original language	English (US)
Article number	106945
Journal	Leukemia Research
Volume	122
DOIs	https://doi.org/10.1016/j.leukres.2022.106945
State	Published - Nov 2022

Funding

S Ma: Research funding from Abbvie, AstraZeneca, BeiGene, Juno, Loxo, Pharmacyclics, and TG Therapeutics; Consultancy/advisory role for Abbvie, AstraZeneca, BeiGene, Genentech, Pharmacyclics, TG Terapeutics, and Verastem; Speakers bureau participation for AstraZeneca, BeiGene, Janssen, and Pharmacyclics. J Winter: Merck Spouse to J Winter: Epizyme, CVS/Caremark and Novartis. L Gordon: BMS and Calithera. J Lundin: Research funding from GSK and Novartis. A Österborg: Research funding from Janssen, AstraZeneca, Beigene, Gilead and Loxo Inc. The other authors had nothing to disclose.

Keywords

Alemtuzumab
CLL
Fixed duration
Frontline treatment
Immunotherapy
Ofatumumab

ASJC Scopus subject areas

Hematology
Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.leukres.2022.106945

Cite this

Ma, S., Rosen, S. T., Winqvist, M., Frankfurt, O., Winter, J. N., Gordon, L., Helenowski, I., Zhang, H., Kreutzer, J., Sönnert-Husa, S., Österborg, A., & Lundin, J. (2022). Dual targeting fixed duration frontline monoclonal antibody therapy for chronic lymphocytic leukemia: A phase 2 study. Leukemia Research, 122, Article 106945. https://doi.org/10.1016/j.leukres.2022.106945

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title = "Dual targeting fixed duration frontline monoclonal antibody therapy for chronic lymphocytic leukemia: A phase 2 study",

abstract = "This phase 2 study describes long-term clinical and immunological effects of fixed-duration ofatumumab (anti-CD20) and alemtuzumab (anti-CD52) combination immunotherapy in 52 patients with previously untreated CLL. The median age was 65 years (range 45–79), 60% had Rai stage 3–4, 40% were IgHV unmutated and 25% had del(17p)/TP53 mutation. Alemtuzumab was given subcutaneously (30 mg tiw, 18 weeks) and ofatumumab intravenously (300–2000 mg) starting week 3 q2 weeks (8 doses). Overall response rate was 98% with 48% complete remissions including 60% bone marrow MRD-undetectable. After a median follow-up time of 68 months, the median PFS, TTNT, DOR and OS were 31, 62, 30 months and not reached, respectively. The estimated 5-year PFS, TTNT, DOR and OS were 35%, 51%, 35% and 87%, respectively. CD59 (complement-inhibitory molecule) was rapidly downregulated (p < 0.01) during the initial CD52 mAb run-in period. Our study demonstrated that dual targeting of CD20 and CD52 represents an early successful example of time-limited (4–5 months) chemotherapy-free precision therapy for previously untreated CLL.",

keywords = "Alemtuzumab, CLL, Fixed duration, Frontline treatment, Immunotherapy, Ofatumumab",

author = "Shuo Ma and Rosen, {Steven T.} and Maria Winqvist and Olga Frankfurt and Winter, {Jane N.} and Leo Gordon and Irene Helenowski and Hui Zhang and Jennifer Kreutzer and Sonja S{\"o}nnert-Husa and Anders {\"O}sterborg and Jeanette Lundin",

note = "Funding Information: S Ma: Research funding from Abbvie, AstraZeneca, BeiGene, Juno, Loxo, Pharmacyclics, and TG Therapeutics; Consultancy/advisory role for Abbvie, AstraZeneca, BeiGene, Genentech, Pharmacyclics, TG Terapeutics, and Verastem; Speakers bureau participation for AstraZeneca, BeiGene, Janssen, and Pharmacyclics. J Winter: Merck Spouse to J Winter: Epizyme, CVS/Caremark and Novartis. L Gordon: BMS and Calithera. J Lundin: Research funding from GSK and Novartis. A {\"O}sterborg: Research funding from Janssen, AstraZeneca, Beigene, Gilead and Loxo Inc. The other authors had nothing to disclose. Publisher Copyright: {\textcopyright} 2022 The Authors",

year = "2022",

month = nov,

doi = "10.1016/j.leukres.2022.106945",

language = "English (US)",

volume = "122",

journal = "Leukemia Research",

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T1 - Dual targeting fixed duration frontline monoclonal antibody therapy for chronic lymphocytic leukemia

T2 - A phase 2 study

AU - Ma, Shuo

AU - Rosen, Steven T.

AU - Winqvist, Maria

AU - Frankfurt, Olga

AU - Winter, Jane N.

AU - Gordon, Leo

AU - Helenowski, Irene

AU - Zhang, Hui

AU - Kreutzer, Jennifer

AU - Sönnert-Husa, Sonja

AU - Österborg, Anders

AU - Lundin, Jeanette

N1 - Funding Information: S Ma: Research funding from Abbvie, AstraZeneca, BeiGene, Juno, Loxo, Pharmacyclics, and TG Therapeutics; Consultancy/advisory role for Abbvie, AstraZeneca, BeiGene, Genentech, Pharmacyclics, TG Terapeutics, and Verastem; Speakers bureau participation for AstraZeneca, BeiGene, Janssen, and Pharmacyclics. J Winter: Merck Spouse to J Winter: Epizyme, CVS/Caremark and Novartis. L Gordon: BMS and Calithera. J Lundin: Research funding from GSK and Novartis. A Österborg: Research funding from Janssen, AstraZeneca, Beigene, Gilead and Loxo Inc. The other authors had nothing to disclose. Publisher Copyright: © 2022 The Authors

PY - 2022/11

Y1 - 2022/11

N2 - This phase 2 study describes long-term clinical and immunological effects of fixed-duration ofatumumab (anti-CD20) and alemtuzumab (anti-CD52) combination immunotherapy in 52 patients with previously untreated CLL. The median age was 65 years (range 45–79), 60% had Rai stage 3–4, 40% were IgHV unmutated and 25% had del(17p)/TP53 mutation. Alemtuzumab was given subcutaneously (30 mg tiw, 18 weeks) and ofatumumab intravenously (300–2000 mg) starting week 3 q2 weeks (8 doses). Overall response rate was 98% with 48% complete remissions including 60% bone marrow MRD-undetectable. After a median follow-up time of 68 months, the median PFS, TTNT, DOR and OS were 31, 62, 30 months and not reached, respectively. The estimated 5-year PFS, TTNT, DOR and OS were 35%, 51%, 35% and 87%, respectively. CD59 (complement-inhibitory molecule) was rapidly downregulated (p < 0.01) during the initial CD52 mAb run-in period. Our study demonstrated that dual targeting of CD20 and CD52 represents an early successful example of time-limited (4–5 months) chemotherapy-free precision therapy for previously untreated CLL.

AB - This phase 2 study describes long-term clinical and immunological effects of fixed-duration ofatumumab (anti-CD20) and alemtuzumab (anti-CD52) combination immunotherapy in 52 patients with previously untreated CLL. The median age was 65 years (range 45–79), 60% had Rai stage 3–4, 40% were IgHV unmutated and 25% had del(17p)/TP53 mutation. Alemtuzumab was given subcutaneously (30 mg tiw, 18 weeks) and ofatumumab intravenously (300–2000 mg) starting week 3 q2 weeks (8 doses). Overall response rate was 98% with 48% complete remissions including 60% bone marrow MRD-undetectable. After a median follow-up time of 68 months, the median PFS, TTNT, DOR and OS were 31, 62, 30 months and not reached, respectively. The estimated 5-year PFS, TTNT, DOR and OS were 35%, 51%, 35% and 87%, respectively. CD59 (complement-inhibitory molecule) was rapidly downregulated (p < 0.01) during the initial CD52 mAb run-in period. Our study demonstrated that dual targeting of CD20 and CD52 represents an early successful example of time-limited (4–5 months) chemotherapy-free precision therapy for previously untreated CLL.

KW - Alemtuzumab

KW - CLL

KW - Fixed duration

KW - Frontline treatment

KW - Immunotherapy

KW - Ofatumumab

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Dual targeting fixed duration frontline monoclonal antibody therapy for chronic lymphocytic leukemia: A phase 2 study

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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