Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jun 16;207(2):612-618.
doi: 10.1111/bjh.20219. Online ahead of print.

The anti-CD47 antibody magrolimab with obinutuzumab and venetoclax in relapsed or refractory indolent B-cell lymphomas

Rahul Lakhotia  1 , Christopher Melani  1 , Stefania Pittaluga  2 , Max J Gordon  1 , James D Phelan  1 , Jagan R Muppidi  1 , Atekelt Tadese  1 , Sarah Evans  1 , Elaine S Jaffe  2 , Louis M Staudt  1 , Wyndham H Wilson  1 , Mark Roschewski  1
Affiliations

The anti-CD47 antibody magrolimab with obinutuzumab and venetoclax in relapsed or refractory indolent B-cell lymphomas

Rahul Lakhotia et al. Br J Haematol. .

Abstract

Follicular lymphoma (FL), marginal zone lymphoma (MZL), chronic lymphocytic leukaemia (CLL) and mantle cell lymphoma (MCL) are characterized by a continuous incidence of relapse and increasing resistance to therapy. Novel immunotherapy approaches are needed. Magrolimab, a CD47-blocking antibody, disrupts CD47:SIRPα-mediated antiphagocytic signalling. When combined with a prophagocytic signal from an anti-CD20 antibody rituximab, it has shown activity in relapsed or refractory FL and MZL. In this phase 1 study, adding the BCL2-inhibitor venetoclax to magrolimab and the anti-CD20 antibody obinutuzumab resulted in complete responses in 6 of 10 (60%) evaluable patients with FL, MZL or CLL. Notably, we did not observe increased risk of infections previously reported from studies of magrolimab in acute myeloid leukaemia and higher risk myelodysplastic syndromes.

Keywords: CD47; chronic lymphocytic leukemia; follicular lymphoma; immunotherapy; magrolimab; marginal zone lymphoma.

PubMed Disclaimer

Conflict of interest statement

The authors report no conflict of interest.

Figures

FIGURE 1
FIGURE 1
Pathways targeted and adverse events. (A) Malignant B‐cell survival pathways targeted by combination of magrolimab, obinutuzumab and venetoclax. Magrolimab blocks the CD47‐mediated antiphagocytic signalling and obinutuzumab provides a potent prophagocytic signal by stimulating antibody‐dependent cellular phagocytosis. Venetoclax induces apoptosis through inhibition of BCL2 and enhances anti‐CD20‐mediated antibody‐dependent phagocytosis (B) All treatment‐emergent adverse events (AEs) in >1 patient and all grade ≥3 AEs plotted as a percentage of affected patients. The numbers within the stacked bars reflect the number of affected patients.
FIGURE 2
FIGURE 2
Objective responses and survival outcomes for all patients. (A) Best objective tumour responses in all patients divided by histological subtype compared to baseline. (B) Swimmer's plot demonstrating timing and duration of responses in all patients divided by histological subtype, along with details of prior therapy. (C) Duration of complete response (DOCR) and duration of partial response (DOPR). (D) Progression‐free survival and overall survival for all patients. CI, confidence interval; CLL, chronic lymphocytic leukaemia; CR, complete response; FL, follicular lymphoma; MCL, mantle cell lymphoma; MZL, marginal zone lymphoma; PR, partial response; SPD, sum of product of diameters on computed tomography scan.
See this image and copyright information in PMC

References

    1. Kanters S, Ball G, Kahl B, Wiesinger A, Limbrick‐Oldfield EH, Sudhindra A, et al. Clinical outcomes in patients relapsed/refractory after >/=2 prior lines of therapy for follicular lymphoma: a systematic literature review and meta‐analysis. BMC Cancer. 2023;23(1):74. - PMC - PubMed
    1. Leonard JP, Trneny M, Izutsu K, Fowler NH, Hong X, Zhu J, et al. AUGMENT: a phase III study of Lenalidomide plus rituximab versus placebo plus rituximab in relapsed or refractory indolent lymphoma. J Clin Oncol. 2019;37(14):1188–1199. - PMC - PubMed
    1. Stanchina MD, Montoya S, Danilov AV, Castillo JJ, Alencar AJ, Chavez JC, et al. Navigating the changing landscape of BTK‐targeted therapies for B cell lymphomas and chronic lymphocytic leukaemia. Nat Rev Clin Oncol. 2024;21(12):867–887. - PubMed
    1. Crombie JL, Graff T, Falchi L, Karimi YH, Bannerji R, Nastoupil L, et al. Consensus recommendations on the management of toxicity associated with CD3xCD20 bispecific antibody therapy. Blood. 2024;143(16):1565–1575. - PubMed
    1. Santomasso BD, Nastoupil LJ, Adkins S, Lacchetti C, Schneider BJ, Anadkat M, et al. Management of immune‐related adverse events in patients treated with chimeric antigen receptor T‐cell therapy: ASCO guideline. J Clin Oncol. 2021;39(35):3978–3992. - PubMed