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Clinical Trial
. 2024 Nov 26;8(22):5855-5863.
doi: 10.1182/bloodadvances.2024013277.

Magrolimab plus rituximab in relapsed/refractory indolent non-Hodgkin lymphoma: 3-year follow-up of a phase 1/2 trial

Amitkumar Mehta  1 , Leslie Popplewell  2 , Graham P Collins  3 , Sonali M Smith  4 , Ian W Flinn  5 , Nancy L Bartlett  6 , Nilanjan Ghosh  7 , Gal Hacohen-Kleiman  8 , Yanan Huo  8 , Linda Su-Feher  8 , Camille Renard  8 , Ranjana Advani  9 , Mark Roschewski  10
Affiliations
Clinical Trial

Magrolimab plus rituximab in relapsed/refractory indolent non-Hodgkin lymphoma: 3-year follow-up of a phase 1/2 trial

Amitkumar Mehta et al. Blood Adv. .

Abstract

Relapsed/refractory (R/R) indolent non-Hodgkin lymphoma (iNHL) is generally considered incurable with current treatment options. Previous phase 1b/2 results showed combining magrolimab (anti-cluster-of-differentiation [CD] 47 antibody) with the anti-CD20 antibody rituximab (M+R) has antitumor activity against R/R iNHL. We report 3-year follow-up data from this phase 1b/2 study assessing long-term safety and efficacy of M+R in R/R iNHL. After magrolimab priming, 4 patient groups in phase 1b M+R received 10 to 45-mg/kg magrolimab doses with 375 mg/m2 rituximab. Phase 2 explored 30 and 45 mg/kg magrolimab. Primary end points were treatment-emergent adverse events (TEAEs) and objective response rate (ORR). Secondary end points included duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Exploratory analysis included circulating tumor DNA, biomarkers of magrolimab tumor penetration, and drug target expression assessments. Of 46 patients treated in phase 1b/2, 42 had follicular lymphoma and 4 had marginal zone lymphoma. All patients experienced ≥1 any-grade TEAE, and 44 reported ≥1 treatment-related TEAE. No additional toxicities were reported during long-term follow-up, and there were no treatment-related deaths. Median follow-up was 36.7 (range, 1.2-62.3) months. The ORR was 52.2%, with 30.4% achieving a complete response. The median DOR was 15.9 months, and median time-to-response was 1.8 months. Median PFS and OS were 7.4 (95% confidence interval, 4.8-13.0) months and not reached, respectively. These results demonstrate the long-term safety and efficacy of M+R in patients with iNHL and support further exploration of CD47-based treatment combinations. This trial was registered at www.ClinicalTrials.gov as #NCT02953509.

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Conflict of interest statement

Conflict-of-interest disclosure: A.M. reports consultancy for AstraZeneca, BeiGene, Bristol Myers Squibb, Gilead Sciences, Inc, Incyte Corporation, Kyowa Kirin, MorphoSys/Incyte Corporation, Novartis, Pharmacyclics, Seattle Genetics, and TG Therapeutics Inc; reports research funding from Affimed, Celgene/Bristol Myers Squibb, Forty Seven, Inc/Gilead Sciences, Inc, I-MAB Biopharma, Incyte Corporation, Innate Pharmaceuticals, Juno Pharmaceuticals/Bristol Myers Squibb, Kite Pharma/Gilead Sciences, Merck, Roche/Genentech, Seattle Genetics, Takeda, and TG Therapeutics; and reports speakers bureau participation for AstraZeneca, BeiGene, Bristol Myers Squibb, Gilead Sciences, Inc, Kyowa Kirin, Incyte Corporation, MorphoSys/Incyte, Pharmacyclics, and Seattle Genetics. L.P. reports honoraria from Pfizer and Roche; and reports travel support from Novartis. G.P.C. has received honoraria for speaker or consultancy work from Roche, Takeda, Kite Pharma/Gilead Sciences, Incyte, AstraZeneca, BeiGene, Novartis, SecuraBio, and AbbVie; and received research funding from Pfizer, BeiGene, AstraZeneca, Amgen, Inc, and Bristol Myers Squibb. S.M.S. reports consultancy for MorphoSys/Incyte, Janssen, Bristol Myers Squibb, Karyopharm, TG Therapeutics, and Celgene; and received research funding from FortySeven, TG Therapeutics, Pharmacyclics, Acerta, Karyopharm, Portola, Celgene, Novartis, Roche/Genentech, and Epizyme. I.W.F. reports consultancy for AbbVie, AstraZeneca, BeiGene, Century Therapeutics, Genentech, Inc, Genmab, Hutchison MediPharma, Iksuda Therapeutics, InnoCare Pharma, Janssen, Kite Pharma, MorphoSys, Myeloid Therapeutics, Novartis, Nurix Therapeutics, Pharmacyclics, F. Hoffmann-La Roche Ltd, Secura Bio, Servier Pharmaceuticals, Takeda, TG Therapeutics Inc, Verastem, Vincerx Pharma, and Xencor; and reports institutional research grants from AbbVie, Acerta Pharma, Agios, ArQule, AstraZeneca, BeiGene, Biopath, Bristol Myers Squibb, Calibr, Cancer and Leukemia Group B, Celgene, City of Hope National Medical Center, Constellation Pharmaceuticals, Curis, CTI Biopharma, Epizyme, Fate Therapeutics, Forma Therapeutics, Forty Seven, Genentech, Inc, Gilead Sciences, Inc, InnoCare Pharma, IGM Biosciences, Incyte, Infinity Pharmaceuticals, Janssen, Kite Pharma, Loxo, Merck, Millennium Pharmaceuticals, MorphoSys, Myeloid Therapeutics, Novartis, Nurix, Pfizer, Pharmacyclics, Portola Pharmaceuticals, Rhizen Pharmaceuticals, F. Hoffmann-La Roche Ltd, Seattle Genetics, Tessa Therapeutics, TCR2 Therapeutics, TG Therapeutics, Trillium Therapeutics, Triphase Research and Development Corporation, Unum Therapeutics, and Verastem. N.L.B. reports research funding from ADC Therapeutics, Autolus, Bristol Myers Squibb, Celgene, Forty Seven, Janssen, Kite Pharma, Merck, Millennium, Pharmacyclics, F. Hoffmann-La Roche/Genentech, and Seattle Genetics; and reports board of directors membership or advisory committee membership for ADC Therapeutics, F. Hoffmann-La Roche/Genentech, and Seattle Genetics. N.G. has received consulting fees from Seagen, TG Therapeutics, AstraZeneca, Pharmacyclics, Janssen, Bristol Myers Squibb, Gilead Sciences, Inc, Kite Pharma, Syncopation, Lava Therapeutics, BeiGene, Incyte, Karyopharm, Roche/Genentech, Novartis, Loxo Oncology, Genmab, Adaptive Biotech, and ADC Therapeutics; previously served on speakers bureau for Gilead Sciences, Inc, AstraZeneca, Bristol Myers Squibb, Pharmacyclics, Janssen, Epizyme; and has received research funding from TG Therapeutics, Roche/Genentech, Bristol Myers Squibb, Gilead Sciences, Inc, MorphoSys, and AbbVie. G.H.-K. and Y.H. are employed by Gilead Sciences, Inc, and hold stock in Gilead Sciences, Inc. L.S.-F. is employed by, and holds stock in, Gilead Sciences, Inc. C.R., at the time of the study, was employed by Gilead Sciences, Inc, and held stock in Gilead Sciences, Inc and Alphabet Inc, Class A. R.A. has received research funding from BeiGene, Merck, Roche/Genentech, Seattle Genetics, ADC Therapeutics, Pharmacyclics, Cyteir, and Daiichi Sankyo; and has served on advisory boards for Roche/Genentech, MorphoSys, and Epizyme. M.R. declares no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Any-grade TEAEs in ≥15% of patients.
Figure 2.
Figure 2.
Responses over time. NA, not available; SD, stable disease.
Figure 3.
Figure 3.
DOR. NE, not estimable.
Figure 4.
Figure 4.
Survival. (A) PFS. (B) OS. NE, not estimable.
See this image and copyright information in PMC

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