TY - JOUR
T1 - Magrolimab plus rituximab in relapsed/refractory indolent non-Hodgkin lymphoma
T2 - 3-year follow-up of a phase 1/2 trial
AU - Mehta, Amitkumar
AU - Popplewell, Leslie
AU - Collins, Graham P.
AU - Smith, Sonali M.
AU - Flinn, Ian W.
AU - Bartlett, Nancy L.
AU - Ghosh, Nilanjan
AU - Hacohen-Kleiman, Gal
AU - Huo, Yanan
AU - Su-Feher, Linda
AU - Renard, Camille
AU - Advani, Ranjana
AU - Roschewski, Mark
N1 - Publisher Copyright:
© 2024 American Society of Hematology. All rights reserved.
PY - 2024/11/26
Y1 - 2024/11/26
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85210948160&partnerID=8YFLogxK
U2 - 10.1182/bloodadvances.2024013277
DO - 10.1182/bloodadvances.2024013277
M3 - Article
C2 - 39213421
AN - SCOPUS:85210948160
SN - 2473-9529
VL - 8
SP - 5855
EP - 5863
JO - Blood Advances
JF - Blood Advances
IS - 22
ER -