Abstract
Background: MZL is the second most common lymphoma in older pts. Choosing an optimal treatment can be
challenging because of patient- or disease-related risk factors and treatment-related toxicities (Curr Opin Oncol.
2019;31(5):386-393). Zanubrutinib is a potent, irreversible next-generation Bruton tyrosine kinase (BTK) inhibitor
designed to maximize BTK occupancy and minimize off-target kinase inhibition, which may improve efficacy
outcomes and minimize toxicities, such as cardiac arrythmias and bleeding events. Zanubrutinib received accelerated
approval from the United States FDA for the treatment of pts with R/R MZL (Haematologica. 2022;107(1):35-43).
Aims: We aim to present a subgroup analysis of efficacy and safety of zanubrutinib in pts aged ≥65 years with R/R
MZL enrolled in MAGNOLIA (BGB-3111-214; NCT03846427).
Methods: MAGNOLIA is a phase 2, multicenter, single-arm study of adults with R/R MZL who had received ≥1 line
of therapy including ≥1 CD20-directed regimen. All were treated with zanubrutinib 160 mg twice daily until disease
progression or unacceptable toxicity. Use of long-term antiplatelet and anticoagulation agents was permitted. The
primary endpoint was overall response rate (ORR; complete response [CR] and partial response [PR]) determined by
an independent review committee (IRC) in accordance with the Lugano classification. Secondary endpoints include
ORR by investigator assessment (INV), duration of response (DOR), progression-free survival (PFS), and safety. All
pts gave informed consent.
Results: As of 18 January 2021, a total of 68 pts were enrolled (Table). Forty (61%) pts were ≥65 years old with a
median age of 73 (range, 65-85); 18 pts were ≥75 years old. Median number of prior therapies was 2 (range, 1-6) and
10 (25%) pts were refractory to last therapy. Most pts received prior rituximab + cyclophosphamide + vincristine + prednisone (48%) or bendamustine + rituximab (30%), while 5 (13%) pts received rituximab monotherapy. MZL
subtypes included extranodal (n=17, 43%), nodal (n=14, 35%), and splenic (n=8, 20%). Median duration of treatment
was 14.4 months (mo; range, 0.9-19.6). At a median follow-up of 15.8 mo (range, 2.8-21.8), ORR by IRC was 75%
(CR 25%, PR 50%; Table). Responses were observed in all subtypes, with an ORR of 71%, 86%, and 75% in extranodal, nodal, and splenic subtypes, respectively (CR 41%, 21%, and 0%, respectively). Median DOR and PFS
were not reached; 15-month PFS was 87% and 12-month DOR was 93%. Most (63%) pts are continuing
zanubrutinib. Treatment discontinuation due to disease progression was 28% by INV. Most common treatmentemergent adverse events (AEs) observed in ≥20% of pts include contusion (28%), diarrhea (25%), and constipation
(20%). Grade ≥3 neutropenia occurred in 5% of pts. The most common infection was upper respiratory tract
infection (10%). Two (5%) pts discontinued zanubrutinib due to unrelated fatal AEs (COVID-19 pneumonia and
myocardial infarction in a patient with pre-existing coronary artery disease). Atrial fibrillation/flutter and
hypertension occurred in 2 (5%) pts each and did not lead to treatment discontinuation. No pts required dose
reductions, or experienced major or serious hemorrhage.
Summary/Conclusion: The safety profile of zanubrutinib observed in older pts was consistent with previously published
results (Clin Cancer Res. 2021;27(23):6323-6332). Zanubrutinib was well tolerated and effective, as demonstrated by
a high response rate and durable disease control in older pts with R/R MZL.
challenging because of patient- or disease-related risk factors and treatment-related toxicities (Curr Opin Oncol.
2019;31(5):386-393). Zanubrutinib is a potent, irreversible next-generation Bruton tyrosine kinase (BTK) inhibitor
designed to maximize BTK occupancy and minimize off-target kinase inhibition, which may improve efficacy
outcomes and minimize toxicities, such as cardiac arrythmias and bleeding events. Zanubrutinib received accelerated
approval from the United States FDA for the treatment of pts with R/R MZL (Haematologica. 2022;107(1):35-43).
Aims: We aim to present a subgroup analysis of efficacy and safety of zanubrutinib in pts aged ≥65 years with R/R
MZL enrolled in MAGNOLIA (BGB-3111-214; NCT03846427).
Methods: MAGNOLIA is a phase 2, multicenter, single-arm study of adults with R/R MZL who had received ≥1 line
of therapy including ≥1 CD20-directed regimen. All were treated with zanubrutinib 160 mg twice daily until disease
progression or unacceptable toxicity. Use of long-term antiplatelet and anticoagulation agents was permitted. The
primary endpoint was overall response rate (ORR; complete response [CR] and partial response [PR]) determined by
an independent review committee (IRC) in accordance with the Lugano classification. Secondary endpoints include
ORR by investigator assessment (INV), duration of response (DOR), progression-free survival (PFS), and safety. All
pts gave informed consent.
Results: As of 18 January 2021, a total of 68 pts were enrolled (Table). Forty (61%) pts were ≥65 years old with a
median age of 73 (range, 65-85); 18 pts were ≥75 years old. Median number of prior therapies was 2 (range, 1-6) and
10 (25%) pts were refractory to last therapy. Most pts received prior rituximab + cyclophosphamide + vincristine + prednisone (48%) or bendamustine + rituximab (30%), while 5 (13%) pts received rituximab monotherapy. MZL
subtypes included extranodal (n=17, 43%), nodal (n=14, 35%), and splenic (n=8, 20%). Median duration of treatment
was 14.4 months (mo; range, 0.9-19.6). At a median follow-up of 15.8 mo (range, 2.8-21.8), ORR by IRC was 75%
(CR 25%, PR 50%; Table). Responses were observed in all subtypes, with an ORR of 71%, 86%, and 75% in extranodal, nodal, and splenic subtypes, respectively (CR 41%, 21%, and 0%, respectively). Median DOR and PFS
were not reached; 15-month PFS was 87% and 12-month DOR was 93%. Most (63%) pts are continuing
zanubrutinib. Treatment discontinuation due to disease progression was 28% by INV. Most common treatmentemergent adverse events (AEs) observed in ≥20% of pts include contusion (28%), diarrhea (25%), and constipation
(20%). Grade ≥3 neutropenia occurred in 5% of pts. The most common infection was upper respiratory tract
infection (10%). Two (5%) pts discontinued zanubrutinib due to unrelated fatal AEs (COVID-19 pneumonia and
myocardial infarction in a patient with pre-existing coronary artery disease). Atrial fibrillation/flutter and
hypertension occurred in 2 (5%) pts each and did not lead to treatment discontinuation. No pts required dose
reductions, or experienced major or serious hemorrhage.
Summary/Conclusion: The safety profile of zanubrutinib observed in older pts was consistent with previously published
results (Clin Cancer Res. 2021;27(23):6323-6332). Zanubrutinib was well tolerated and effective, as demonstrated by
a high response rate and durable disease control in older pts with R/R MZL.
| Original language | English |
|---|---|
| Article number | P1162 |
| Pages (from-to) | 2024-5 |
| Number of pages | 2 |
| Journal | HemaSphere |
| Publication status | Published - 15 Jun 2022 |
| Event | EHA 2022 Congress - Vienna Duration: 15 Jun 2022 → 17 Aug 2022 |
Research Beacons, Institutes and Platforms
- Manchester Cancer Research Centre
