Inhibition of Bruton tyrosine kinase (BTK) has transformed the treatment of chronic lymphocytic leukemia (CLL). While ibrutinib has led the way, zanubrutinib, a next-generation BTK inhibitor, has the potential to change treatment again.
Zanubrutinib improves outcomes and reduces toxicity because it minimizes off-target inhibition of TEC- and EGFR-family kinases, which is seen with ibrutinib, explained Peter Hillmen, PhD, MBChB, professor at the University of Leeds and honorary consultant hematologist at Leeds Teaching Hospitals NHS Trust.
Hillmen presented the interim results of the phase 3 ALPINE study during the Presidential Symposium at the European Hematology Association 2021 Virtual Congress (EHA2021 Virtual).
ALPINE is a global, randomized, phase 3 study comparing zanubrutinib with ibrutinib in patients with relapsed/refractory (R/R) CLL/small lymphocytic leukemia (SLL). In the preplanned interim analysis, the data cutoff occurred at 12 months after randomization of the first 415 patients.
The patients were randomized 1:1 to receive either zanubrutinib 160 mg twice a day (n = 207) or ibrutinib 420 mg once a day (n = 208). The baseline patient and disease characteristics were well balanced between the 2 arms, according to Hillmen.
The primary end point was overall response rate (ORR), defined as partial response (PR) plus complete response. Secondary end points were atrial fibrillation, duration of response, progression-
free survival (PFS), overall survival (OS), time to treatment failure, PR with lymphocytosis or higher, patient-reported outcomes, and safety. ORR was “definitely superior” for zanubrutinib, Hillmen said. The ORR for zanubrutinib was 78.3% (95% CI, 72.0%-83.7%) vs 62.5% (95% CI, 55.5%-69.1%)
for ibrutinib. The 12-month PFS was 94.9% for zanubrutinib vs 84.0% for ibrutinib. At 18 months, 20 patients on zanubrutinib had progressive disease compared with 42 patients on ibrutinib. OS wasn’t significantly different: 97.0% for zanubrutinib vs 92.07% for ibrutinib.
The majority of patients had an adverse event (AE), but zanubrutinib had fewer AEs leading to discontinuation (7.8% vs 13.0%) and fewer deaths due to AEs (3.9% vs 5.8%). Zanubrutinib had a slightly higher rate of neutropenia (28.4% vs 21.7%), but grade ≥3 infections were lower (12.7% vs 17.9%). The interim analysis also evaluated atrial fibrillation/flutter, which was a prespecified safety end point. The rate was significantly lower with zanubrutinib (2.5%) compared with ibrutinib (10.1%).
“These data support that more selective BTK inhibition, with more complete and sustained BTK occupancy, results in improved efficacy and safety outcomes than a less-specific BTK inhibitor,” Hillmen concluded.
In the Q&A, one attendee asked about comparing the results of ALPINE with ELEVATE-RR, which was presented a week earlier at the annual meeting of the American Society of Clinical Oncology. In that phase 3 trial comparing acalabrutinib with ibrutinib in patients with relapsed/refractory CLL, acalabrutinib had a noninferior PFS and significantly fewer events of atrial fibrillation.
Comparing the two is challenging for a number of reasons, though. Hillmen noted that the second-generation BTK inhibitors are not exactly the same as one another, so it wouldn’t be surprising to see differences in terms of toxicity or efficacy. In addition, ALPINE has interim data with a median duration of 15 months compared with ELEVATE-RR’s 3 years.
“We need to see more maturity in this trial to really compare,” Hillmen said. The ALPINE abstract was submitted to the meeting as a late-breaking abstract, so the data are still being analyzed.
However, one thing was apparent from both trials: “[T]he tolerability of the second-generation BTK inhibitors…is improved,” Hillmen said.¯
Hillmen P, Eichhorst B, Brown JR, et al. First interim analysis of ALPINE study: Results of a phase 3 randomized study of zanubrutinib vs ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma. Presented at: 2021 European Hematology Association Virtual Congress; June 9-17, 2021; Virtual. Abstract LB1900.
Building on positive results presented at last year’s American Society of Hematology annual meeting, a pair of studies presented at EHA2021 Virtual, this year’s annual meeting of the European Hematology Association, added heft to the advantages of zanubrutinib over other Bruton tyrosine kinase (BTK) inhibitors for several hematologic cancers.
Zanubrutinib is a second-generation BTK inhibitor known to have fewer off-target effects among both treatment-naïve and treatment-experienced patients. It is currently approved for use in patients with mantle cell lymphoma (MCL), while the FDA has accepted a supplemental new drug application (sNDA) for Waldenstrom macroglobulinemia²(WM) with a projected Prescription
Drug User Fee Act target date of October 18, 2021. In addition, zanubrutinib’s sNDA for its use among adults with marginal zone lymphoma (MZL) received a priority review designationin May.1
The first study,2 which took place in China, encompassed 91 patients with a median age of 61 years (range, 35-87) who had relapsed/refractory (R/R) chronic lymphocytic leukemia (n = 82) or small lymphocytic leukemia (n = 9) (CLL/SLL). Their most common poor prognostic indicators were unmutated IGHV gene (56.0%), del(17p) or TP53 mutation (24.2%), and del(11q) (22%). A high response rate was seen among those with del(17p) and/or TP53 mutation (91%; 95% CI, 70.8%-98.9%), while all with del(11q) responded (100%; 95% CI, 83.2%-100.0%). These results add to²data previously published²from the same trial, which demonstrated that zanubrutinib had a favorable benefit-risk profile.
In the present phase 2 study, patients received zanubrutinib 160 mg twice daily until disease progression or unacceptable toxicity. By the end of the follow-up period (median, 33.9 months; range, 0.8-41.4), 34.1% of patients had discontinued treatment because of progressive disease or adverse events. However, 65.9% remained on zanubrutinib.
Overall, 69.2%, 12.1%, and 6.6% had a partial response (PR), PR with lymphocytosis, or complete response, respectively; 3.3% each had stable or progressive disease or discontinued treatment before the first assessment; and 2.2% were not evaluable. In total, 87.9% (95% CI, 79.4%-93.8%) of the entire study cohort had a response.
With additional primary efficacy end points of duration of response (DOR) and progression-free survival (PFS), the authors’ analyses revealed:
• 24-month DOR: 83.4% (95% CI, 73.2%-90.0%)
• 36-month DOR: 69.9% (95% CI, 57.0%-79.6%)
• 24-month PFS: 85.0% (95% CI, 70.5%-87.4%)
• 36-month PFS: 68.1% (95% CI, 56.6%-77.4%)
The most common nonhematologic and hematologic adverse effects (AEs) were upper respiratory tract infection in 56.0% of patients and neutropenia in 78.0%, respectively.
Results of the second study,3²the BGB-3111-215 trial, support using zanubrutinib as a treatment option following previous treatment failure. These preliminary results were seen among 44 patients who received zanubrutinib (either 160 mg twice daily or 320 mg once daily) following intolerance to the first-generation BTK inhibitors ibrutinib (n = 39) or acalabrutinib (n = 1), with 4 patients having received both. Among this cohort, 34 had CLL, 6 had WM, and 2 each had MCL and MZL. Their median age was 70.5 years (range, 49.0-91.0), and all received at least 1 zanubrutinib dose post enrollment.
Data accumulated up to the November 1, 2020, cutoff showed that among the 44 patients, 43 were still on treatment. Among those who previously were on ibrutinib or acalabrutinib, 82.8% and 77.8%, respectively, did not have a recurrence of intolerant events, of which there were 87 with ibrutinib and 9 with acalabrutinib. This breaks down to a median 2 per patient (range, 1-5).
Among the patients who did have an intolerant event recur, the events were of a lower severity in 86.7% of previous-ibrutinib patients and 50% of previous-acalabrutinib patients.
Following administration of zanubrutinib in the patients, no deaths were reported. However, 77.3% did report an AE (myalgia, 20.5%; confusion, 18.2%; dizziness, 15.9%; fatigue, 15.9%; cough, 11.4%), 13.6% reported a grade >3 AE, and 2.3% reported a serious AE. In addition, 13.6% and 4.5% required dose interruption and dose reduction, respectively. No patients required treatment stoppage.
Overall, all patients with efficacy data available maintained response (38.5%) or had a deepening response (61.5%) to the newer BTK inhibitor. “Zanubrutinib provided an additional treatment option after intolerance to other BTK inhibitors,” the authors concluded, “demonstrating tolerability and sustained or improved efficacy.”
1. BeiGene announces U.S. FDA acceptance and priority review of supplemental new drug application for Brukinsa (zanubrutinib) in marginal zone lymphoma. News release. BeiGene; May 19, 2021. Accessed July 21, 2021.https://bit.ly/2SUcy0Y
2. Xu W, Yang S, Zhou K, et al. Zanubrutinib monotherapy in patients with relapsed or refractory chronic lymphocytic leukemia: 34-month follow-up results. Presented at: European Hematology Assocation Virtual Congress; June 9-17, 2021; abstract EP639. https://bit.ly/3zot751
3. Shadman M, Sharman JP, Levy MY, et al. Preliminary results of the phase 2 study of zanubrutinib in patients with previously treatment B-cell malignancies intolerant to ibrutinib and/or acalabrutinib. Presented at: European Hematology Assocation Virtual Congress; June 9-17, 2021; abstract EP642. https://bit.ly/3wQhiTz
An updated round of results from MAGNOLIA involving zanubrutinib in marginal zone lymphoma (MZL) was presented at the European Hematology Association 2021 Virtual Congress (EHA2021 Virtual). MAGNOLIA is a single-arm, multicenter, phase 2 study of adults with relapsed/refractory MZL who were previously treated with at least 1 prior line of therapy, including at least 1 CD20-directed regimen.1
In MAGNOLIA, patients are treated with 160 mg of zanubrutinib twice daily until disease progression or unacceptable toxicity. Use of long-term antiplatelet and anticoagulation agents is permitted. The primary end point is the overall response rate (ORR) as determined by an independent review committee. Secondary end points include ORR by investigator assessment, duration of response (DOR), progression-free survival (PFS), and safety.
Results through August 2020 presented at the American Society of Hematology in December 2020 showed that patients taking zanubrutinib, a Bruton tyrosine kinase (BTK) inhibitor, seemed to tolerate the drug better than earlier-generation BTK inhibitors, which allowed them to stay on the drug. The new round of results presented at EHA, which include data through January 11, 2021, include 68 patients enrolled and treated, with a median age of 70 years, including 28% who were 75 years or older.
MZL subtypes seen in the study included 38% of patients with extranodal MZL, 38% nodal, 18% splenic, and 6% indeterminate MZL. Patients in the study had received a median of 2 prior therapies, and 32% had disease that was refractory to their last therapy. Results presented at EHA showed:
Adverse events. Since the last round’s data cutoff, 2 patients in the study died from COVID-19 pneumonia and 1 patient who had preexisting coronary artery disease died from a heart attack. None of the deaths were considered related to zanubrutinib.
Of the 66 patients who could be evaluated, 28 (41%) stopped treatments, including 20 due to disease progression, 1 who withdrew consent, and 3 who required prohibited medications. Four stopped treatment due to adverse events (AEs), including the 2 who had COVID-19 pneumonia and the patient with the heart attack; the last one stopped due to pyrexia attributed to disease
The most common (≥10%) treatment-emergent AEs reported were diarrhea (22%), bruising (21%), constipation (15%), pyrexia (13%), abdominal pain (12%), upper respiratory tract infection (12%), back pain (10%), and nausea (10%). Most AEs were grade 1 or 2.
Phase 2 Results in Mantle Cell Lymphoma From Study in China
Long-term data from a phase 2 study in China evaluating zanubrutinib in patients with relapsed/refractory mantle cell lymphoma (MCL) were presented during the EHA2021 Virtual Congress. The study’s 86 patients had a median follow-up of 35.3 months, with data cutoff in September 2020.2
The patients, who were enrolled in 13 centers across China, had a median age of 60.5 years, and 83.7% were considered intermediate-to-high risk based on the International Prognostic Index Score. Most patients had advanced MCL, with 90.7% having stage III or higher; 45.3% had bone marrow involvement and 70.9% had extranodal disease. They had a median of 2 prior lines of therapy, and 52.3% had refractory disease.
Patients in the single-arm study were given 160 mg of zanubrutinib twice a day until disease progression or unacceptable toxicity. Responses were measured every 12 weeks until week 96, and then every 24 weeks. The ORR, PR rate, DOR, PFS, overall survival, and safety were assessed. Results were as follows:
• With a median follow-up of 35.3 months, 45.4% of patients remained on the study drug and 54.7% had stopped taking it, mostly due to disease progression (43.0%) or adverse events (9.3%).
• The ORR was 83.7%, and 67 patients (77.9%) achieved CR. Median DOR was not reached; 57.3% of the responders were estimated to be event-free—no disease progression or death—at 30 months.
• Median PFS was 33.0 months, and responses were generally consistent across all subgroups analyzed, including level of prior therapy and refractory status.
Adverse events. Consistent with earlier results, the treatment-related AEs that occurred most frequently, in at least 20% of the patients, were decreased neutrophil count (46.5%), upper respiratory tract infection (38.4%), rash (36.0%), decreased white blood cell count (33.7%), and decreased platelet count (32.6%). Most of these events were grade 1 or 2. The most common grade 3 events were decreased neutrophil count (18.6%) and pneumonia (12.8%).
Most of the AEs were seen during the initial treatment stage with zanubrutinib, and very few events were reported during the latest follow-up period.
1. Opat S, Tedeschi A, Linton K, et al. Phase 2 study of zanubrutinib in patients with relapsed/refractory marginal zone lymphoma (MAGNOLIA study). Presented at: European Hematology Assocation Virtual Congress; June 9-17, 2021; abstract EP783. https://bit.ly/3rCDZK0
2. Song Y, Zhou K, Zou D, et al. Zanubrutinib (ZANU) in patients (pts) with relapsed/refractory (R/R) mantle cell lymphoma (MCL): long-term efficacy and safety results from a phase 2 study. Presented at: European Hematology Assocation Virtual Congress; June 9-17, 2021; abstract EP789. https://bit.ly/3kZ4k3P
Treatment with zanubrutinib vs bendamustine-rituximab (BR) or dexamethasone-rituximab-cyclophosphamide (DRC) in patients with Waldenström macroglobulinemia (WM) has demonstrated longer survival, and zanubrutinib appears more cost-effective than ibrutinib, according to poster
presentations at the European Hematology Association 2021 Virtual Congress. WM is a rare, indolent, B-cell lymphoma that is generally treated with rituximab-based regimens or Bruton tyrosine kinase inhibitors.
To compare progression-free survival (PFS), overall survival (OS), and adverse events (AEs) among regimens, investigators used matching-adjusted indirect comparisons (MAICs) to match and compare data for 3 groups of patients with WM: 101 patients (83 relapsed/refractory, 19 treatment-naïve) treated with zanubrutinib in the ASPEN trial; 71 relapsed/refractory patients treated with
BR; and 72 treatment-naïve patients treated with DRC.1
MAICs carry the limitation of not being able to completely adjust for all unobserved and unreported baseline patient characteristics. Investigators said zanubrutinib vs DRC demonstrated significantly longer 12- and 24-month PFS (92% vs 85% and 90% vs 68%, respectively), longer 12-and 24-month OS (95% vs 92% and 94% and 85%), and a higher incidence of neutropenia (14.3% vs 9.7%). The postmatching HR for zanubrutinib PFS was 0.35 (95% CI, 0.14-0.86) and OS was 0.47 (95% CI, 0.14-1.62).
Zanubrutinib vs BR demonstrated significantly longer 12- and 24-month PFS (94% vs 79% and 81% vs 59%, respectively) and 12- and 24-month OS (98% vs 87% and 88% vs 77%), along with significantly lower incidence of neutropenia (17.5% vs 35.2%).
The postmatching HR for zanubrutinib vs BR PFS was 0.37 (95% CI, 0.15-0.91); for OS, it was 0.29 (95% CI, 0.10-0.85).
Investigators concluded that zanubrutinib appears to be cost-effective vs ibrutinib for US patients with WM who have received ≥1 prior therapy or as first-line treatment.2
They estimated savings based on life-years (LYs), quality-adjusted life-years (QALYs), and costs for each treatment over 30 years, basing OS, PFS, and time-to-discontinuation on data from the ASPEN trial. Costs considered included drug acquisition, management of AEs, and terminal care.
Findings demonstrated 0.94 LY and 0.84 QALY gained for patients treated with zanubrutinib vs ibrutinib and an incremental cost of $11,132 for zanubrutinib treatment, based on costs associated with extended treatment for zanubrutinib vs ibrutinib ($1,547,630 vs $1,536,498, respectively).
Total LYs for zanubrutinib vs ibrutinib were 11.33 vs 10.39, respectively, and¨total QALYs were 8.75 vs 7.90.
With its longer time to treatment failure and a lower monthly drug acquisition cost, zanubrutinib reduces costs of disease management by $2935 and other direct terminal costs by $2964 vs treatment with ibrutinib, the authors said. The incremental cost-effectiveness ratio for QALY gained was $13,205, according to the study. Investigators said that at a willingness-to-pay threshold of $100,000 per QALY gained, the probability of zanubrutinib being cost-effective was 61%. A limitation of this economic analysis was the immature survival data from ASPEN, the authors said.
1. Castillo J, Yang K, Liu R, et al. Efficacy and safety of zanubrutinib versus rituximab-based chemotherapy in Waldenström macroglobulinemia: matching-adjusted indirect comparisons. Presented at: European Hematology Assocation Virtual Congress; June 9-17, 2021; abstract EP805. https://bit.ly/3zKVbzJ
2. Castillo J, Yang K, Liu R, et al. Cost-effectiveness of zanubrutinib vs ibrutinib in adult patients with Waldenström macroglobulinemia. Presented at: European Hematology Assocation Virtual Congress; June 9-17, 2021; Abstract EP1174. https://bit.ly/3iTqjGL
Chimeric antigen receptor (CAR) T-cell therapy has revolutionized treatment for some hematological malignancies, and hundreds of trials are investigating CAR T-cell therapies in hematology and oncology. However, these therapies are complex to produce.
CAR-engineered natural killer (CAR NK) cells may be an alternative that compete with and complement CAR T-cell therapy, explained Ulrike Köhl, MD, PhD, during a plenary session at the European Hematology Association 2021 Virtual Congress (EHA2021 Virtual). She is a professor of immune oncology and director of the Institute for Clinical Immunology at the University of Leipzig, and director of the Fraunhofer Institute for Cellular Therapeutics and Immunology, both in Leipzig, Germany.
In the case of both CAR T cells and CAR NK cells, effector cells cannot recognize cancer cells to start killing them, but transduction of the respective effector cells results in a new receptor that is upregulated on the surface and binds to the cancer cell, killing it. The benefits of CAR T-cell therapies in diseases like acute lymphocytic leukemia (ALL) and diffuse large B-cell lymphoma have become well known. There are approximately 800 trials worldwide, Köhl said. “But we are also aware that manufacturing these autologous personalized CAR T cells is very complex,” Köhl said. The process includes stimulation, transduction, expansion, and formulation and takes about 12 days, on average, but it can take as long as 22 days.
Quality control is also challenging, and the CAR T-cell product can fail. Study results indicate that the product fails in somewhere between 1% and 12% of patients, and possibly in even up to 17% of patients.
“What’s the reason for that? [It’s that] these are heavily pretreated patients with a limited bone marrow function [and] less functional and [more] exhausted T cells,” Köhl explained. With NK cells, experience with allogeneic NK cell trials have shown a good graft vs leukemia effect without graft-vs-host disease (GVHD), Köhl said. A study of NK cell trials found that interleukin (IL)-2 stimulation led to improved NK cell cytotoxicity, but tumor immune escape was a disadvantage. Köhl gave the example of a child with acute myeloid leukemia (AML) in an early relapse state, who reached complete remission 1 month after NK cell application. “Unfortunately, this did not last very long, due to tumor immune escape mechanism,” she said. Trials that redirected NK cells showed improved results. For instance, in ALL, donor NK cells that were activated with cytokines against ALL cells killed 70% of the leukemic cells, and when the NK cells were redirected, they could completely eliminate ALL cells, according to Köhl.
Similar results were seen in AML, where activated NK cells had good activity against AML cells, but redirected CAR NK cells “killed much better.” Interest is growing in CAR NK cells, with 20 trials worldwide in 2019: Half were redirected against CD19 and the other half against different cancer epitopes. That number has risen to 35 in 2021.
The first-in-human trial in the United States led by Katy Rezvani, MD, PhD, at the University of Texas MD Anderson Cancer Center, tested CAR NK cells in patients with relapsed/refractory B lymphoid malignancies; the cells were redirected against CD19 and encoded with IL-15 for long-term persistence.1
The 11 participating patients had mostly good clinical outcomes: 8 patients had a response, 7 of whom experienced complete remission.
Rezvani and her colleagues postulated that a single cord-blood unit could produce more than 100 doses of CAR NK cells with which to treat patients. In addition to the good response, there was no cytokine release syndrome, no neurotoxicity, and no GVHD.
Given the results seen with CAR NK cells, could they compete with CAR T-cell therapy? The answer isn’t simple, Köhl believes. “We need both,” she said. “They clearly have also different roles.” CAR NK
cells, for instance, may possibly be used as a bridge to transplantation.
Liu E, Marin D, Banarjee P, et al. Use of CAR-transduced natural killer cells in CD19-positive lymphoid tumors.N Engl J Med. 2020;382(6):545-553. doi:10.1056/NEJMoa1910607
Celltrion Healthcare released new real-world data demonstrating the clinical effectiveness of its biosimilar rituximab (Truxima; CT-P10) in patients with diffuse large B-cell lymphoma (DLBCL) at the European Hematology Association 2021 Virtual Congress (EHA2021 Virtual).
Truxima received marketing authorization from the European Medicines Agency in 2017 for the treatment of rheumatoid arthritis and certain blood cancers, including DLBCL. The most common subtype of non-Hodgkin lymphoma (NHL), DLBCL represents an estimated 30% to 40% of adult cases. Truxima was the first rituximab biosimilar approved in the United States, launchingon the
US market in 2019 in partnership with Teva Pharmaceutical Industries.
Celltrion ran a noninterventional postauthorization safety study in which researchers collected patient data from hospital medical records for 382 patients with DLBCL who received CT-P10 therapy in the United Kingdom, Spain, France, Germany, or Italy. Treatment pattern data were retrospectively collected during a 30-month observation period.
“This is the first multicountry retrospective postapproval study to investigate the effectiveness and safety of CT-P10 treatment in patients with DLBCL in a real-world setting across Europe,” said Mark Bishton, PhD, consultant hematologist and honorary clinical associate professor at the University of Nottingham School of Medicine in the United Kingdom, in a statement.
The results met the primary end points of overall survival, progression-free survival, and summary of best responses. Thirty months after receiving their first dose of CT-P10, 67% (95% CI, 61.3%-72.1%) of patients had not experienced disease progression, and the overall survival was 74% (95% CI, 69.2%-79.1%). Additionally, 82% (n = 312) of patients achieved a complete response and 12% (n = 46) achieved a partial response 30 months post index. Only 4% (n = 16) experienced no response and 2% (n = 8) experienced disease progression. Secondary end points for CT-P10’s safety profile and treatment pathways were also examined. Patients generally found CT-P10 to be tolerable, and the number of adverse events reported was comparable with that reported for the
reference product (Rituxan).
Celltrion also released real-world data on rapid infusion of CT-P10 in 192 patients with NHL and chronic lymphocytic leukemia (CLL) at the EHA updates-in-Hematology. Typically, infusion of rituximab in Europe is conducted through a slow initial infusion rate with a gradual upward titration. Rapid infusion is often reserved for when patients receive subsequent infusions after experiencing no serious complications after the first dose.
This was the first multicountry study to report real-world evidence evaluating the safety and efficacy of rapid infusion of CT-P10. The results showed that rapid infusion of the biosimilar was well tolerated, with only 10% (n = 20; 95% CI, 6.0%-15.0%) of patients reporting an infusion-related reaction (IRR). Overall, 96% of the reported reactions were grade 1 or 2. Among the 20 patients who experienced IRRs, the most common were fatigue (35%; n = 7), nausea (30%; n = 6), and vomiting (15%; n = 3).
At the end of the 6-month observation period, 74% of patients (n = 142) achieved a complete response and 22% (n = 42) achieved a partial response. We are encouraged by the results of the study, [because] Truxima has demonstrated a similar IRR rate to reference rituximab. This will allow
informed, evidence-based decisions on cost-effective treatment strategy for patients with CLL or NHL,” said HoUng Kim, PhD, head of the medical and marketing division at Celltrion, in an earlier interview.
Celltrion Healthcare presents the first real-world data for Truxima (biosimilar rituximab) in patients with diffuse large B-cell lymphoma at the EHA 2021 Virtual Congress. News release. Celltrion; June 12, 2021. Accessed July 21, 2021. https://bwnews.pr/2Ux1KHn