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1. Outcomes in high-risk subgroups after fixed-duration ibrutinib + venetoclax for chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL): Up to 5.5 years of follow-up in the phase 2 CAPTIVATE study.

Author

Wierda, William G, Jacobs, Ryan, Barr, Paul M, Allan, John N, Siddiqi, Tanya, Tedeschi, Alessandra, Kipps, Thomas J, O'Brien, Susan Mary, Badoux, Xavier C, Visentin, Andrea, Lasica, Masa, Carney, Dennis, Elinder Camburn, Anna, De La Serna Torroba, Javier, Szafer-Glusman, Edith, Zhou, Cathy, Szoke, Anita, Dean, James P, Ghia, Paolo, and Tam, Constantine S

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Clinical Research, Lymphoma, Biotechnology, Cancer Genomics, Hematology, Precision Medicine, Genetics, Cancer, Clinical Trials and Supportive Activities, Lymphatic Research, Minority Health, Rare Diseases, Human Genome, 6.1 Pharmaceuticals, Clinical Sciences, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

7009 Background: The phase 2 CAPTIVATE study evaluated first-line ibrutinib (Ibr) + venetoclax (Ven) for CLL/SLL in 2 cohorts: minimal residual disease (MRD)-guided randomized discontinuation (MRD cohort) and Fixed Duration (FD cohort). Ibr±Ven retreatment was allowed in patients (pts) who had progressive disease (PD). Here, we report outcomes for pts with high-risk genomic features from the FD cohort and retreatment outcomes in pts from the FD cohort and MRD cohort placebo arm. Methods: Pts aged ≤70 y with previously untreated CLL/SLL without restriction on genomic risk factors received 3 cycles of Ibr, then 12 cycles of Ibr+Ven (Ibr, 420 mg/d orally; Ven, 5-wk ramp up to 400 mg/d orally). On-study retreatment included single-agent Ibr (FD cohort or MRD cohort placebo arm); pts with PD >2 y after end of treatment (EOT) could be retreated with FD Ibr+Ven (FD cohort). Results: In the FD cohort (n=159) with a median follow-up of 61.2 mo (range, 0.8–66.3), 5-y PFS and OS rates (95% CI) were 67% (59–74) and 96% (91–98), respectively. 5-y PFS rates were higher in pts with undetectable MRD at 3 mo after EOT in peripheral blood (83%) or bone marrow (84%) vs those without (48% and 50%, respectively). 5-y PFS rates (95% CI) in pts with genomic risk factors were: del(17p)/mutated TP53 41% (21–59), complex karyotype 57% (37–72), del(11q) 64% (30–85), and unmutated IGHV 68% (50–80) (Table). In total, 18 second malignancies occurred in 13 pts (10 events in 8 pts during FD Ibr+Ven, 6 events in 4 pts after EOT and before retreatment, and 2 events in 2 pts during retreatment). Of 202 pts who completed Ibr+Ven (FD cohort, n=159; MRD cohort placebo arm, n=43), 63 have had PD to date; PD occurred >2 y after EOT in 43/63 pts (68%). 32/63 (51%) pts initiated retreatment with Ibr (n=25) or Ibr+Ven (n=7). With a median time on Ibr retreatment of 21.9 mo (range, 0.03–50.4), ORR was 86% in 22 evaluable pts (best response: 1 CR; 1 nodular PR; 17 PR; 2 SD; 1 PD [Richter transformation]). With a median time on Ibr+Ven retreatment of 13.8 mo (range, 3.7–15.1), ORR was 71% in 7 evaluable pts (best response: 1 CR; 4 PR; 1 PR with lymphocytosis; 1 SD). Conclusions: With up to 5.5 y of follow-up, FD Ibr+Ven continues to provide clinically meaningful PFS in pts with high-risk genomic features, as well as in the overall population. Ibr-based retreatment provides promising responses in pts needing subsequent therapy after the all-oral FD regimen of Ibr+Ven. Clinical trial information: NCT02910583 . [Table: see text]

Published
2024

2. Cardiovascular events reported in patients with B-cell malignancies treated with zanubrutinib.

Author

Moslehi, Javid, Furman, Richard, Tam, Constantine, Salem, Joe-Elie, Flowers, Christopher, Cohen, Aileen, Zhang, Meng, Zhang, Jun, Chen, Lipeng, Ma, Han, and Brown, Jennifer

Subjects
Humans, Pyrimidines, Pyrazoles, Piperidines, Male, Aged, Female, Protein Kinase Inhibitors, Middle Aged, Cardiovascular Diseases, Adenine, Agammaglobulinaemia Tyrosine Kinase, Incidence, Atrial Fibrillation, Aged, 80 and over
Abstract

First-generation Bruton tyrosine kinase (BTK) inhibitor, ibrutinib, has been associated with an increased risk of cardiovascular toxicities. Zanubrutinib is a more selective, next-generation BTK inhibitor. In this analysis, incidence rates of atrial fibrillation, symptomatic (grade ≥2) ventricular arrhythmia, and hypertension were evaluated in a pooled analysis of 10 clinical studies with zanubrutinib monotherapy in patients (N = 1550) with B-cell malignancies and a pooled analysis of head-to-head studies comparing zanubrutinib with ibrutinib (ASPEN cohort 1; ALPINE). Among the 10 studies, most patients (median age, 67 years) were male (66.3%) and had CLL/SLL (60.5%). Overall incidence and exposure-adjusted incidence rates (EAIR) for atrial fibrillation, symptomatic ventricular arrhythmia, and hypertension were lower with zanubrutinib than ibrutinib. Despite a similar prevalence of preexisting cardiovascular events in ASPEN and ALPINE, atrial fibrillation/flutter incidence rates (6.1% vs 15.6%) and EAIR (0.2 vs 0.64 persons per 100 person-months; P < .0001) were lower with zanubrutinib than with ibrutinib. Symptomatic ventricular arrhythmia incidence was low for both zanubrutinib (0.7%) and ibrutinib (1.7%) with numerically lower EAIR (0.02 vs 0.06 persons per 100 person-months, respectively) for zanubrutinib. The hypertension EAIR was lower with zanubrutinib than ibrutinib in ASPEN but similar between treatment arms in ALPINE. The higher hypertension EAIR in ALPINE was inconsistent with other zanubrutinib studies. However, fewer discontinuations (1 vs 14) and deaths (0 vs 6) due to cardiac disorders occurred with zanubrutinib versus ibrutinib in ALPINE. These data support zanubrutinib as a treatment option with improved cardiovascular tolerability compared with ibrutinib for patients with B-cell malignancies in need of BTK inhibitors. These trials were registered at www.ClinicalTrials.gov as # NCT03053440, NCT03336333, NCT03734016, NCT04170283, NCT03206918, NCT03206970, NCT03332173, NCT03846427, NCT02343120, and NCT03189524.

Published
2024

4. Relapse after First-Line Fixed Duration Ibrutinib + Venetoclax: High Response Rates to Ibrutinib Retreatment and Absence of BTK Mutations in Patients with Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) with up to 5 Years of Follow-up in the Phase 2 Captivate Study

Author

Ghia, Paolo, Wierda, William G, Barr, Paul M, Kipps, Thomas J, Siddiqi, Tanya, Allan, John N, Hunter, Zoë, Zhou, Cathy, Szoke, Anita, Dean, James P, and Tam, Constantine S

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Oncology and Carcinogenesis, Cancer, Clinical Research, Precision Medicine, Rare Diseases, Lymphatic Research, Hematology, Lymphoma, Orphan Drug, Clinical Trials and Supportive Activities, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Paediatrics and Reproductive Medicine, Immunology, Biochemistry and cell biology, Cardiovascular medicine and haematology, Paediatrics
Abstract

Background: CAPTIVATE (PCYC-1142) is a multicenter phase 2 study of ibrutinib + venetoclax as first-line treatment for CLL/SLL in 2 cohorts: minimal residual disease (MRD)-guided randomized-discontinuation (MRD cohort) and Fixed Duration (FD cohort). Results from the FD cohort with 4 years of follow-up (Barr, ASCO 2023) showed 4-year progression-free survival (PFS) and overall survival (OS) rates of 79% and 98%, respectively. After completing fixed-duration treatment, ibrutinib-based retreatment was allowed per protocol in patients with an indication for treatment after experiencing progressive disease (PD). Here, we report retreatment outcomes in patients from the FD cohort or the MRD cohort placebo arm, as well as updated results with an additional year of follow-up (up to 5 years) from the FD cohort. Methods: Patients aged ≤70 years with previously untreated CLL/SLL received 3 cycles of ibrutinib, then 12 cycles of combined ibrutinib + venetoclax (ibrutinib, 420 mg/day orally; venetoclax, standard 5-week ramp up to 400 mg/day orally). Response was assessed by investigators per International Workshop on CLL (iwCLL) 2008 criteria. Duration of response (DOR), PFS, and OS were estimated using Kaplan-Meier methodology. Per protocol, on-study retreatment included single-agent ibrutinib; patients with PD >2 years after treatment completion could be retreated with the FD regimen (3 cycles of ibrutinib + 12 cycles of ibrutinib + venetoclax). Results: Of 202 patients treated with fixed-duration ibrutinib + venetoclax in the FD cohort (n=159) or the MRD cohort placebo arm (n=43), 53 have had PD to date (Table 1), with PD occurring >2 years after completion of treatment in the majority of patients (33/53 [62%]). Of the 40 patients with available samples at PD, one had an acquired resistance-associated mutation in BCL2 (A113G); no other patient had clinically relevant mutations in BTK, BCL2, or PLCG2. A total of 22 patients have initiated retreatment on study with single-agent ibrutinib. With a median time on retreatment of 17 months (range, 0-45), overall response rate (ORR) in 21 evaluable patients was 86% (with best responses of complete response [CR], n=1 [5%]; partial response [PR], n=17 [81%]; PR with lymphocytosis, n=1 [5%]; stable disease, n=1 [5%]; PD [Richter transformation], n=1 [5%]). The most frequent adverse events (AEs; occurrence ≥10%) during single-agent ibrutinib retreatment were COVID-19 (n=6, all grade 1/2), diarrhea (n=5), hypertension (n=4), and pyrexia (n=3). No dose reductions or discontinuations due to AEs occurred among retreated patients. Eighteen patients have not received subsequent treatment, 7 patients have initiated other subsequent therapies, and 6 patients have started retreatment with ibrutinib + venetoclax (time on retreatment, 5-15 months). Best responses in patients retreated with ibrutinib + venetoclax are CR, n=2; PR, n=3; and SD, n=1. Response data for the patient with BCL2 (A113G) is pending. To date, with a median time on study of 56 months (range, 1-61) for patients in the FD cohort, the 54-month PFS and OS rates were 70% (95% CI, 62-77) and 97% (95% CI, 93-99), respectively. Best response rates remained unchanged from the 4-year follow-up analysis (CR, including CR with incomplete bone marrow recovery [CRi], 58%; ORR, 96%). In patients who achieved CR/CRi (n=92), median duration of CR/CRi was not reached; 90/92 patients (98%) achieved durable CR/CRi (lasting ≥12 cycles). PFS in patients with high-risk features was promising (Table 2), but it was numerically lower in the subset with del(17p)/mutated TP53 (54-month rate, 45% [95% CI, 25-64]). Serious AEs considered related to study treatment and second malignancies continued to be collected after completion of fixed-duration treatment. One AE of basal cell carcinoma occurred during this additional year of follow-up. In total, second malignancies have occurred in 8% of patients since completion of ibrutinib + venetoclax treatment. Conclusion: Ibrutinib-based retreatment results in the CAPTIVATE study show promising responses in patients needing subsequent therapy after receiving this all-oral, once-daily fixed-duration regimen for first-line treatment of CLL/SLL. With up to 5 years of follow-up, fixed-duration ibrutinib + venetoclax continues to provide deep remissions with clinically meaningful PFS, including in patients with high-risk genomic features.

Published
2023

5. Zanubrutinib Versus Bendamustine and Rituximab in Patients With Treatment-Naïve Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: Median 5-Year Follow-Up of SEQUOIA

Author

Shadman, Mazyar, Munir, Talha, Robak, Tadeusz, Brown, Jennifer R., Kahl, Brad S., Ghia, Paolo, Giannopoulos, Krzysztof, Šimkovič, Martin, Österborg, Anders, Laurenti, Luca, Walker, Patricia A., Opat, Stephen S., Ciepluch, Hanna, Greil, Richard, Hanna, Merit, Tani, Monica, Trněný, Marek, Brander, Danielle, Flinn, Ian W., Grosicki, Sebastian, Verner, Emma, Tedeschi, Alessandra, de Guibert, Sophie, Tumyan, Gayane, Laribi, Kamel, García-Marco, José A., Li, Jian-Yong, Tian, Tian, Liu, Yu, Korolkiewicz, Roman, Szeto, Andy, Tam, Constantine S., and Jurczak, Wojciech

Published
2024
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6. Immune restoration with ibrutinib plus venetoclax in first-line chronic lymphocytic leukemia: the phase 2 CAPTIVATE study.

Author

Moreno, Carol, Solman, Isabelle, Tam, Constantine, Grigg, Andrew, Scarfò, Lydia, Srinivasan, Srimathi, Mali, Raghuveer, Zhou, Cathy, Dean, James, Szafer-Glusman, Edith, Kipps, Thomas, and Choi, Michael

Subjects
Humans, Leukemia, Lymphocytic, Chronic, B-Cell, Immune Reconstitution, Piperidines
Abstract

We evaluated immune cell subsets in patients with chronic lymphocytic leukemia (CLL) who received first-line therapy with 3 cycles of ibrutinib then 13 cycles of ibrutinib plus venetoclax in the minimal residual disease (MRD) cohort of the CAPTIVATE study (NCT02910583). Patients with Confirmed undetectable MRD (uMRD) were randomly assigned to placebo or ibrutinib groups; patients without Confirmed uMRD were randomly assigned to ibrutinib or ibrutinib plus venetoclax groups. We compared immune cell subsets in samples collected at 7 time points with age-matched healthy donors. CLL cells decreased within 3 cycles after venetoclax initiation; from cycle 16 onward, levels were similar to healthy donor levels (HDL; ≤0.8 cells per μL) in patients with Confirmed uMRD and slightly above HDL in patients without Confirmed uMRD. By 4 months after cycle 16, normal B cells had recovered to HDL in patients randomly assigned to placebo. Regardless of randomized treatment, abnormal counts of T cells, classical monocytes, and conventional dendritic cells recovered to HDL within 6 months (median change from baseline -49%, +101%, and +91%, respectively); plasmacytoid dendritic cells recovered by cycle 20 (+598%). Infections generally decreased over time regardless of randomized treatment and were numerically lowest in patients randomly assigned to placebo within 12 months after cycle 16. Sustained elimination of CLL cells and recovery of normal B cells were confirmed in samples from patients treated with fixed-duration ibrutinib plus venetoclax in the GLOW study (NCT03462719). These results demonstrate promising evidence of restoration of normal blood immune composition with ibrutinib plus venetoclax.

Published
2023

7. Hairy cell leukemia variant and WHO classification correspondence Re: 5th edition WHO classification haematolymphoid tumors: lymphoid neoplasms

Author

Grever, Michael, Andritsos, Leslie, Anghelina, Mirela, Arons, Evgeny, Banerji, Versha, Barrientos, Jacqueline, Bhat, Seema A., Blachly, James, Broccoli, Alessandro, Call, Timothy, Dearden, Claire, Dietrich, Sascha, Else, Monica, Epperla, Narendranath, Fagarasanu, Andrei, Falini, Brunangelo, Forconi, Francesco, Gozzetti, Alessandro, Hampel, Paul, Hermel, David J., Iyengar, Sunil, Johnston, James B., Juliusson, Gunnar, Kreitman, Robert J., Lauria, Francesco, Lozanski, Gerard, Oakes, Christopher C., Parikh, Sameer A., Park, Jae, Quest, Graeme, Rai, Kanti, Ravandi, Farhad, Robak, Tadeusz, Rogers, Kerry A., Saven, Alan, Seymour, John F., Tadmor, Tamar, Tallman, Martin S., Tam, Constantine S., Tiacci, Enrico, Troussard, Xavier, Wörmann, Bernhard, Zent, Clive S., Zenz, Thorsten, and Zinzani, Pier Luigi

Published
2024
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8. Outcomes in Patients with High-Risk Features after Fixed-Duration Ibrutinib plus Venetoclax: Phase II CAPTIVATE Study in First-Line Chronic Lymphocytic Leukemia.

Author

Allan, John, Flinn, Ian, Siddiqi, Tanya, Ghia, Paolo, Tam, Constantine, Barr, Paul, Elinder Camburn, Anna, Tedeschi, Alessandra, Badoux, Xavier, Jacobs, Ryan, Kuss, Bryone, Trentin, Livio, Zhou, Cathy, Szoke, Anita, Abbazio, Christopher, Wierda, William, and Kipps, Thomas

Subjects
Humans, Leukemia, Lymphocytic, Chronic, B-Cell, Piperidines, Bridged Bicyclo Compounds, Heterocyclic
Abstract

PURPOSE: The CAPTIVATE study investigated first-line ibrutinib plus venetoclax for chronic lymphocytic leukemia in 2 cohorts: minimal residual disease (MRD)-guided randomized discontinuation (MRD cohort) and Fixed Duration (FD cohort). We report outcomes of fixed-duration ibrutinib plus venetoclax in patients with high-risk genomic features [del(17p), TP53 mutation, and/or unmutated immunoglobulin heavy chain (IGHV)] in CAPTIVATE. PATIENTS AND METHODS: Patients received three cycles of ibrutinib 420 mg/day then 12 cycles of ibrutinib plus venetoclax (5-week ramp-up to 400 mg/day). FD cohort patients (n = 159) received no further treatment. Forty-three MRD cohort patients with confirmed undetectable MRD (uMRD) after 12 cycles of ibrutinib plus venetoclax received randomized placebo treatment. RESULTS: Of 195 patients with known status of genomic risk features at baseline, 129 (66%) had ≥1 high-risk feature. Overall response rates were >95% regardless of high-risk features. In patients with and without high-risk features, respectively, complete response (CR) rates were 61% and 53%; best uMRD rates: 88% and 70% (peripheral blood) and 72% and 61% (bone marrow); 36-month progression-free survival (PFS) rates: 88% and 92%. In subsets with del(17p)/TP53 mutation (n = 29) and unmutated IGHV without del(17p)/TP53 mutation (n = 100), respectively, CR rates were 52% and 64%; uMRD rates: 83% and 90% (peripheral blood) and 45% and 80% (bone marrow); 36-month PFS rates: 81% and 90%. Thirty-six-month overall survival (OS) rates were >95% regardless of high-risk features. CONCLUSIONS: Deep, durable responses and sustained PFS seen with fixed-duration ibrutinib plus venetoclax are maintained in patients with high-risk genomic features, with similar PFS and OS to those without high-risk features. See related commentary by Rogers, p. 2561.

Published
2023

9. Zanubrutinib Versus Ibrutinib in Relapsed/Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma: Interim Analysis of a Randomized Phase III Trial

Author

Hillmen, Peter, Eichhorst, Barbara, Brown, Jennifer R, Lamanna, Nicole, O'Brien, Susan M, Tam, Constantine S, Qiu, Lugui, Kazmierczak, Maciej, Zhou, Keshu, Šimkovič, Martin, Mayer, Jiří, Gillespie-Twardy, Amanda, Shadman, Mazyar, Ferrajoli, Alessandra, Ganly, Peter S, Weinkove, Robert, Grosicki, Sebastian, Mital, Andrzej, Robak, Tadeusz, Österborg, Anders, Yimer, Habte A, Salmi, Tommi, Ji, Meng, Yecies, Jessica, Idoine, Adam, Wu, Kenneth, Huang, Jane, and Jurczak, Wojciech

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Cardiovascular, Hematology, Clinical Research, Lymphoma, Cancer, Rare Diseases, Clinical Trials and Supportive Activities, Humans, Leukemia, Lymphocytic, Chronic, B-Cell, Atrial Fibrillation, Adenine, Lymphoma, B-Cell, Protein Kinase Inhibitors, Clinical Sciences, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

PurposeZanubrutinib is a potent, irreversible next-generation Bruton tyrosine kinase (BTK) inhibitor designed to maximize BTK occupancy and minimize off-target kinase inhibition. We hypothesized that complete/sustained BTK occupancy may improve efficacy outcomes and increased BTK specificity may minimize off-target inhibition-related toxicities.Patients and methodsALPINE (ClinicalTrials.gov identifier: NCT03734016) is a global, randomized, open-label phase III study of zanubrutinib versus ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia. The primary end point was investigator-assessed overall response rate (ORR). The preplanned interim analysis was scheduled approximately 12 months after the first 415 patients were enrolled.ResultsBetween November 1, 2018, and December 14, 2020, 652 patients were enrolled. We present the interim analysis of the first 415 enrolled patients randomly assigned to receive zanubrutinib (n = 207) or ibrutinib (n = 208). At 15 months of median follow-up, ORR (partial or complete response) was significantly higher with zanubrutinib (78.3%; 95% CI, 72.0 to 83.7) versus ibrutinib (62.5%; 95% CI, 55.5 to 69.1; two-sided P < .001). ORR was higher with zanubrutinib versus ibrutinib in subgroups with del(17p)/TP53 mutations (80.5% v 50.0%) and del(11q) (83.6% v 69.1%); 12-month progression-free survival in all patients was higher with zanubrutinib (94.9%) versus ibrutinib (84.0%; hazard ratio, 0.40; 95% CI, 0.23 to 0.69). Atrial fibrillation rate was significantly lower with zanubrutinib versus ibrutinib (2.5% v 10.1%; two-sided P = .001). Rates of cardiac events, major hemorrhages, and adverse events leading to treatment discontinuation/death were lower with zanubrutinib.ConclusionZanubrutinib had a significantly higher ORR, lower atrial fibrillation rate, and improved progression-free survival and overall cardiac safety profile versus ibrutinib. These data support improved efficacy/safety outcomes with selective BTK inhibition.

Published
2023

10. Tranexamic acid versus placebo to prevent bleeding in patients with haematological malignancies and severe thrombocytopenia (TREATT): a randomised, double-blind, parallel, phase 3 superiority trial

Author

Estcourt, Lise J, McQuilten, Zoe K, Bardy, Peter, Cole-Sinclair, Merrole, Collins, Graham P., Crispin, Philip J., Curnow, Elinor, Curnow, Jennifer, Degelia, Amber, Dyer, Claire, Friebe, Adam, Floro, Lajos, Grand, Effie, Hudson, Cara, Jones, Gail, Joseph, Joanne, Kallmeyer, Charlotte, Karakantza, Marina, Kerr, Paul, Last, Sara, Lobo-Clarke, Maria, Lumley, Matthew, McMullin, Mary F, Medd, Patrick G., Morton, Suzy M., Mumford, Andrew D., Mushkbar, Maria, Parsons, Joseph, Powter, Gillian, Sekhar, Mallika, Smith, Laura, Soutar, Richard, Stevenson, William S., Subramoniapillai, Elango, Szer, Jeff, Thomas, Helen, Waters, Neil A., Wei, Andrew H., Westerman, David A., Wexler, Sarah A., Wood, Erica M., Stanworth, Simon J., Abioye, Adrienne, Afghan, Rabia, Ai, Sylvia Ai, Akanni, Magbor, Alajangi, Rajesh, Alam, Usmaan, Al-Bubseeree, Bahaa, Alderson, Sophie, Alderson, Craig, Ali, Sayed, Ali, Kabir, Alighan, Rookmeen, Allam, Rebecca Allam, Allen, Tania, Al-Sakkaf, Wesam, Ames, Kate, Anderson, Jacqueline, Andrews, Colin, Angel, Ann-Marie, Anlya, Manuela Anlya, Ansari, Farah, Appleby, Rowan, Arnold, Claire, Asbjornsdottir, Hulda, Asfaw, Biruk, Atkins, Elissa, Atkinson, Leela, Aubrey, Clare, Ayesha, Noor, Babbola, Lola, Badcock, David, Badcock, Samuel, Baggio, Diva, Bailiff, Ben, Baines, Kizzy, Baker, Holly, Baker, Victoria, Ball, Lindsay, Ball, Martin, Balquin, Irwin, Banks, Emma, Banos, George, Barnett, Jaytee, Barrie, Claire, Barron, Claire, Barton, Rebecca, Bason, Nina, Batta, Bindu, Bautista, Dianne, Bayley, Angela, Bayly, Emma, Baynes, Fionnuala, Bazargan, Ali, Bazeley, Rachel, Beadle, Yvonne, Beardsmore, Claire, Beattie, Kate, Bedford, Caroline, Behal, Rachna, Behan, Daniel, Bejan, Lilihna, Bell, Sarah, Bell, Karen, Bell, Louise, Bell, Kaitlyn, Benjamin, Reuben, Bennett, Sam, Benson, Gary, Benson, Warwick, Bent, Cameron, Bergin, Krystal, Berry, Alex, Besenyei, Stephanie, Besley, Caroline, Betteridge, Scott, Beveridge, Leigh, Bhattacharyya, Abir, Billen, Annelies, Bilmon, Ian, Binns, Emma, Birt, Mark, Bishop, David, Blanco, Andrea, Bleby, Lisa, Blemnerhet, Richard, Blombery, Piers, Blyth, Emily, Blythe, Nicola, Boal, Lauren, Boden, Ali, Bokhari, Syed W.I., Bongetti, Elisa, Booth, Stephen, Borley, Jayne, Bowen, David, Bowers, Dawn, Boyd, Stephen, Bradley, Sarah, Bradman, Helen, Bretag, Peta, Brillante, Maria, Brockbank, Rachel, Brough, Yasmin, Brown, Ellen, Brown, Jo, Brown, Eleanor, Brown, Claire, Brown, Jenny, Brown, Susan, Browning, Joe, Brownsdon, Alex, Bruce, David, Brydon-Hill, Ruth, Buckwell, Andrea, Burgess, Dannielle, Burke, Glenda, Burley, Kate, Burney, Claire, Burns, David, Burrows, Samuel, burton, Kieran, Butler, Jason, Cambalova, Lenka, Camozzi, Maria C., Campbell, Philip, Campfield, Karen, Campion, Victoria, Cargo, Catherine, Carmona, Julia, Carney, Dennis, Casan, Joshua, Cashman, Helen, Catt, Lorraine, Cattell, Michael, Cavill, Megan, Chadbone, Rachel, Chaganti, Sridhar, Chai, Yee, Chai, Khai Li, Chang, Joshua, Chapman, Judith, Chapman, Oliver G., Chapter, Tamika, Charlton, Andrew, Chau, Celina, Chauhan, Saleena, Chavda, Nikesh, Chen, Frederick, Chen, Melody, Chen, Meng Xi, Chen, Melanie, Chen, Melissa, Cheok, Kathleen, Cheung, Mai, Chidgey, Luke, Chmielokliec, Karolina, Choi, Philip, Choi, Jae, Chok, Anne, Chopra, Ruchika, Christopherson, Louise, Chu, Vicky, Chua, Chong Chyn, Chudakou, Pavel, Chugh, Vidushi, Chung, Chi, Clark, Erin, Clarke, Peter, Clarke, Kathleen, Clay, Jennifer, Clayton, Laura, Clements, Mitch, Clemmens, Jonathan, Clifford, Ruth, Collett, Dave, Collins, Maia, Collyer, Emily, Connolly, Maureen, Cook, Mark, Coombs, Sarah, Coppell, Jason, Cornwell, Sophie, Corrigan, Claire, Coughlin, Elizabeth, Couling, Jennifer, Cousins, Tony, Cowan, Catriona, Cox, Christine, Cox, Catherine, Coyle, Luke, Craig, Emily, Creasey, Thomas, Croan, Laura, Croft, Jane, Crosbie, Nicola, Crowe, Josephine, Crowther, Helen, Crozier, Jane, Culleton, Naomi, Cullis, Jonathan, Cumming, Anita, Cummins, Michelle, Cunningham, Adam, Curley, Cameron, Curtis, Samantha, Cuthbert, Robert, Cuthill, Kirsty, Dahahayake, Dinusha A, Dang, Amy, Davies, Marc, Davies, Ceri, Dawson, Emily, Day, Tom, De Abrew, Kanchana, De Lavallade, Hugues, De Silva, Neelaskshi, Dean, Georgina, Deane, Christopher, Demosthenous, Lisa, Desai, Amisha, Desborough, Michael, Devanny, Ian, Dhanapal, Jay, Dhani, Sundip, Di Martino, Vicky, Dickens, Emmy, DiCorleto, Carmen, Dinnett, Louise, Dirisan, Divya, Dixon, Karen, Dixon, Kiri, Doal, Inderjit, Dobivh, J, Docanto, Maria, Doecke, Helve, Donaldson, David, Donaldson, Kylee, Donohoe, Carrie, Douglas, Ashley, Doung, Stephen, Downer, Susan, D'Rozario, James, Drummond, Malcolm, Drummond, Mark, Drummond, Samantha, Drysdale, Elizabeth, D'Souza, Ross, D'Souza, Eugene, Dunn, Alex, Dutton, David, Dyson, Martin, Ediriwicurena, Kushani, Edleston, Sharon, Edwards, Dawn, Edwards, Morgan, Edwards, Anita, Eise, Nicole, Ellis, Steven, Ellis, Hayley, Elmonley, Shareef, Enstone, Rosemarie, Eordogh, Agnes, Erb, Sharon, Evans, Shannon, Evans, Megan, Ewing, Joanne, Eyre, Toby, Facey, Adam, Fammy, Mina, Farman, Jon, Farnell, Rachel, Favero, Laura, Fay, Keith, Ferguson, Karen, Fernon, Laura, Filshie, Robin, Finnegan, Damian, Fisher, Lisa, Flanagan, Asia, Fleck, Emma, Fletcher, Simon, Flora, Harpreet, Flower, Catherine, Fodor, Ioana, Foley, Heather, Folland, Emma, Folorunso, Comfort, Forbes, Molly, Fordwor, Katrina, Foster, Polly, Fox, Vanessa, Fox, Thomas, Francis, Olesya, Fryearson, Louise, Fuery, Madonna, Fung, Jiin, Furtado, Michelle, Galloway-Browne, Leanne, Gamble, Louise, Gamgee, Jeanette, Ganapathy, Arundathi, Gardner, Hayley, Gardner, Clare, Gasmelsheed, Noha, Gately, Amy, Gaynor, Lynda, Gebreid, Alex, Geffens, Ruth, George, Rachel, Gertner, Aniko, Ghebeh, Manar, Ghirardini, Emanuela, Giddings, Melainie, Gillett, Sandra, Gillett, Karen, Giri, Pratyush, Glass, Chris, Glewis, Sarah, Gooding, Sarah, Gordon, Olivia, Gordon, Joanne, Gottlieb, David, Gowda, Koushik, Gower, Elysie, Gray, Nicola, Grayer, Jo, Greaves, Elaine, Greenaway, Sally Anne, Greenfield, Graeme, Greenwood, Matthew, Gregory, Gareth, Griffin, James, Griffith, Julia, Griffith, James, Griffiths, Lindsey, Grzegrzolka, Paulina, Gu, Yisu, Guest, Jo, Guinai, Rosanna, Gullapalli, Veena, Gunolr, A., Guo, Lina, H, Wayne, Hagua, Sophia, Haile, Senait, Hall, Richard, Hamdollah-Zadeh, Maryam, Hanif, Zahra, Hanlon, Kathleen, Hann, Nicholas, Hanna, Ramez, Hannah, Guy, Hapuarachchi, Sameera, Hardman, Jacinta, Hardy, Alison, Harris, Anthony, Harris, Kylie, Harrison, Beth, Harrison, Simon, Harrison, Lea-Anne, Harrop, Sean, Harvey, Caroline, Hatcliffe, Faye, Hawking, Jo, Hawkins, Matthew, Hayden, Janet, Hayman, Michelle, Haynes, Elizabeth, Heaney, Nicholas, Hebbard, Andrew, Hempton, Jenny, Hendunneti, Sasanka, Henry, Maeve, Heywood, Jonathan, Hildyard, Catherine, Hill, Lydia, Hilldrith, Annette, Hitev, Petar, Hiwase, Smita, Hiwase, Devendra, Hoare, Chris, Hodge, Renate, Holloway, Amy, Holt, Chloe, Holton, Kelly, Homer, Lauren, Horne, Gillian, Horvath, Noemi, Hotong, Linda, Houdyk, Kristen, Houseman, Katy, Hoxhallari, Ilda, Hsu, Hannah, Hsu, Nina, Huang, Gillian, Hudson, Kerryn, Hufton, Melanie, Hughes, Timothy, Hughes, Siobhan, Hurley, Kate, Huxley, Rosie, Ibitoye, Temitope, Ibrouf, Abubaken, Inam, Farha, Indran, Tishya, Ingham, Karen, Innes, Calum, Irvine, David, Jaafar, Sarah, Jain, Manish, Jameson, Laura, Janjua, Pardeep, Jarvis, Rebecca, Jatheendran, Abirami, Javed, Abbie, Jen, Sheila, Jobanpura, Shailesh, Jobson, Irene, John, Deborah, Johns, Sophie, Johnston, Amanda, Jones, Hollie, Jones, Francesca, Joniak, Karolina, Jovanovic, Michael, Jovic, Anita, Joyce, Lauren, Judd, Andrew, Kakarlamudi, Sudhakar, Kakaroubas, Nick, Kalita, Maggie, Kam, Shirly, Kan, Julie, Kandle, P, Kanellopoulos, Alex, Kao, Chien, Kaparou, Maria, Kartsios, Charamlampos, Katsioulas, Vicki, Kaye, Russell, Keen, Katie, Kelly, Richard, Kelly, Pauline, Kelly, Donna, Kelly, Melanie, Kennedy, Glen, Kennedy, Nola, Kenny, Angela, Kenworthy, Zoe, Kerridge, Ian, Kesavan, Murali, Khafizi, Angelika, Khakwani, Muhammad, Khalid, Amna, Khamly, Kate, Khan, Anjum, Khan, Dalia, Khan, Mojid, Khan, Lubna, Khoo, Mona, Khwaja, Asim, Kim, Grace, King, Andrew, King, Vicky, King, Donna, Kinsella, Francesca, Kipp, David, Kirandeep, Pachoo, Kirui, Laura C., Kishore, Bhuvan, Knectlhi, Christopher, Knot, Amy, Knot, Armit, Ko, Cathy, Kolaric, Caitlin, Koo, Ray, Kotadia, Mary, Kothari, Jaimal, Kottaridis, Panagiotis D., Kuiluinathan, Gajan, Kulasekararaj, Austin, Kwan, John, Kwok, Marwan, Kwok, Phillip, Kwok, Fiona, Laane, Kristiina, Lad, Deena, Laird, Jennifer, Lam, Ada, Lane, Mary, Lanenco, Monica, Lang, Susan, Langridge, Alex, Langton, Catherine, Lannon, Michelle, Latif, Annie, Latimer, Maya, Latter, Ruth, Lau, I-Jun, Lawless, Sarah, Lawless, Theresa, Leach, Mike, Leaney, Sarah, Leary, Heather, Leavy, James, LeBlanc, Abbey, Lee, Vivienne, Lee, Edwin, Lee, Jenny, Lee, Tamara, Leischkie, Marian, Leitinger, Emma, Leon, Christopher, Leonard, Jayne, Lewis, David, Lewis, Ian, Lewis, Tania, Lim, Daniel, Littlewood, Kelly, Liu, Dara, Loh, Joanna, Lokare, Anand, Lomas, Oliver, Lovell, Richard, Lowe, Theresa, Lowry, Lisa, Lubowiecki, Marcin, Lumb, Rebecca, Lynch, Gail, Macaulay, Amanda, MacDonald, Lyndsey, MacDonald-Burn, Jill, Macmillan, Margaret, Maddock, Karen, Mahaliyana, Tomas, Mahon, Cassandra, Maidment, Alison, Maier, Susie, Mairos, Michelle, Majid, Mahseeman, Mak, Ka L, Mak, Anne, Malendrayogau, Arunthrthy, Malham, Hana, Malyon, Felicity, Mandadapu, Vineela, Mandel, Laura, Mant, Sarah, Manton, Ruth, Maouche, Nadjoua, Maqbool, Muhammad G., Marchant, Gregory, Marinho, Mariana, Marks, David, Marner, Mike, Marr, Helen, Marshall, Gillian, Martin, Siobhan, Martin, Abigail, Marzolini, Maria, Mason, Kiara, Massie, Jonathan, Masson, Rebecca, Mathavan, Vidya, Mathew, Siju, Mathie, Judith, Mattocks, Lehenta, Maybury, Bernard, Mayer, Georgina, McAlister, Chyrelle, McAllister, Jo, McConnell, Stewart, McCracken, James, McCullagh, Liz, McCulloch, Rory, Mcdermott, Christopher, Mcdonald, Kerian, McGinniss, Laura, McGurk, Fiona, McIlwain, Jessica, McIver, Kirsten, Mckay, Pam, McKenna, Lorraine, Mclornan, Donal, McMahon, Coalon, McNeice, Linda, McNeill, Susan, McNickle, Molly, McQueen, Fiona, McRae, Simon, McTaggart, Bobby, Mehew, Jenny, Mehra, Varnn, Melly, Michelle, Menichelli, Tara, Micklethwatte, Ken, Mihailescue, Loredana, Mijovic, Aleksander, Millband, Hannah, Miller, Lucy, Millien, Samuel T., Milnthorpe, James, Minson, Adrian, Molnar, Eva, Monsour, Marc, Moody, Mary, Moon, Rebecca, Moore, Sally, Moore, Katy, Morgan, Kelly, Morralley, Rebecca, Morris, Denise, Morris, Kirk, Morrison, Nicole, Moss, Merinda, Mughal, Muhammad, Muir, Paul, Mukkath, David, Mulla, Aasiyu, Mulligan, Stephen, Mullings, Joanne, Mulqueen, Angela, Muluey, Caitlin, Murdoch, Sarah, Murrani, Sura, Murthy, Vidhya, Musngi, Jimmy, Mustafa, Nadreen, Mynes, Tracey, Nalpantidis, Anastasios, Nandurkar, Harshal, Nardone, Linda, Nasari, Latifa, Nash, Monica, Naylor, Georgina, Ngu, Loretta, Nguethina, Melissa, Nguyen, John, Nguyen, Joseph, Nichol, Wendy, Nicholls, Emma, Nicole, Catherine S., Nicolson, Phillip, Nielson, David, Nikolousis, Emmanouil, Nix, Georgina, Njoku, Rita, Norman, Jane, Norman, Amy, Norris, Phoebe, North, Daniel, Norwood, Megan, Notcheva, Gaynor, Novitzky-Basso, Igor, Nyaboko, Joseph, Nygren, Maria, Obu, Ingrid, O'Connell, Siobhan, O'Connor, Jody, O'Kelly, Deanna, O'Niell, Aideen, Ony, Jeremy, Oo, Kathy, Oo, April, Oppermann, Anne, Orr, Ruth, O'Sullivan, Mary, Page, Jennifer, Palfreyman, Emma, Paneesha, Shankaranarayana, Panicker, Shyam, Parbutt, Catherine, Parigi, Elesha, Paris, Gemma, Parker, Tracey, Parnell, Caroline, Parrish, Christopher, Parsons, Alex, Pasat, Mioara, Patel, Natasha, Patel, Vijay, Patel, Pooja, Patel, Chaya, Pati, Nalini, Patterson, Andrea, Paul, Lauren, Payet, Danielle, Payne, Elspeth, Peachey, Victoria, Pearson, Amanda, Peniket, Andy, Percy, Laura, Pereyra, Millicent, Pervaiz, Omer, Phalod, Gunjan D, Pham, Anh, Pho, Jason, Pickard, Keir, Pidcock, Michael, Piggin, Anna, Pishyar, Yalda, Pocock, Abigail, Pol, Ranjendres, Polzella, Paolo, Poolan, Sonia, Portingale, Vicki, Posnett, Claire, Potluri, Sandeep, Potter, Victoria, Pratt, Guy, Prodger, Catherine, Pueblo, Andres, Puliyayil, Anish, Puvanakumar, Pratheepan, Qadri, Abdul, Quach, Hang, Quinn, Michael, Rafferty, Mark, Rahman, Marzia, Raj, Kavita, Raj, Sonia, Rajendran, Ramina, Ramanan, Radha, Ramasamy, Karthik, Rampotas, Alexandros, Ranchhod, Natasha, Rashid, Sabia, Ratanjee, Sunita, Rathore, Gurpreet, Ratnasingam, Sumita, Rayat, Manjit, Rayner, Michael, Reddell-Denton, Rebecca, Redding, Nicola, Reddy, Udaya, Rehman, Atique, Rice, Carol, Riches, Iwona, Rider, Thomas, Riley, John, Rinaldi, Ciro, Roberts, Kayleigh, Roberts, Andrew, Robertson, Bryony, Robertson, Peter, Robinson, Dan, Robinson, Rebecca, Robjohns, Emma, Robledo, Laura, Rodrigues, Ana, Rofe, Chris, Roff, Bridie, Rogers, Rachel, Rolt, Jill, Rooney, Carmela, Rose, Kathy, Rose, Hannah, Ross, David, Rouf, Shahara, Rourke, Claire, Routledge, David, Ruggiero, Janet, Rule, Simon, Rumsey, Richard, Sagge, Cherry, Saldhana, Helen, Salisbury, Richard, Salisbury, Sarah, Salvaris, Ross, Sanders, Kay, Sangombe, Mirriam, Sanigorska, Anna, Santos, Kristine, Sarkis, Taylah, Sarma, Anita, Saunders, Natalie, Schmidt, Kara, Schmidtmann, Anja, Schumacher, Ann, Scorer, Tom Scorer, Scott, Asleigh, Seath, Ingrid, Sejman, Frances, Selim, Adrian, Shamim, Nadia, Shan, Jocelyn, Shanmuganathan, Naranie, Shanmugaranjan, Shaminie, Sharpe, Michelle, Sharpley, Faye, Shaw, Emma, Sheath, Cara, Sheehy, Oonagh, Shen, Vivian, Sherbide, Solomon, Sheridan, Mathew, Sheridan, Jane, Sheridon, Matthew, Shields, Tracy, Sim, Hau V, Sim, Shirlene, Sims, Matt, Singaraveloo, Lydia, Singh, Gurcharan, Singh, Jasmine, Sladesal, Shree, Sloan, Andrew, Slobodian, Peter, Smith, Sophie, Smith, Sarit, Smith, Claire, Smith, Alastair, Smith, Neil, Snowden, Katherine, Solis, Joel, Somios, Denise, Soo, Jade, Spanevello, Michelle, Spaulding, Madeleie, Spence, Laura, Spillane, Liz, Spiteri, Alisha, Sprigg, Naomi, Springett, Sally, Stafford, Lynn, Stainthorp, Katherine, Stark, Kate, Steeden, Louise, Stephen, Ella, Stephenson, Aisling, Stewart, Andrew, Stewart, Orla, Stobie, Emma, Stokes, Chelsea, Streater, Jacqui, Suddens, Charlie-Marie, Suntharalingam, Surenthini, Surana, Narinder, Sutherland, Robyn, Sutherland, Antony, Sutton, David, Sweeney, Connor, Sweet, Reilly, Szucs, Aniko P, Taheri, Leila E., Tailor, Hinesh, Tam, Constantine, Tambakis, George, Tamplin, Mary, Tan, Chee, Tan, Sui, Tan, Joanne, Tan, Zhi, Taran, Tatiana, Tarpey, Fiona, Taseka, Angela, Tasker, Suzy, Tatarczuch, Maciej, Tayabali, Sarrah, Taylor, Hannah, Taylor, Robert, Taylor, Melaine, Taylor-Moore, Ella, Teasdale, Lesley, Tebbet, Elizabeth, Tedjasepstra, Aditya, Tedjaseputra, Aditya, Tepkumkun, Oummy, Terpstra, Andrew, Thomas, Wayne, Thomas, Shanice, Thompson, Rachel, Thornton, Thomas, Thorp, Bronwyn, Thrift, Moi Yap, Thwaites, Phillipa, Timbres, Jasmine, Tindall, Lauren, Tiong, Ing Soo, Tippler, Nicole, Todd, Tony, Todd, Shirley, Toghill, Neil, Tomlinson, Eve, Tooth, Jacinta, Topp, M., Trail, Nicola, Tran, Nguyen, Tran, Elizabeth, Tran, Vi, Treder, Bona, Tribbeck, Michelle, Trochowski, Siobhan, Truslove, Maria, Tse, Tsun, Tseu, Bing, Tucker, David, Turner, Kelly, Turner, Dianne, Turner, Herleen, Turner, Gillian, Twohig, Julie, Tylee, Thomas, Uhe, Micheleine, Underhill, Lauren, V, Joanne, Van der Vliet, Georgina, Van Tonder, Tina, VanderWeyden, Carrie, Varghese, Jerry, Vaughan, Lachlan, Veale, David, Vickaryyous, Nicky, Vince, Kathryn, Von Welligh, Jacoba, Vora, Sona, Wadehra, Karan, Walker, Rebecca, Walker, Stephen, Wallace, Roslyn, Wallniosve, Stephanie, Wallwork, S., Walmsley, Zoe, Walters, Fiona, Wang, Joyce, Wang, Angela, Wang, Chen, Wanyika, Mercy, Warcel, Dana, Wardrobe, Katrina, Warnes, Kristian, Waterhouse, Christopher, Waterworth, Adam, Watson, Caroline, Watson, Edmund, Watts, Emily, Weaver, Emma, Weber, Nicholas, Webley, Kaytie, Welford, Anna, Wells, Matt, Westbury, Sarah, Westcott, Jackie, Western, Robyn, Weston, Julia, White, Jessica, White, Phillipa, Whitehead, Anna, Whitehouse, James, Wieringa, Samantha, Willan, John, Williams, Sandra, Williams, Bethany, Williamson, Stephanie, Willoughby, Brett, Wilmot, Gail, Wilmott, Rosalind, Wilson, Joanna, Wilson, Emma, Wilson, Suzy, Wilson, Heather, Wilson, Caroline, Wilson, Tanya, Wilton, Margaret, Wiltshire, Paula, Wincup, Joanne, Wolf, Julia, Wong, Henna, Wong, Cyndi, Wong, Daniel, Wong, Jonathan, Wong, Shi Qin, Wood, Sarah, Wood, Henry, Wooding, Jackie, Woolley, Kelly, Wright, Myles, Wynn-Williams, Roland, Yannakou, Costas, Yeoh, Zhi Han, Yeung, David, Young, Agnes, Yuen, Flora, Yuen, Agnes, Zaja, Oliver, Zhang, Xiao-Yin, and Zhang, Mei

Published
2025
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11. Venetoclax dose escalation rapidly activates a BAFF/BCL-2 survival axis in chronic lymphocytic leukemia

Author

Luo, Meng-Xiao, Tan, Tania, Trussart, Marie, Poch, Annika, Nguyen, Thi Minh Hanh, Speed, Terence P., Hicks, Damien G., Bandala-Sanchez, Esther, Peng, Hongke, Chappaz, Stéphane, Slade, Charlotte, Utzschneider, Daniel T., Koldej, Rachel M., Ritchie, David, Strasser, Andreas, Thijssen, Rachel, Ritchie, Matthew E., Tam, Constantine S., Lindeman, Geoffrey J., Huang, David C. S., Lew, Thomas E., Anderson, Mary Ann, Roberts, Andrew W., Teh, Charis E., and Gray, Daniel H. D.

Published
2024
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12. Sustained benefit of zanubrutinib vs ibrutinib in patients with R/R CLL/SLL: final comparative analysis of ALPINE

Author

Brown, Jennifer R., Eichhorst, Barbara, Lamanna, Nicole, O’Brien, Susan M., Tam, Constantine S., Qiu, Lugui, Jurczak, Wojciech, Zhou, Keshu, Šimkovič, Martin, Mayer, Jiří, Gillespie-Twardy, Amanda, Ferrajoli, Alessandra, Ganly, Peter S., Weinkove, Robert, Grosicki, Sebastian, Mital, Andrzej, Robak, Tadeusz, Osterborg, Anders, Yimer, Habte A., Wang, Megan, Salmi, Tommi, Wang, Liping, Li, Jessica, Wu, Kenneth, Cohen, Aileen, and Shadman, Mazyar

Published
2024
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13. Effective Tumor Debulking with Ibrutinib Before Initiation of Venetoclax: Results from the CAPTIVATE Minimal Residual Disease and Fixed-Duration Cohorts

Author

Barr, Paul M, Tedeschi, Alessandra, Wierda, William G, Allan, John N, Ghia, Paolo, Vallisa, Daniele, Jacobs, Ryan, O'Brien, Susan, Grigg, Andrew P, Walker, Patricia, Zhou, Cathy, Ninomoto, Joi, Krigsfeld, Gabriel, and Tam, Constantine S

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Cancer, Rare Diseases, Clinical Research, Hematology, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Adenine, Antineoplastic Combined Chemotherapy Protocols, Bridged Bicyclo Compounds, Heterocyclic, Creatinine, Cytoreduction Surgical Procedures, Humans, Leukemia, Lymphocytic, Chronic, B-Cell, Neoplasm, Residual, Piperidines, Sulfonamides, Tumor Lysis Syndrome, Oncology & Carcinogenesis, Clinical sciences, Oncology and carcinogenesis
Abstract

PurposeThe phase II CAPTIVATE study investigated first-line treatment with ibrutinib plus venetoclax for chronic lymphocytic leukemia in two cohorts: minimal residual disease (MRD)-guided randomized treatment discontinuation (MRD cohort) and fixed duration (FD cohort). We report tumor debulking and tumor lysis syndrome (TLS) risk category reduction with three cycles of single-agent ibrutinib lead-in before initiation of venetoclax using pooled data from the MRD and FD cohorts.Patients and methodsIn both cohorts, patients initially received three cycles of ibrutinib 420 mg/day then 12 cycles of ibrutinib plus venetoclax (5-week ramp-up to 400 mg/day).ResultsIn the total population (N = 323), the following decreases from baseline to after ibrutinib lead-in were observed: percentage of patients with a lymph node diameter ≥5 cm decreased from 31% to 4%, with absolute lymphocyte count ≥25 × 109/L from 76% to 65%, with high tumor burden category for TLS risk from 23% to 2%, and with an indication for hospitalization (high TLS risk, or medium TLS risk and creatinine clearance

Published
2022

14. Pirtobrutinib, a highly selective, non-covalent (reversible) BTK inhibitor in patients with B-cell malignancies: analysis of the Richter transformation subgroup from the multicentre, open-label, phase 1/2 BRUIN study

Author

Wierda, William G, Shah, Nirav N, Cheah, Chan Y, Lewis, David, Hoffmann, Marc S, Coombs, Catherine C, Lamanna, Nicole, Ma, Shuo, Jagadeesh, Deepa, Munir, Talha, Wang, Yucai, Eyre, Toby A, Rhodes, Joanna M, McKinney, Matthew, Lech-Maranda, Ewa, Tam, Constantine S, Jurczak, Wojciech, Izutsu, Koji, Alencar, Alvaro J, Patel, Manish R, Seymour, John F, Woyach, Jennifer A, Thompson, Philip A, Abada, Paolo B, Ho, Caleb, McNeely, Samuel C, Marella, Narasimha, Nguyen, Bastien, Wang, Chunxiao, Ruppert, Amy S, Nair, Binoj, Liu, Hui, Tsai, Donald E, Roeker, Lindsey E, and Ghia, Paolo

Published
2024
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17. Recognizing Unmet Need in the Era of Targeted Therapy for CLL/SLL: “What's Past Is Prologue” (Shakespeare)CLL/SLL Unmet Need

Author

Mato, Anthony R, Davids, Matthew S, Sharman, Jeff, Roeker, Lindsey E, Kay, Neil, Kater, Arnon P, Rogers, Kerry, Thompson, Meghan C, Rhodes, Joanna, Goy, Andre, Skarbnik, Alan, Schuster, Stephen J, Tam, Constantine S, Eyre, Toby A, O'Brien, Susan, Nabhan, Chadi, Lamanna, Nicole, Sun, Clare, Shadman, Mazyar, Pagel, John M, Ujjani, Chaitra, Brander, Danielle, Coombs, Catherine C, Jain, Nitin, Cheah, Chan Y, Brown, Jennifer R, Seymour, John F, and Woyach, Jennifer A

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Rare Diseases, Clinical Research, Hematology, Lymphoma, Cancer, Humans, Immunotherapy, Leukemia, Lymphocytic, Chronic, B-Cell, Phosphatidylinositol 3-Kinases, Protein Kinase Inhibitors, Oncology & Carcinogenesis, Clinical sciences, Oncology and carcinogenesis
Abstract

The management of chronic lymphocytic leukemia (CLL) has undergone unprecedented changes over the last decade. Modern targeted therapies are incorporated into clinical practice. Unfortunately, patients have begun to develop resistance or intolerance to multiple classes. Symptomatic patients previously treated with a BTK inhibitor (BTKi) and venetoclax represent a new and rapidly growing unmet need in CLL. Here, we define unmet needs in a modern treatment context. We also critically review the literature for PI3K inhibitors and chemoimmunotherapy and lack of data to support their utility following BTKis and venetoclax. Finally, we suggest opportunities to ensure the continued innovation for patients with CLL.

Published
2022

18. Biomarker analysis of the ASPEN study comparing zanubrutinib with ibrutinib for patients with Waldenström macroglobulinemia

Author

Tam, Constantine S., Opat, Stephen, D'Sa, Shirley, Jurczak, Wojciech, Lee, Hui-Peng, Cull, Gavin, Owen, Roger G., Marlton, Paula, Wahlin, Björn E., García-Sanz, Ramón, McCarthy, Helen, Mulligan, Stephen, Tedeschi, Alessandra, Castillo, Jorge J., Czyż, Jarosław, Fernández De Larrea, Carlos, Belada, David, Libby, Edward, Matous, Jeffrey, Motta, Marina, Siddiqi, Tanya, Tani, Monica, Trněný, Marek, Minnema, Monique C., Buske, Christian, Leblond, Véronique, Treon, Steven P., Trotman, Judith, Wu, Binghao, Yu, Yiling, Shen, Zhirong, Chan, Wai Y., Schneider, Jingjing, Allewelt, Heather, Cohen, Aileen, and Dimopoulos, Meletios A.

Published
2024
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19. CAR T cells and time-limited ibrutinib as treatment for relapsed/refractory mantle cell lymphoma: the phase 2 TARMAC study

Author

Minson, Adrian, Hamad, Nada, Cheah, Chan Y., Tam, Constantine, Blombery, Piers, Westerman, David, Ritchie, David, Morgan, Huw, Holzwart, Nicholas, Lade, Stephen, Anderson, Mary Ann, Khot, Amit, Seymour, John F., Robertson, Molly, Caldwell, Imogen, Ryland, Georgina, Saghebi, Javad, Sabahi, Zahra, Xie, Jing, Koldej, Rachel, and Dickinson, Michael

Published
2024
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22. Peripheral neuropathy in the phase 3 ASPEN study of Bruton tyrosine kinase inhibitors for Waldenström macroglobulinemia

Author

Heyman, Benjamin M., Opat, Stephen S., Wahlin, Björn E., Dimopoulos, Meletios-Athanasios A., Castillo, Jorge J., Tedeschi, Alessandra, Tam, Constantine S., Buske, Christian, Owen, Roger G., LeBlond, Véronique, Trotman, Judith, Barnes, Gisoo, Chan, Wai Y., Schneider, Jingjing, Allewelt, Heather, Cohen, Aileen, and Matous, Jeffrey V.

Published
2024
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24. Other malignancies in the history of CLL: an international multicenter study conducted by ERIC, the European Research Initiative on CLL, in HARMONY

Author

Chatzikonstantinou, Thomas, Scarfò, Lydia, Karakatsoulis, Georgios, Minga, Eva, Chamou, Dimitra, Iacoboni, Gloria, Kotaskova, Jana, Demosthenous, Christos, Smolej, Lukas, Mulligan, Stephen, Alcoceba, Miguel, Al-Shemari, Salem, Aurran-Schleinitz, Thérèse, Bacchiarri, Francesca, Bellido, Mar, Bijou, Fontanet, Calleja, Anne, Medina, Angeles, Khan, Mehreen Ali, Cassin, Ramona, Chatzileontiadou, Sofia, Collado, Rosa, Christian, Amy, Davis, Zadie, Dimou, Maria, Donaldson, David, Santos, Gimena Dos, Dreta, Barbara, Efstathopoulou, Maria, El-Ashwah, Shaimaa, Enrico, Alicia, Fresa, Alberto, Galimberti, Sara, Galitzia, Andrea, García-Serra, Rocío, Gimeno, Eva, González-Gascón-y-Marín, Isabel, Gozzetti, Alessandro, Guarente, Valerio, Guieze, Romain, Gogia, Ajay, Gupta, Ritu, Harrop, Sean, Hatzimichael, Eleftheria, Herishanu, Yair, Hernández-Rivas, José-Ángel, Inchiappa, Luca, Jaksic, Ozren, Janssen, Susanne, Kalicińska, Elżbieta, Laribi, Kamel, Karakus, Volkan, Kater, Arnon P., Kho, Bonnie, Kislova, Maria, Konstantinou, Eliana, Koren-Michowitz, Maya, Kotsianidis, Ioannis, Kreitman, Robert J., Labrador, Jorge, Lad, Deepesh, Levin, Mark-David, Levy, Ilana, Longval, Thomas, Lopez-Garcia, Alberto, Marquet, Juan, Martin-Rodríguez, Lucia, Maynadié, Marc, Maslejova, Stanislava, Mayor-Bastida, Carlota, Mihaljevic, Biljana, Milosevic, Ivana, Miras, Fatima, Moia, Riccardo, Morawska, Marta, Murru, Roberta, Nath, Uttam Kumar, Navarro-Bailón, Almudena, Oliveira, Ana C., Olivieri, Jacopo, Oscier, David, Panovska-Stavridis, Irina, Papaioannou, Maria, Papajík, Tomas, Kubova, Zuzana, Phumphukhieo, Punyarat, Pierie, Cheyenne, Puiggros, Anna, Rani, Lata, Reda, Gianluigi, Rigolin, Gian Matteo, Ruchlemer, Rosa, Daniel de Deus Santos, Marcos, Schipani, Mattia, Schiwitza, Annett, Shen, Yandong, Simkovic, Martin, Smirnova, Svetlana, Abdelrahman Soliman, Dina Sameh, Spacek, Martin, Tadmor, Tamar, Tomic, Kristina, Tse, Eric, Vassilakopoulos, Theodoros, Visentin, Andrea, Vitale, Candida, von Tresckow, Julia, Vrachiolias, George, Vukovic, Vojin, Walewska, Renata, Wasik-Szczepanek, Ewa, Xu, Zhenshu, Yagci, Munci, Yañez, Lucrecia, Yassin, Mohamed, Zuchnicka, Jana, Angelopoulou, Maria, Antic, Darko, Biderman, Bella, Catherwood, Mark, Claus, Rainer, Coscia, Marta, Cuneo, Antonio, Demirkan, Fatih, Espinet, Blanca, Gaidano, Gianluca, Kalashnikova, Olga B., Laurenti, Luca, Nikitin, Eugene, Pangalis, Gerassimos A., Panagiotidis, Panagiotis, Popov, Viola Maria, Pospisilova, Sarka, Sportoletti, Paolo, Stavroyianni, Niki, Tam, Constantine, Trentin, Livio, Chatzidimitriou, Anastasia, Bosch, Francesc, Doubek, Michael, Ghia, Paolo, and Stamatopoulos, Kostas

Published
2023
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26. ZNF683 marks a CD8+ T cell population associated with anti-tumor immunity following anti-PD-1 therapy for Richter syndrome

Author

Parry, Erin M., Lemvigh, Camilla K., Deng, Stephanie, Dangle, Nathan, Ruthen, Neil, Knisbacher, Binyamin A., Broséus, Julien, Hergalant, Sébastien, Guièze, Romain, Li, Shuqiang, Zhang, Wandi, Johnson, Connor, Long, Jaclyn M., Yin, Shanye, Werner, Lillian, Anandappa, Annabelle, Purroy, Noelia, Gohil, Satyen, Oliveira, Giacomo, Bachireddy, Pavan, Shukla, Sachet A., Huang, Teddy, Khoury, Joseph D., Thakral, Beenu, Dickinson, Michael, Tam, Constantine, Livak, Kenneth J., Getz, Gad, Neuberg, Donna, Feugier, Pierre, Kharchenko, Peter, Wierda, William, Olsen, Lars Rønn, Jain, Nitin, and Wu, Catherine J.

Published
2023
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28. BTK and PLCG2 remain unmutated in one-third of patients with CLL relapsing on ibrutinib

Author

Bonfiglio, Silvia, Sutton, Lesley-Ann, Ljungström, Viktor, Capasso, Antonella, Pandzic, Tatjana, Weström, Simone, Foroughi-Asl, Hassan, Skaftason, Aron, Gellerbring, Anna, Lyander, Anna, Gandini, Francesca, Gaidano, Gianluca, Trentin, Livio, Bonello, Lisa, Reda, Gianluigi, Bödör, Csaba, Stavroyianni, Niki, Tam, Constantine S., Marasca, Roberto, Forconi, Francesco, Panayiotidis, Panayiotis, Ringshausen, Ingo, Jaksic, Ozren, Frustaci, Anna Maria, Iyengar, Sunil, Coscia, Marta, Mulligan, Stephen P., Ysebaert, Loïc, Strugov, Vladimir, Pavlovsky, Carolina, Walewska, Renata, Österborg, Anders, Cortese, Diego, Ranghetti, Pamela, Baliakas, Panagiotis, Stamatopoulos, Kostas, Scarfò, Lydia, Rosenquist, Richard, and Ghia, Paolo

Published
2023
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30. Report of consensus panel 1 from the 11th International Workshop on Waldenstrom's Macroglobulinemia on management of symptomatic, treatment-naïve patients

Author

Buske, Christian, Castillo, Jorge J., Abeykoon, Jithma Prasad, Advani, Ranjana, Arulogun, Suzanne O., Branagan, Andrew R., Cao, Xinxin, D'Sa, Shirley, Hou, Jian, Kapoor, Prashant, Kastritis, Efstathios, Kersten, Marie J., LeBlond, Veronique, Leiba, Merav, Matous, Jeffrey V., Paludo, Jonas, Qiu, Lugui, Tam, Constantine S., Tedeschi, Alessandra, Thomas, Sheeba K., Tohidi-Esfahani, Ibrahim, Varettoni, Marzia, Vos, Josephine M., Garcia-Sanz, Ramon, San-Miguel, Jesus, Dimopoulos, Meletios A., Treon, Steven P., and Trotman, Judith

Published
2023
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32. Zanubrutinib Monotherapy for Naïve and Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Pooled Analysis of Three Studies

Author

Xu, Wei, Yang, Shenmiao, Tam, Constantine S., Seymour, John F., Zhou, Keshu, Opat, Stephen, Qiu, Lugui, Sun, Mingyuan, Wang, Tingyu, Trotman, Judith, Pan, Ling, Gao, Sujun, Zhou, Jianfeng, Zhou, Daobin, Zhu, Jun, Song, Yuqin, Hu, Jianda, Feng, Ru, Huang, Haiwen, Su, Dan, Shi, Miao, and Li, Jianyong

Published
2022
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33. Single-cell multiomics reveal the scale of multilayered adaptations enabling CLL relapse during venetoclax therapy

Author

Thijssen, Rachel, Tian, Luyi, Anderson, Mary Ann, Flensburg, Christoffer, Jarratt, Andrew, Garnham, Alexandra L., Jabbari, Jafar S., Peng, Hongke, Lew, Thomas E., Teh, Charis E., Gouil, Quentin, Georgiou, Angela, Tan, Tania, Djajawi, Tirta M., Tam, Constantine S., Seymour, John F., Blombery, Piers, Gray, Daniel H.D., Majewski, Ian J., Ritchie, Matthew E., Roberts, Andrew W., and Huang, David C.S.

Published
2022
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36. Zanubrutinib versus bendamustine and rituximab in untreated chronic lymphocytic leukaemia and small lymphocytic lymphoma (SEQUOIA): a randomised, controlled, phase 3 trial

Author

Tam, Constantine S, Brown, Jennifer R, Kahl, Brad S, Ghia, Paolo, Giannopoulos, Krzysztof, Jurczak, Wojciech, Šimkovič, Martin, Shadman, Mazyar, Österborg, Anders, Laurenti, Luca, Walker, Patricia, Opat, Stephen, Chan, Henry, Ciepluch, Hanna, Greil, Richard, Tani, Monica, Trněný, Marek, Brander, Danielle M, Flinn, Ian W, Grosicki, Sebastian, Verner, Emma, Tedeschi, Alessandra, Li, Jianyong, Tian, Tian, Zhou, Lei, Marimpietri, Carol, Paik, Jason C, Cohen, Aileen, Huang, Jane, Robak, Tadeusz, and Hillmen, Peter

Published
2022
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38. Fixed-duration ibrutinib plus venetoclax for first-line treatment of CLL: primary analysis of the CAPTIVATE FD cohort

Author

Tam, Constantine S., Allan, John N., Siddiqi, Tanya, Kipps, Thomas J., Jacobs, Ryan, Opat, Stephen, Barr, Paul M., Tedeschi, Alessandra, Trentin, Livio, Bannerji, Rajat, Jackson, Sharon, Kuss, Bryone J., Moreno, Carol, Szafer-Glusman, Edith, Russell, Kristin, Zhou, Cathy, Ninomoto, Joi, Dean, James P., Wierda, William G., and Ghia, Paolo

Published
2022
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39. Prognostic factors in chronic lymphocytic leukaemia – the old, the new and the future.

Author

McKeague, Sean and Tam, Constantine

Subjects
*CHRONIC lymphocytic leukemia, *CHIMERIC antigen receptors, *CHRONIC leukemia, *LYMPHOCYTIC leukemia, *PROGNOSIS
Abstract

AbstractPrognostic assessment in chronic lymphocytic leukemia (CLL) is essential for delivery of timely, personalized therapy. TP53 status, karyotype, IGHV mutational status, minimal residual disease (MRD), gene mutations and markers of cell proliferation were important prognostic tools in the era of chemo-immunotherapy (CIT). With BCL2 inhibitors (BCL2i), outcome is still impacted by IGHV status, TP53 status, complex karyotype, and achievement of undetectable MRD. On the other hand, BTK inhibitors (BTKi) are agnostic to IGHV status, rarely cause MRD negative remissions and are less clearly impacted by TP53 status. Although based on less mature data, outcomes with BCL2i/BTKi combinations are likely influenced by TP53 and IGHV status. Responses to non-covalent BTKI (ncBTKI) are impacted by the mechanism of resistance to previous covalent BTKi. Finally, responses to chimeric antigen receptor T cell therapy (CAR-T) appear independent of TP53 status, but dependent on overall T- cell fitness. [ABSTRACT FROM AUTHOR]

Published
2025
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40. Real-world treatment patterns and outcomes for patients with CLL using the Australian pharmaceutical benefits scheme (PBS) dataset.

Author

Tam, Constantine, Zhao, Fei-Li, Azam, Safee, Li, Shu Chuen, and Tang, Boxiong

Subjects
*BRUTON tyrosine kinase, *CHRONIC lymphocytic leukemia, *PROTEIN-tyrosine kinase inhibitors, *CD20 antigen, *VENETOCLAX
Abstract

This real-world retrospective cohort study using Australian Pharmaceutical Benefits Scheme (PBS) 10% investigated changes in chronic lymphocytic leukemia (CLL) treatment by line of therapy, time-to-next-treatment, treatment duration, and overall survival (OS). Overall, 803 patients received their first PBS-reimbursed CLL medication between 1 January 2011 to 31 July 2021 (median age: 70 years; 64.6% male), 289 post-1 August 2020. In 2011, most first-line (1 L) prescribing was fludarabine, cyclophosphamide, and rituximab (FCR). By 2021, common 1L were chlorambucil ± CD20 (26.1%), Bruton Tyrosine Kinase inhibitor (BTKi) (26.1%), and CD20 monotherapy (23.9%). In 2011, relapsed/refractory (R/R) CLL treatment was CD20 monotherapy or FCR. By 2021, BTKi (57.7%) and venetoclax ± CD20 (26.1%) were most common. Compared to FCR, 1 L treatment duration (Hazard Ratio) was shorter for CD20 monotherapy (1.7) or chlorambucil ± CD20 (2.5). In R/R CLL, median duration was 24 (ibrutinib) and 19 months (venetoclax). Median OS was 127 months. CLLtreatment pattern shave greatly changed in Australia since the introduction of novel therapies. [ABSTRACT FROM AUTHOR]

Published
2024
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42. Clonal hematopoiesis, myeloid disorders and BAX-mutated myelopoiesis in patients receiving venetoclax for CLL

Author

Blombery, Piers, Lew, Thomas E., Dengler, Michael A., Thompson, Ella R., Lin, Victor S., Chen, Xiangting, Nguyen, Tamia, Panigrahi, Ashish, Handunnetti, Sasanka M., Carney, Dennis A., Westerman, David A., Tam, Constantine S., Adams, Jerry M., Wei, Andrew H., Huang, David C.S., Seymour, John F., Roberts, Andrew W., and Anderson, Mary Ann

Published
2022
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43. Pooled safety analysis of zanubrutinib monotherapy in patients with B-cell malignancies

Author

Tam, Constantine S., Dimopoulos, Meletios, Garcia-Sanz, Ramon, Trotman, Judith, Opat, Stephen, Roberts, Andrew W., Owen, Roger, Song, Yuqin, Xu, Wei, Zhu, Jun, Li, Jianyong, Qiu, Lugui, D'Sa, Shirley, Jurczak, Wojciech, Cull, Gavin, Marlton, Paula, Gottlieb, David, Munoz, Javier, Phillips, Tycel, Du, Chenmu, Ji, Meng, Zhou, Lei, Guo, Haiyi, Zhu, Hongjie, Chan, Wai Y., Cohen, Aileen, Novotny, William, Huang, Jane, and Tedeschi, Alessandra

Published
2022
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45. Consensus opinion from an international group of experts on measurable residual disease in hairy cell leukemia

Author

Ravandi, Farhad, Kreitman, Robert J., Tiacci, Enrico, Andritsos, Leslie, Banerji, Versha, Barrientos, Jacqueline C., Bhat, Seema A., Blachly, James S., Broccoli, Alessandro, Call, Timothy, Chihara, Dai, Dearden, Claire, Demeter, Judit, Dietrich, Sasha, Else, Monica, Epperla, Narendranath, Falini, Brunangelo, Forconi, Francesco, Gladstone, Douglas E., Gozzetti, Alessandro, Iyengar, Sunil, Johnston, James B., Jorgensen, Jeffrey, Juliusson, Gunnar, Lauria, Francesco, Lozanski, Gerard, Parikh, Sameer A., Park, Jae H., Polliack, Aaron, Quest, Graeme, Robak, Tadeusz, Rogers, Kerry A., Saven, Alan, Seymour, John F., Tadmor, Tamar, Tallman, Martin S., Tam, Constantine S., Thompson, Philip A., Troussard, Xavier, Zent, Clive S., Zenz, Thorsten, Zinzani, Pier Luigi, Wörmann, Bernhard, Rai, Kanti, and Grever, Michael

Published
2022
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46. Comparative efficacy of Bruton tyrosine kinase inhibitors in the treatment of relapsed/refractory chronic lymphocytic leukemia: A network meta-analysis (NMA).

Author

Shadman, Mazyar, primary, Brown, Jennifer R., additional, Mohseninejad, Leyla, additional, Yang, Keri, additional, Burnett, Heather, additional, Neupane, Binod, additional, Williams, Rhys, additional, Lamanna, Nicole, additional, O'Brien, Susan M., additional, Tedeschi, Alessandra, additional, and Tam, Constantine S., additional

Published
2024
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47. Health-related quality of life in patients with Waldenström macroglobulinemia: results from the ASPEN trial.

Author

Tedeschi, Alessandra, Tam, Constantine S, Owen, Roger G, Buske, Christian, Leblond, Véronique, Dimopoulos, Meletios, Garcia-Sanz, Ramón, Castillo, Jorge J, Trotman, Judith, Treon, Steven P, Yang, Keri, Tang, Boxiong, Allewelt, Heather, Patel, Sheel, Chan, Wai Y, Cohen, Aileen, Chen, Shengnan, and Barnes, Gisoo

Abstract

Aim ASPEN is a randomized, open-label, Phase III study comparing zanubrutinib and ibrutinib in patients with Waldenström macroglobulinemia (WM). Materials & methods: Patient-reported outcomes were exploratory end points assessed using the EORTC QLQ-C30 and EQ-5D-5L VAS scores. Results: Overall, 201 patients (102 zanubrutinib; 99 ibrutinib) were enrolled. Clinically meaningful differences were observed in diarrhea and nausea/vomiting in both the intent-to-treat population and in patients attaining very good partial response (VGPR) in earlier cycles of treatment, as well as in long-term physical functioning and fatigue in patients achieving VGPR. Conclusion: Treatment with zanubrutinib was associated with greater improvements in health-related quality of life compared with ibrutinib in patients with WM and MYD88 mutations. Clinical Trial Registration:NCT03053440 (ClinicalTrials.gov) Plain Language Summary Patient quality of life is important What is this article about? This article talks about a study called the ASPEN trial, which compares two medicines used for treating a rare blood cancer that doctors call Waldenström macroglobulinemia. The medicines are called zanubrutinib (ZAN) and ibrutinib (IBR). They work in the same way, by blocking a protein called Bruton tyrosine kinase. When patients take medicines for an illness, it is important to learn about their physical, social, emotional and mental well-being (quality of life). In this study, we asked patients to fill out questionnaires about their well-being before starting the study treatment for their blood cancer, and again a few times while taking the medication, to see if there were any changes. What were the results of the study? There were two groups of patients. One group took ZAN and the other took IBR. The patients could not choose which medicine they were going to take. Results from both groups of patients were compared. Patients taking ZAN did not feel worse or better about their diarrhea and sickness, but those taking IBR said these symptoms had become worse. Both medicines improved how patients were feeling. However, improvement in tiredness and physical ability was larger in patients taking ZAN than those on IBR, especially for the patients whose cancer was getting better. What do the results mean? For patients with a rare blood cancer in this study, those taking ZAN had a better quality of life than those taking IBR. Tweetable Abstract In a head-to-head comparison in the Phase III ASPEN study, patients with Waldenström macroglobulinemia treated with zanubrutinib had better quality of life than patients treated with ibrutinib. Article highlights Waldenström macroglobulinemia (WM) is a rare B-cell lymphoma marked by an excess of monoclonal immunoglobulin-M. Patients with WM experience symptoms including fatigue, muscle weakness, neuropathy and anemia, significantly affecting their health-related quality of life (HRQoL). Bruton tyrosine kinase (BTK) inhibitors, particularly ibrutinib, have shown efficacy in treating WM; however, they are associated with adverse events that can lead to early treatment discontinuation, negatively affecting HRQoL. Zanubrutinib, a next-generation BTK inhibitor, was designed with improved selectivity for BTK to minimize off-target effects and toxicities and thereby potentially improve HRQoL. Materials & methods ASPEN is a randomized, open-label, Phase III study comparing zanubrutinib and ibrutinib in patients with relapsed/refractory or treatment-naive WM. In this study, HRQoL was measured with two validated patient-reported instruments: the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire – Core 30 and the EQ-5D-5L. Results Clinically meaningful improvements in diarrhea and nausea/vomiting symptoms were observed in patients receiving zanubrutinib compared with ibrutinib. Patients with a very good partial response to zanubrutinib had significantly increased HRQoL, particularly in physical functioning and fatigue symptoms. Both treatment arms had consistently improved EQ-5D-5L scores through Cycle 13. Discussion This is the first head-to-head study comparing HRQoL in patients with WM treated with different BTK inhibitors. The results reported here are consistent with the primary results of the ASPEN study reported by Tam et al. [10]. Conclusions In addition to the better efficacy observed with zanubrutinib vs. ibrutinib, zanubrutinib provides a higher quality of life to patients with WM. [ABSTRACT FROM AUTHOR]

Published
2024
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49. Venetoclax-rituximab is active in patients with BTKi-exposed CLL, but durable treatment-free remissions are uncommon

Author

Lew, Thomas E., primary, Bennett, Rory, additional, Lin, Victor S., additional, Whitechurch, Ashley, additional, Handunnetti, Sasanka M., additional, Marlton, Paula, additional, Shen, Yandong, additional, Mulligan, Stephen P., additional, Casan, Joshua, additional, Blombery, Piers, additional, Tam, Constantine S., additional, Roberts, Andrew W., additional, Seymour, John F., additional, Thompson, Philip A., additional, and Anderson, Mary A., additional

Published
2024
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50. Outcomes of Allogeneic Haematopoietic Transplant for Chronic Lymphocytic Leukaemia in the Modern Era

Author

Hamad, Nada, primary, Barge, Luani, additional, Tran, Steven, additional, Kennedy, Glen, additional, Ritchie, David, additional, Gottlieb, David, additional, Milliken, Samuel, additional, Spencer, Andrew, additional, Purtill, Duncan, additional, Perera, Travis, additional, Doocey, Richard, additional, Larsen, Stephen, additional, Butler, Andrew, additional, Bardy, Peter, additional, Greenwood, Matthew, additional, Durrant, Simon, additional, Curley, Cameron, additional, Stewart, Caroline, additional, Tam, Constantine, additional, Balendran, Shalini, additional, Ciaccio, Pietro Di, additional, Patil, Sushrut, additional, and Han, Min-Hi, additional

Published
2024
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