TY - JOUR
T1 - Predictive factors and outcomes for ibrutinib in relapsed/refractory marginal zone lymphoma
T2 - a multicenter cohort study
AU - Epperla, Narendranath
AU - Zhao, Qiuhong
AU - Chowdhury, Sayan Mullick
AU - Shea, Lauren
AU - Moyo, Tamara K.
AU - Reddy, Nishitha
AU - Sheets, Julia
AU - Weiner, David M.
AU - Geethakumari, Praveen Ramakrishnan
AU - Kandarpa, Malathi
AU - Bruno, Ximena Jordan
AU - Thomas, Colin
AU - Churnetski, Michael C.
AU - Hsu, Andrew
AU - Zurbriggen, Luke
AU - Tan, Cherie
AU - Lindsey, Kathryn
AU - Maakaron, Joseph
AU - Caimi, Paolo F.
AU - Torka, Pallawi
AU - Bello, Celeste
AU - Ayyappan, Sabarish
AU - Karmali, Reem
AU - Kim, Seo Hyun
AU - Kress, Anna
AU - Kothari, Shalin
AU - Sawalha, Yazeed
AU - Christian, Beth
AU - David, Kevin A.
AU - Greenwell, Irl Brian
AU - Janakiram, Murali
AU - Kenkre, Vaishalee P.
AU - Olszewski, Adam J.
AU - Cohen, Jonathon B.
AU - Palmisiano, Neil
AU - Umyarova, Elvira
AU - Wilcox, Ryan A.
AU - Awan, Farrukh T.
AU - Alderuccio, Juan Pablo
AU - Barta, Stefan K.
AU - Grover, Natalie S.
AU - Ghosh, Nilanjan
AU - Bartlett, Nancy L.
AU - Herrera, Alex F.
AU - Shouse, Geoffrey
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - Ibrutinib is effective in the treatment of relapsed/refractory (R/R) marginal zone lymphoma (MZL) with an overall response rate (ORR) of 48%. However, factors associated with response (or lack thereof) to ibrutinib in R/R MZL in clinical practice are largely unknown. To answer this question, we performed a multicenter (25 US centers) cohort study and divided the study population into three groups: “ibrutinib responders”—patients who achieved complete or partial response (CR/PR) to ibrutinib; “stable disease (SD)”; and “primary progressors (PP)”—patients with progression of disease as their best response to ibrutinib. One hundred and nineteen patients met the eligibility criteria with 58%/17% ORR/CR, 29% with SD, and 13% with PP. The median PFS and OS were 29 and 71.4 months, respectively, with no difference in PFS or OS based on the ibrutinib line of therapy or type of therapy before ibrutinib. Patients with complex cytogenetics had an inferior PFS (HR = 3.08, 95% CI 1.23–7.67, p = 0.02), while those with both complex cytogenetics (HR = 3.00, 95% CI 1.03–8.68, p = 0.04) and PP (HR = 13.94, 95% CI 5.17–37.62, p < 0.001) had inferior OS. Only primary refractory disease to first-line therapy predicted a higher probability of PP to ibrutinib (RR = 3.77, 95% CI 1.15–12.33, p = 0.03). In this largest study to date evaluating outcomes of R/R MZL treated with ibrutinib, we show that patients with primary refractory disease and those with PP on ibrutinib are very high-risk subsets and need to be prioritized for experimental therapies.
AB - Ibrutinib is effective in the treatment of relapsed/refractory (R/R) marginal zone lymphoma (MZL) with an overall response rate (ORR) of 48%. However, factors associated with response (or lack thereof) to ibrutinib in R/R MZL in clinical practice are largely unknown. To answer this question, we performed a multicenter (25 US centers) cohort study and divided the study population into three groups: “ibrutinib responders”—patients who achieved complete or partial response (CR/PR) to ibrutinib; “stable disease (SD)”; and “primary progressors (PP)”—patients with progression of disease as their best response to ibrutinib. One hundred and nineteen patients met the eligibility criteria with 58%/17% ORR/CR, 29% with SD, and 13% with PP. The median PFS and OS were 29 and 71.4 months, respectively, with no difference in PFS or OS based on the ibrutinib line of therapy or type of therapy before ibrutinib. Patients with complex cytogenetics had an inferior PFS (HR = 3.08, 95% CI 1.23–7.67, p = 0.02), while those with both complex cytogenetics (HR = 3.00, 95% CI 1.03–8.68, p = 0.04) and PP (HR = 13.94, 95% CI 5.17–37.62, p < 0.001) had inferior OS. Only primary refractory disease to first-line therapy predicted a higher probability of PP to ibrutinib (RR = 3.77, 95% CI 1.15–12.33, p = 0.03). In this largest study to date evaluating outcomes of R/R MZL treated with ibrutinib, we show that patients with primary refractory disease and those with PP on ibrutinib are very high-risk subsets and need to be prioritized for experimental therapies.
KW - Ibrutinib
KW - MZL
KW - Marginal zone lymphoma
KW - Refractory
KW - Relapsed
UR - http://www.scopus.com/inward/record.url?scp=85134296031&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85134296031&partnerID=8YFLogxK
U2 - 10.1186/s13045-022-01316-1
DO - 10.1186/s13045-022-01316-1
M3 - Letter
C2 - 35842643
AN - SCOPUS:85134296031
SN - 1756-8722
VL - 15
JO - Journal of Hematology and Oncology
JF - Journal of Hematology and Oncology
IS - 1
M1 - 96
ER -