Real‐world outcomes of ibrutinib therapy in Korean patients with relapsed or refractory mantle cell lymphoma: a multicenter, retrospective analysis

Abstract

Dear Editor, Despite the introduction of novel front-line therapies including rituximab plus high-dose cytarabine followed by consolidative autologous stem cell transplantation (ASCT) and salvage therapy with bendamustine, lenalidomide or bortezomib, mantle cell lymphoma (MCL) is still considered incurable and most patients experience relapse or refractory (RR) disease. Ibrutinib (Imbruvica R) is a firstin-class oral agent that mainly works by inhibiting Bruton's tyrosine kinase and is considered the standard of care for RR MCL. However, reports for outcomes and safety profiles of ibrutinib treatment in Asian RR MCL patients are limited as MCL accounts for less than 3% of Non-Hodgkin's lymphomas in Asia [1, 2]. To evaluate the realworld outcomes of ibrutinib therapy in RR MCL patients in Korea, we performed a retrospective analysis of patients with RR MCL who were treated with ibrutinib from 18 tertiary institutes (details are provided in the Supplementary Materials). A total of 88 patients were analyzed. Their immunophenotypic and cytogenetics features at the time of diagnosis are shown in Supplementary Table S1. 71 (80.7%) patients were male. Three (3.4%) patients had blastoid variants MCL. At the time of initial diagnosis, their median age was 67 (range: 40-90) years. A total of 11 (12.5%) patients were classified as stage II and 77 (87.5%) as stage III-IV. All patients received combination chemotherapy with or without rituximab as front-line treatment. Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) was the most frequently used regimen (n = 59, 67.0%), followed by rituximab plus fractionated cyclophosphamide, vincristine, doxorubicin, and

IBRORS-MCL study: a Spanish retrospective and observational study of relapsed/refractory mantle-cell lymphoma treated with ibrutinib in routine clinical practice

“…It is also worth mentioning that the median OS of 32 months is comparable to the one obtained in the clinical trial setting (26.7 months) and that the PFS of 20 months was superior, with similar median treatment exposure [ 10 ]. The median PFS and OS we observed are similar to the Korean cohorts published by Jeon et al (27 and 35 months) [ 13 ] and Yi et al (20.8 and NR) [ 16 ], with around 16 months of median treatment exposure, and compare favorably with those from the UK cohorts by Tucker et al (18.5 and 12 months) and McCulloch et al (17.8 and 23.9 months) with 10 months of median treatment exposure, and the Italian cohort (12.9 and 16 months) [ 11 ], with 6 months of median ibrutinib exposure.…”

“…Although not directly comparable to the clinical trial setting, the CR rate observed in the present study (38%) is higher than that observed in the pooled analysis (27%) [ 10 ] and similar observational studies (ranging from 15 to 27%) [ 11 , 13 , 14 ]. This is probably due to a larger proportion of patients in our study receiving 1–2 prior lines, which supports previous evidence showing better outcomes when ibrutinib is used in earlier lines of therapy [ 6 , 16 ] as well as the increased presence of poor prognostic factors with increasing lines of therapy [ 17 ]. Lower-risk disease (76% with low-intermediate sMIPI) and better performance in our patients (94% with an ECOG PS 0–1) compared to other real-world cohorts [ 11 , 13 , 15 ] may have also contributed to these observations.…”

“…This real-world analysis showed that ibrutinib treatment yields a high response rate and favorable outcomes in terms of PFS and OS in patients with R/R MCL. The ORR of 64% is consistent with that obtained in the extended 3.5 years follow-up from the pooled analysis with 370 patients treated in the clinical trial setting (ORR 69.7%) [ 10 ] and other real-life retrospective studies by Jeon et al (64%) [ 13 ], Epperla et al (65%) [ 12 ], Yi et al (64.8%) [ 16 ] and McCulloch et al (69%) [ 14 ]. Although not directly comparable to the clinical trial setting, the CR rate observed in the present study (38%) is higher than that observed in the pooled analysis (27%) [ 10 ] and similar observational studies (ranging from 15 to 27%) [ 11 , 13 , 14 ].…”

“…Lower-risk disease (76% with low-intermediate sMIPI) and better performance in our patients (94% with an ECOG PS 0–1) compared to other real-world cohorts [ 11 , 13 , 15 ] may have also contributed to these observations. Conversely, the proportion of patients with blastoid variant (24%), a well-known adverse prognostic factor, was higher in our cohort than in the clinical trial setting (12%) [ 10 ], and real-life Korean (3.4%) [ 16 ], Italian (3.9%) [ 11 ], and UK cohorts (14–18%) [ 14 , 15 ].…”

“…The PFS and OS benefits obtained with ibrutinib in clinical trials have also been observed in the real-world setting [ 11 – 16 ], but the need remains for more real-world studies to reaffirm the use of ibrutinib as standard of care for patients with R/R MCL. In this real-world observational study, we describe the clinical characteristics, management and outcomes of patients with R/R MCL receiving ibrutinib in routine clinical practice in Spain.…”