Ibrutinib versus temsirolimus: 3-year follow-up of patients with previously treated mantle cell lymphoma from the phase 3, international, randomized, open-label RAY study

Rule, Simon; Jurczak, Wojciech; Jerkeman, Mats; Rusconi, Chiara; Trněný, Marek; Offner, Fritz; Caballero, Dolores; Joao, C.; Witzens-Harig, Mathias; Heß, Georg; Bence‐Bruckler, Isabelle; Cho, S.-G.; Thiéblemont, Catherine; Zhou, Wangda; Henninger, T.; Goldberg, Judith D.; Vermeulen, Jessica; Dreyling, Martin

doi:10.1038/s41375-018-0023-2

Cited by 77 publications

(67 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Single agent ibrutinib alone has been shown to be superior to temsirolimus in a randomized phase 3 clinical trial ( n = 280) (Dreyling et al , ). Furthermore, results with the IR combination are favourable in RR‐MCL (88% ORR and 58% CR) when compared to other agents, such as lenalidomide [ORR of 28% and 7·5% CR in the EMERGE trial (Goy et al , ) and in a phase II study with rituximab (Wang et al , ), ORR was 57% and 36% CR], temsirolimus alone [ORR of 22–47% in two studies respectively (Hess et al , ; Rule et al , )] or in combination with rituximab (Atilla et al , ) and in idelalisib (ORR of 40% and CR of 5%) (Kahl et al , ). With these encouraging results with IR, we have initiated a frontline trial in MCL, with IR as induction therapy followed by consolidation with hyper‐CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone plus methotrexate and cytarabine)‐based regimens – (NCT02427620).…”

Section: Discussionmentioning

confidence: 99%

Four‐year follow‐up of a single arm, phase II clinical trial of ibrutinib with rituximab (IR) in patients with relapsed/refractory mantle cell lymphoma (MCL)

et al. 2018

View full text Add to dashboard Cite

Ibrutinib has shown significant activity in patients with relapsed or refractory mantle cell lymphoma (RR-MCL). We report the long-term outcome and safety profile of a single-centre, single arm, open-label, phase 2 study of RR-MCL treated with IR. Overall, the median follow-up time was 47 months (range 1-52 months), median duration on treatment was 16 months (range 1-53 months) and median number of treatment cycles was 17 (range 1-56). Twenty-nine patients (58%) achieved complete remission and of these, 12 patients continue on study. Thirty-eight patients discontinued treatment, 14 due to disease progression (2 transformed). Patients with blastoid morphology, high risk MCL International Prognostic Index score and high Ki67% had inferior survival. The commonest grade 1-2 toxicities were fatigue, diarrhoea, nausea, arthralgias and myalgias. None had long term toxicities. Median progression-free survival was 43 months. Eighteen patients (36%) died (14 deaths were MCL-related). The median overall survival has not been reached. Treatment with IR can provide durable remissions in a subset of patients with RR-MCL, especially those with low Ki67%. The possible benefit of adding other therapies in combination with IR in RR-MCL is under exploration.

show abstract

Section: Discussionmentioning

confidence: 99%

Four‐year follow‐up of a single arm, phase II clinical trial of ibrutinib with rituximab (IR) in patients with relapsed/refractory mantle cell lymphoma (MCL)

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Ibrutinib monotherapy demonstrated an ORR of 68%, a CR rate of 21%, and a median PFS of 13.9 months, with an additional benefit demonstrated with the addition of rituximab (ORR 87%; CR 38%; 15-month PFS 69%) [63,64]. In the 3-year follow-up of the RAY study, ibrutinib showed a favorable OS trend versus temsirolimus (median OS 30.3 versus 23.5 months; hazard ratio [HR] 0.74 [95% CI 0.54-1.02], P = 0.0621), with the most benefit seen in patients receiving only one prior line of therapy [68]. In addition, in a pooled analysis after an extended 3.5-year follow-up of phase II and III clinical trials of patients with relapsed/refractory MCL, those who received second-line therapy and those achieving a CR derived the greatest benefit from ibrutinib treatment; median PFS and OS were 12.5 and 26.7 months, respectively [69].…”

Section: Relapsed/refractory Diseasementioning

confidence: 99%

Treatment of mantle cell lymphoma in Asia: a consensus paper from the Asian Lymphoma Study Group

et al. 2020

View full text Add to dashboard Cite

Background: Mantle cell lymphoma (MCL) is a B cell malignancy that can be aggressive and with a poor prognosis; the clinical course is heterogeneous. The epidemiology of MCL in Asia is not well documented but appears to comprise 2-6% of all lymphoma cases based on available data, with variation observed between countries. Although international guidelines are available for the treatment of MCL, there is a lack of published data or guidance on the clinical characteristics and management of MCL in patient populations from Asia. This paper aims to review the available treatment and, where clinical gaps exist, provide expert consensus from the Asian Lymphoma Study Group (ALSG) on appropriate MCL management in Asia. Body: Management strategies for MCL are patient-and disease stage-specific and aim to achieve balance between efficacy outcomes and toxicity. For asymptomatic patients with clearly indolent disease, observation may be an appropriate strategy. For stage I/II disease, following international guidelines is appropriate, which include either a short course of conventional chemotherapy followed by consolidated radiotherapy, less aggressive chemotherapy regimens, or a combination of these approaches. For advanced disease, the approach is based on the age and fitness of the patient. For young, fit patients, the current practice for induction therapy differs across Asia, with cytarabine having an important role in this setting. Hematopoietic stem cell transplantation (HSCT) may be justified in selected patients because of the high relapse risk. In elderly patients, specific chemoimmunotherapy regimens available in each country/region are a treatment option. For maintenance therapy after first-line treatment, the choice of approach should be individualized, with cost being an important consideration within Asia. For relapsed/ refractory disease, ibrutinib should be considered as well as other follow-on compounds, if available. Conclusion: Asian patient-specific data for the treatment of MCL are lacking, and the availability of treatment options differs between country/region within Asia. Therefore, there is no clear one-size-fits-all approach and further investigation on the most appropriate sequence of treatment that should be considered for this heterogeneous disease.

show abstract

“…It has been approved by FDA for the treatment of chronic lymphocytic leukemia (CLL) [9] and mantle cell lymphoma (MCL) [10] in all lines of therapy. Moreover, ibrutinib has been used widely in different types of B malignancies of the lymphatic system [11][12][13]. Although the overall response rates (ORR) to ibrutinib in CLL or MCL patients is high, the complete response (CR) rate is low, and some patients experience disease progression while receiving ibrutinib [14,15].…”

Section: Introductionmentioning

confidence: 99%

Synergistic effect of ibrutinib and CD19 CAR-T cells on Raji cells in vivo and in vitro

Liu

Wang

Zheng

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

Ibrutinib versus temsirolimus: 3-year follow-up of patients with previously treated mantle cell lymphoma from the phase 3, international, randomized, open-label RAY study

Cited by 77 publications

References 9 publications

Four‐year follow‐up of a single arm, phase II clinical trial of ibrutinib with rituximab (IR) in patients with relapsed/refractory mantle cell lymphoma (MCL)

Four‐year follow‐up of a single arm, phase II clinical trial of ibrutinib with rituximab (IR) in patients with relapsed/refractory mantle cell lymphoma (MCL)

Treatment of mantle cell lymphoma in Asia: a consensus paper from the Asian Lymphoma Study Group

Synergistic effect of ibrutinib and CD19 CAR-T cells on Raji cells in vivo and in vitro

Contact Info

Product

Resources

About