Safety and efficacy of Temsirolimus in combination with Bendamustine and Rituximab in relapsed mantle cell and follicular lymphoma

Heß, Georg; Keller, Ulrich; Scholz, Christian W.; Witzens-Harig, Mathias; Atta, Johannes; Buske, Christian; Kirschey, Sebastian; Ruckes, Christian; Medler, Christoph; Oordt, Christina van; Klapper, Wolfram; Theobald, Matthias; Dreyling, Martin

doi:10.1038/leu.2015.60

Cited by 44 publications

(23 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The short life span of the responses indicates that temsirolimus is active in PCNSL, but its activity is often transient, probably due to development of tumor cell resistance. Thus, incorporation of temsirolimus into earlier treatment lines or combining it with other cytostatic drugs or rituximab (as is being done for systemic DLBCL in an ongoing study [NCT01653067 27 ] and has been done in other lymphomas 28,29 ) seems worth consideration. Given the toxicity observed in this study, this should be done in younger patients who are fitter for treatment and using primary antibiotic prophylaxis.…”

Section: Discussionmentioning

confidence: 99%

Phase II Trial of Temsirolimus for Relapsed/Refractory Primary CNS Lymphoma

Korfel

Schlegel

Herrlinger

et al. 2016

JCO

115

View full text Add to dashboard Cite

Purpose In this phase II study (NCT00942747), temsirolimus was tested in patients with relapsed or refractory primary CNS lymphoma (PCNSL). Patients and Methods Immunocompetent adults with histologically confirmed PCNSL after experiencing high-dose methotrexate-based chemotherapy failure who were not eligible for or had experienced high-dose chemotherapy with autologous stem-cell transplant failure were included. The first cohort (n = 6) received 25 mg temsirolimus intravenously once per week. All consecutive patients received 75 mg intravenously once per week. Results Thirty-seven eligible patients (median age, 70 years) were included whose median time since their last treatment was 3.9 months (range, 0.1 to 14.6 months). Complete response was seen in five patients (13.5%), complete response unconfirmed in three (8%), and partial response in 12 (32.4%) for an overall response rate of 54%. Median progression-free survival was 2.1 months (95% CI, 1.1 to 3.0 months). The most frequent Common Toxicity Criteria ≥ 3° adverse event was hyperglycemia in 11 (29.7%) patients, thrombocytopenia in eight (21.6%), infection in seven (19%), anemia in four (10.8%), and rash in three (8.1%). Fourteen blood/CSF pairs were collected in nine patients (10 pairs in five patients in the 25-mg cohort and four pairs in four patients in the 75-mg cohort). The mean maximum blood concentration was 292 ng/mL for temsirolimus and 37.2 ng/mL for its metabolite sirolimus in the 25-mg cohort and 484 ng/mL and 91.1 ng/mL, respectively, in the 75-mg cohort. Temsirolimus CSF concentration was 2 ng/mL in one patient in the 75-mg cohort; in all others, no drug was found in their CSF. Conclusion Single-agent temsirolimus at a weekly dose of 75 mg was found to be active in relapsed/refractory patients with PCNSL; however, responses were usually short lived.

show abstract

Section: Discussionmentioning

confidence: 99%

Phase II Trial of Temsirolimus for Relapsed/Refractory Primary CNS Lymphoma

Korfel

Schlegel

Herrlinger

et al. 2016

JCO

115

View full text Add to dashboard Cite

show abstract

“…An ongoing study currently testing the tolerability of adding bendamustine to this regimen has shown impressive early results with a 100% ORR in (primarily) relapsed MCL patients [92], prompting further accrual [202]. Other NHL histologies have studied lower dose temsirolimus (25 mg weekly), yielding ORRs of 28, 54 and 11% in patients with DLBCL, FL and CLL/SLL, respectively [93].…”

Section: Temsirolimusmentioning

confidence: 98%

Signaling Pathways in Lymphoma: Pathogenesis and Therapeutic Targets

et al. 2013

View full text Add to dashboard Cite

Lymphoma is the fifth most common cancer in the USA. Most lymphomas are classified as non-Hodgkin's lymphoma, and nearly 95% of these cancers are of B-cell origin. B-cell receptor (BCR) surface expression and BCR functional signaling are critical for survival and proliferation of both healthy B cells, as well as most B-lymphoma cells. Agents that inhibit various components of the BCR signaling pathway, as well as parallel signaling pathways, are currently in clinical trials for the treatment of various lymphoma subtypes, including those targeting isoforms of PI3K, mTOR and BTK. In this review, we describe the signaling pathways in healthy mature B cells, the aberrant signaling in lymphomatous B cells and the rationale for clinical trials of agents targeting these pathways as well as the results of clinical trials to date. We propose that the entry into a kinase inhibitor era of lymphoma therapy will be as transformative for our patients as the advent of the antibody or chemotherapy era before it.

show abstract

“…The most frequent grades 3 and 4 adverse events were thrombocytopenia (44%), neutropenia (26%), gastrointestinal toxicities (15%), and lymphopenia (15%). Most recently, an ongoing study examining the combination of temsirolimus with br reported a preliminary orr of 88% with that combination in patients having relapsed non-bendamustinerefractory fl 35 . Median pfs has not been reached after a median follow-up of 13 months.…”

Section: Mtor Inhibitorsmentioning

confidence: 99%

Emerging Therapies for the Treatment of Relapsed or Refractory Follicular Lymphoma

et al. 2016

View full text Add to dashboard Cite

With no treatment standard having been established for relapsed and refractory follicular lymphoma, a number of therapeutic approaches are used in Canada. In patients who relapse early or who eventually become resistant to subsequent treatment, prognosis is poor, and new approaches are needed. A number of novel therapies are being examined in this setting, including monoclonal antibodies, immunoconjugates, immunomodulatory agents, and signal transduction inhibitors. With the body of evidence for those emerging therapies accumulating and the standard upfront treatment changing from rituximab and chop (cyclophosphamide-doxorubicin-vincristine-prednisone) or rituximab and cvp (cyclophosphamide-vincristine-prednisone) to bendamustine and rituximab, treatment decisions in the relapsed and refractory setting have become more complex. The choice of subsequent treatment must consider type of upfront treatment; duration of remission; and patient-related factors such as age, comorbidities, and treatment preferences. This paper summarizes the evidence for novel therapies and proposes recommendations for subsequent treatment options by remission duration after induction and maintenance.

show abstract

Safety and efficacy of Temsirolimus in combination with Bendamustine and Rituximab in relapsed mantle cell and follicular lymphoma

Cited by 44 publications

References 41 publications

Phase II Trial of Temsirolimus for Relapsed/Refractory Primary CNS Lymphoma

Phase II Trial of Temsirolimus for Relapsed/Refractory Primary CNS Lymphoma

Signaling Pathways in Lymphoma: Pathogenesis and Therapeutic Targets

Emerging Therapies for the Treatment of Relapsed or Refractory Follicular Lymphoma

Contact Info

Product

Resources

About