Impressive response to temsirolimus in a patient with chemotherapy refractory diffuse large B-cell non-Hodgkin's lymphoma


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Impressive response to temsirolimus in a patient with
chemotherapy refractory diffuse large B-cell

non-Hodgkin’s lymphoma
Philipp Kiewe, Eckhard Thiel

To cite this version:
Philipp Kiewe, Eckhard Thiel. Impressive response to temsirolimus in a patient with chemotherapy
refractory diffuse large B-cell non-Hodgkin’s lymphoma. Annals of Hematology, Springer Verlag, 2010,
90 (1), pp.109-110. �10.1007/s00277-010-0951-z�. �hal-00554984�

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                             Editorial Manager(tm) for Annals of Hematology 
                                  Manuscript Draft 
 
 
Manuscript Number: AOHE-D-10-00147 
 
Title: Impressive response to temsirolimus in a patient with chemotherapy refractory diffuse large B-
cell non-Hodgkin's lymphoma 
 
Article Type: Letter to the Editor 
 
Keywords: Temsirolimus; DLCBL; aggressive lymphoma 
 
Corresponding Author: Dr. Philipp Kiewe, M.D. 
 
Corresponding Author's Institution: Charité Campus Benjamin Franklin 
 
First Author: Philipp Kiewe, M.D. 
 
Order of Authors: Philipp Kiewe, M.D.; Eckhard Thiel, M.D. 
 
Abstract: No Abstract - letter to the editor 
 
 
 
 



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- 1 - 

Impressive response to temsirolimus in a patient with chemotherapy refractory 

diffuse large B-cell non-Hodgkin’s lymphoma 

 

Philipp Kiewe
*
 and Eckhard Thiel 

Dept. of Hematology, Oncology and Transfusion Medicine, Charité University 

Medicine, Campus Benjamin Franklin, Hindenburgdamm 30/31, 12200 Berlin, 

Germany 

 

*Charité University Medicine, Campus Benjamin Franklin 

Dept. of Hematology, Oncology and Transfusion Medicine 

Hindenburgdamm 30 

D-12200 Berlin, Germany 

Tel.: +49-30-8445-2337 

Fax: +49-30-8445-4468 

Email: philipp.kiewe@charite.de 

 

Keywords: Temsirolimus; DLCBL; aggressive lymphoma

Manuscript
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- 2 - 

Dear Editor, 

Temsirolimus is a selective inhibitor of the cell proliferation promoting intracellular 

protein mTOR (mammalian target of rapamycin). Its activity in lymphatic 

malignancies has first been demonstrated in relapsed mantle-cell lymphoma [1]. 

Further studies confirmed activity in this lymphoma entity and established a weekly 

dosage of 75mg as approved treatment regimen [2], although a weekly dose of 25mg 

remains an effective treatment option [3]. Experience with temsirolimus in other 

entities of NHL is limited to a phase II study in recurrent DLCBL, follicular lymphoma 

and chronic lymphocytic leukemia/small lymphocytic lymphoma [4]. In 19 evaluable 

patients with DLCBL and a median of ≥ 2 prior treatment lines, a remarkable overall 

response rate of 42% was observed with a weekly temsirolimus dosage of only 

25mg. 

 

A 44-year old woman was diagnosed with diffuse-large B-cell Non-Hodgkin’s 

lymphoma (NHL) limited to the tongue base (stage IBE) in June 2003. After initial 

treatment with 6 cycles of dose-intensified cyclophosphamide, adriamycin, vincristine, 

etoposide and prednisolone (Hi-CHOEP), a complete response was achieved. The 

patient relapsed in October 2006 with intrathoracic and abdominal manifestations. 

Salvage therapy included 3 cycles of rituximab, ifosfamide, carboplatin and etoposide 

(R-ICE) followed by high-dose carmustine, etoposide, cytarabine, melphalan (HD-

BEAM) and autologous stem-cell transplantation resulting in complete response. In 

July 2008, second relapse occurred with cervical and abdominal lymph node 

enlargements. Treatment was initiated with 5 cycles of rituximab and bendamustine 

yielding another complete response. Remission, however, was short-lived, and in 

January 2009 disease recurred. Sequential treatment included one cycle of rituximab, 

dexamethasone, high-dose cytarabine, cisplatin (R-DHAP) and one cycle of 



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- 3 - 

rituximab, high-dose cytarabine, mitoxantrone (dose-modified R-HAM) in reconfirmed 

CD20-positive disease followed by a second high-dose protocol with 
90

Y-ibritumomab 

tiuxetan, cyclophosphamide, etoposide, carmustine (Z-CVB) and autologous stem-

cell support. This time, only partial remission was achieved with disease progression 

shortly thereafter in August 2009. Further treatment lines including lenalidomide, two 

cycles each of gemcitabine/mitoxantrone and carboplatin/ifosfamide were ineffective. 

In November 2009 the patient presented with a large intraabdominal tumor-bulk 

resulting in a massively distended abdomen. Lactate dehydrogenase (LDH) had risen 

to 480 U/L (< 247) and bone marrow function was poor with severe tricytopenia, 

predominantly thrombocytopenia of 50 x 10
9
/l (150-400). 

At this time, weekly monotherapy with 25mg temsirolimus was started. A dramatic 

clinical response was seen after only 5 infusions with normalization of the abdominal 

exam and LDH. No relevant toxicity was noted. The sixth temsirolimus infusion was 

combined with bendamustine after platelet counts had risen to 136 x 10
9
/l. One week 

thereafter, restaging computed tomography (CT) scans confirmed clinical response 

with only minimal residual abdominal lymphoma manifestations compared with pre-

treatment imaging (Fig 1a+b). Temsirolimus infusions were continued but 

unfortunately, tumor progression was observed four weeks later. 

 

The very favourable response in our patient with highly pretreated refractory DLCBL, 

though short-lived, supports the evidence of a high activity of temisirolimus in NHL 

including DLCBL. Further investigations are clearly warranted, preferably in less 

advanced disease and in combination with chemotherapy. Moreover, the optimal 

dosage needs to be defined. 

 



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- 4 - 

Figure 1 Abdominal CT scan without intravenous contrast-enhancement before 

temsirolimus treatment (a) and after six weekly infusions (b) showing only minimal 

residual lymphoma manifestations (arrow). 

 

References: 

1.  Witzig TE, Geyer SM, Ghobrial I, et al (2005) Phase II trial of single-agent 

temsirolimus (CCI-779) for relapsed mantle cell lymphoma. J Clin Oncol 23:5347-

5356.  

2.  Hess G, Herbrecht R, Romaguera J, et al (2009) Phase III study to evaluate 

temsirolimus compared with investigator’s choice therapy for the treatment of 

relapsed or refractory mantle cell lymphoma. J Clin Oncol 27:3822-3829. 

3.  Ansell SM, Inwards DJ, Rowland KM Jr, et al (2008) Low-dose, single-agent 

temsirolimus for relapsed mantle cell lymphoma: a phase 2 trial in the North Central 

Cancer Treatment Group. Cancer 113:508-514. 

4.  Smith SM, Pro B, Cisneros A, et al (2008) Activity of single agent temsirolimus 

(CCI-779) in non-mantle cell non-Hodgkin lymphoma subtypes. J Clin Oncol 26:15s 

(suppl; abstr 8514). 

 

http://www.ncbi.nlm.nih.gov/pubmed/18543327?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
http://www.ncbi.nlm.nih.gov/pubmed/18543327?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
http://www.ncbi.nlm.nih.gov/pubmed/18543327?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum


Figure 1 a+b
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