Abstract
Relapsed indolent lymphoma often becomes refractory to standard chemoimmunotherapy and requires new therapeutic strategies. Targeting the PI3K/mTOR pathway in several types of lymphoma has shown preclinical and clinical efficacy providing the rationale to test this strategy in the treatment of relapsed/refractory indolent lymphomas. We investigated in a phase II open label clinical trial the efficacy and safety of single agent everolimus, an inhibitor of mTORC1, in patients with relapsed/refractory indolent lymphomas. Eligible patients received oral everolimus 10 mg daily on a 28 day-cycle schedule. The primary endpoint was to evaluate the overall response rate (ORR) and safety of single-agent everolimus in this patient population. Fifty-five patients with indolent lymphoma were accrued. The median age was 67 years (range: 33-85) with a median of five prior therapies (range: 1-10). The ORR was 35% (19/55; 95% CI: 24-48%), with complete response unconfirmed in 4% (2/55), and partial response in 31% (17/55). The ORR was 61% (14/23) in the patients with FL. The median time to response was 2.3 months (range: 1.4-14.1), median duration of response of 11.5 months (95%-CI: 5.7-30.4), and a median progression-free survival of 7.2 months (95%-CI: 5.5-12.5). The most common toxicity was hematologic with grades 3-4 anemia, neutropenia, and thrombocytopenia documented in 15% (8/55), 22% (12/55), and 33% (18/55), respectively. There were no cases of febrile neutropenia, and eight patients discontinued therapy because of adverse events. Everolimus monotherapy is a valid therapeutic option in the relapsed and/or refractory indolent non-Hodgkin lymphoma patients and is well tolerated.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 448-453 |
| Number of pages | 6 |
| Journal | American Journal of Hematology |
| Volume | 92 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 1 2017 |
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ASJC Scopus subject areas
- Hematology
Cite this
Efficacy of the oral mTORC1 inhibitor everolimus in relapsed or refractory indolent lymphoma. / Bennani, Nabila; LaPlant, Betsy R.; Ansell, Stephen Maxted; Habermann, Thomas Matthew; Inwards, David J.; Micallef, Ivana; Johnston, Patrick Bruce; Porrata, Luis F.; Colgan, Joseph P.; Markovic, Svetomir Nenad; Nowakowski, Grzegorz S; Macon, William R.; Reeder, Craig B.; Mikhael, Joseph R; Northfelt, Donald W; Ghobrial, Irene M.; Witzig, Thomas Elmer.
In: American Journal of Hematology, Vol. 92, No. 5, 01.05.2017, p. 448-453.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Efficacy of the oral mTORC1 inhibitor everolimus in relapsed or refractory indolent lymphoma
AU - Bennani, Nabila
AU - LaPlant, Betsy R.
AU - Ansell, Stephen Maxted
AU - Habermann, Thomas Matthew
AU - Inwards, David J.
AU - Micallef, Ivana
AU - Johnston, Patrick Bruce
AU - Porrata, Luis F.
AU - Colgan, Joseph P.
AU - Markovic, Svetomir Nenad
AU - Nowakowski, Grzegorz S
AU - Macon, William R.
AU - Reeder, Craig B.
AU - Mikhael, Joseph R
AU - Northfelt, Donald W
AU - Ghobrial, Irene M.
AU - Witzig, Thomas Elmer
PY - 2017/5/1
Y1 - 2017/5/1
N2 - Relapsed indolent lymphoma often becomes refractory to standard chemoimmunotherapy and requires new therapeutic strategies. Targeting the PI3K/mTOR pathway in several types of lymphoma has shown preclinical and clinical efficacy providing the rationale to test this strategy in the treatment of relapsed/refractory indolent lymphomas. We investigated in a phase II open label clinical trial the efficacy and safety of single agent everolimus, an inhibitor of mTORC1, in patients with relapsed/refractory indolent lymphomas. Eligible patients received oral everolimus 10 mg daily on a 28 day-cycle schedule. The primary endpoint was to evaluate the overall response rate (ORR) and safety of single-agent everolimus in this patient population. Fifty-five patients with indolent lymphoma were accrued. The median age was 67 years (range: 33-85) with a median of five prior therapies (range: 1-10). The ORR was 35% (19/55; 95% CI: 24-48%), with complete response unconfirmed in 4% (2/55), and partial response in 31% (17/55). The ORR was 61% (14/23) in the patients with FL. The median time to response was 2.3 months (range: 1.4-14.1), median duration of response of 11.5 months (95%-CI: 5.7-30.4), and a median progression-free survival of 7.2 months (95%-CI: 5.5-12.5). The most common toxicity was hematologic with grades 3-4 anemia, neutropenia, and thrombocytopenia documented in 15% (8/55), 22% (12/55), and 33% (18/55), respectively. There were no cases of febrile neutropenia, and eight patients discontinued therapy because of adverse events. Everolimus monotherapy is a valid therapeutic option in the relapsed and/or refractory indolent non-Hodgkin lymphoma patients and is well tolerated.
AB - Relapsed indolent lymphoma often becomes refractory to standard chemoimmunotherapy and requires new therapeutic strategies. Targeting the PI3K/mTOR pathway in several types of lymphoma has shown preclinical and clinical efficacy providing the rationale to test this strategy in the treatment of relapsed/refractory indolent lymphomas. We investigated in a phase II open label clinical trial the efficacy and safety of single agent everolimus, an inhibitor of mTORC1, in patients with relapsed/refractory indolent lymphomas. Eligible patients received oral everolimus 10 mg daily on a 28 day-cycle schedule. The primary endpoint was to evaluate the overall response rate (ORR) and safety of single-agent everolimus in this patient population. Fifty-five patients with indolent lymphoma were accrued. The median age was 67 years (range: 33-85) with a median of five prior therapies (range: 1-10). The ORR was 35% (19/55; 95% CI: 24-48%), with complete response unconfirmed in 4% (2/55), and partial response in 31% (17/55). The ORR was 61% (14/23) in the patients with FL. The median time to response was 2.3 months (range: 1.4-14.1), median duration of response of 11.5 months (95%-CI: 5.7-30.4), and a median progression-free survival of 7.2 months (95%-CI: 5.5-12.5). The most common toxicity was hematologic with grades 3-4 anemia, neutropenia, and thrombocytopenia documented in 15% (8/55), 22% (12/55), and 33% (18/55), respectively. There were no cases of febrile neutropenia, and eight patients discontinued therapy because of adverse events. Everolimus monotherapy is a valid therapeutic option in the relapsed and/or refractory indolent non-Hodgkin lymphoma patients and is well tolerated.
UR - http://www.scopus.com/inward/record.url?scp=85017555267&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85017555267&partnerID=8YFLogxK
U2 - 10.1002/ajh.24671
DO - 10.1002/ajh.24671
M3 - Article
C2 - 28211162
AN - SCOPUS:85017555267
VL - 92
SP - 448
EP - 453
JO - American Journal of Hematology
JF - American Journal of Hematology
SN - 0361-8609
IS - 5
ER -