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Combination trial of duvelisib (IPI-145) with rituximab or bendamustine/rituximab in patients with non-Hodgkin lymphoma or chronic lymphocytic leukemia.
Am J Hematol. 2019 12; 94(12):1325-1334.AJ

Abstract

Duvelisib, a potent δ- and γ-PI3K inhibitor, is a potential therapeutic for hematologic malignancies. Rituximab and bendamustine have demonstrated activity in non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Combining duvelisib with either rituximab alone or rituximab and bendamustine may improve response rates and remission durability. We conducted this Phase one study in relapsed/refractory NHL and CLL patients. During expansion, each arm enrolled to disease-specific cohorts to assess efficacy. Arm one received rituximab 375 mg/m2 IV weekly for two 4-week cycles plus duvelisib until progression/intolerance. Arm two received rituximab 375 mg/m2 IV Day one, bendamustine 90 mg/m2 IV (NHL patients) or 70 mg/m2 IV (CLL patients) Days one-two for six cycles, plus duvelisib until progression/intolerance. Duvelisib doses of 50 mg and 75 mg BID were tested during dose escalation. Forty-six patients (27 NHL, 19 CLL) were treated. The adverse events of the drug combinations were consistent with single agent toxicities. The most common AEs were neutropenia (47.7%), fatigue (41.3%), and rash (41.3%). A duvelisib expansion dose of 25 mg BID was chosen based on the monotherapy phase one study, IPI-145-02, which confirmed that dose for further clinical development. Overall response rate was 71.8%. Median progression-free survival was 13.7 months. Median overall survival has not been reached, but 30-month overall survival probability was 62%. Duvelisib combined with rituximab, or bendamustine and rituximab did not appear to increase toxicities beyond the known safety profile of the individual agents. Further study is needed to determine if these combinations improve efficacy.

Authors+Show Affiliations

Sarah Cannon Research Institute, Nashville, Tennessee. Tennessee Oncology, PLLC, Nashville, Tennessee.Sarah Cannon Research Institute, Nashville, Tennessee. Department of Hematology and Oncology, Stephenson Cancer Center, Oklahoma City, Oklahoma.Sarah Cannon Research Institute, Nashville, Tennessee. Colorado Blood Cancer Institute, Denver, Colorado.Sarah Cannon Research Institute, Nashville, Tennessee. Colorado Blood Cancer Institute, Denver, Colorado.Sarah Cannon Research Institute, Nashville, Tennessee. Tennessee Oncology, PLLC, Nashville, Tennessee.Sarah Cannon Research Institute, Nashville, Tennessee. Florida Cancer Specialists, Sarasota, Florida.

Pub Type(s)

Clinical Trial, Phase I
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31490009

Citation

Flinn, Ian W., et al. "Combination Trial of Duvelisib (IPI-145) With Rituximab or Bendamustine/rituximab in Patients With non-Hodgkin Lymphoma or Chronic Lymphocytic Leukemia." American Journal of Hematology, vol. 94, no. 12, 2019, pp. 1325-1334.
Flinn IW, Cherry MA, Maris MB, et al. Combination trial of duvelisib (IPI-145) with rituximab or bendamustine/rituximab in patients with non-Hodgkin lymphoma or chronic lymphocytic leukemia. Am J Hematol. 2019;94(12):1325-1334.
Flinn, I. W., Cherry, M. A., Maris, M. B., Matous, J. V., Berdeja, J. G., & Patel, M. (2019). Combination trial of duvelisib (IPI-145) with rituximab or bendamustine/rituximab in patients with non-Hodgkin lymphoma or chronic lymphocytic leukemia. American Journal of Hematology, 94(12), 1325-1334. https://doi.org/10.1002/ajh.25634
Flinn IW, et al. Combination Trial of Duvelisib (IPI-145) With Rituximab or Bendamustine/rituximab in Patients With non-Hodgkin Lymphoma or Chronic Lymphocytic Leukemia. Am J Hematol. 2019;94(12):1325-1334. PubMed PMID: 31490009.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Combination trial of duvelisib (IPI-145) with rituximab or bendamustine/rituximab in patients with non-Hodgkin lymphoma or chronic lymphocytic leukemia. AU - Flinn,Ian W, AU - Cherry,Mohamad A, AU - Maris,Michael B, AU - Matous,Jeffrey V, AU - Berdeja,Jesus G, AU - Patel,Manish, Y1 - 2019/10/04/ PY - 2019/04/04/received PY - 2019/08/14/revised PY - 2019/09/03/accepted PY - 2019/9/7/pubmed PY - 2020/4/14/medline PY - 2019/9/7/entrez SP - 1325 EP - 1334 JF - American journal of hematology JO - Am. J. Hematol. VL - 94 IS - 12 N2 - Duvelisib, a potent δ- and γ-PI3K inhibitor, is a potential therapeutic for hematologic malignancies. Rituximab and bendamustine have demonstrated activity in non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Combining duvelisib with either rituximab alone or rituximab and bendamustine may improve response rates and remission durability. We conducted this Phase one study in relapsed/refractory NHL and CLL patients. During expansion, each arm enrolled to disease-specific cohorts to assess efficacy. Arm one received rituximab 375 mg/m2 IV weekly for two 4-week cycles plus duvelisib until progression/intolerance. Arm two received rituximab 375 mg/m2 IV Day one, bendamustine 90 mg/m2 IV (NHL patients) or 70 mg/m2 IV (CLL patients) Days one-two for six cycles, plus duvelisib until progression/intolerance. Duvelisib doses of 50 mg and 75 mg BID were tested during dose escalation. Forty-six patients (27 NHL, 19 CLL) were treated. The adverse events of the drug combinations were consistent with single agent toxicities. The most common AEs were neutropenia (47.7%), fatigue (41.3%), and rash (41.3%). A duvelisib expansion dose of 25 mg BID was chosen based on the monotherapy phase one study, IPI-145-02, which confirmed that dose for further clinical development. Overall response rate was 71.8%. Median progression-free survival was 13.7 months. Median overall survival has not been reached, but 30-month overall survival probability was 62%. Duvelisib combined with rituximab, or bendamustine and rituximab did not appear to increase toxicities beyond the known safety profile of the individual agents. Further study is needed to determine if these combinations improve efficacy. SN - 1096-8652 UR - https://www.unboundmedicine.com/medline/citation/31490009/Combination_trial_of_duvelisib__IPI_145__with_rituximab_or_bendamustine/rituximab_in_patients_with_non_Hodgkin_lymphoma_or_chronic_lymphocytic_leukemia_ L2 - https://doi.org/10.1002/ajh.25634 DB - PRIME DP - Unbound Medicine ER -