Long-term outcomes in patients with relapsed or refractory hairy cell leukemia treated with vemurafenib monotherapy

Shivani Handa; Jeong Ok Lee; Andriy Derkach; Richard M. Stone; Alan Saven; Jessica K. Altman; Michael R. Grever; Kanti R. Rai; Madhulika Shukla; Shreya Vemuri; Skye Montoya; Justin Taylor; Omar Abdel-Wahab; Martin S. Tallman; Jae H. Park

doi:10.1182/blood.2022016183

Long-term outcomes in patients with relapsed or refractory hairy cell leukemia treated with vemurafenib monotherapy

Shivani Handa, Jeong Ok Lee, Andriy Derkach, Richard M. Stone, Alan Saven, Jessica K. Altman, Michael R. Grever, Kanti R. Rai, Madhulika Shukla, Shreya Vemuri, Skye Montoya, Justin Taylor, Omar Abdel-Wahab, Martin S. Tallman, Jae H. Park^*

^*Corresponding author for this work

Medicine, Hematology Oncology Division

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

Abstract

Vemurafenib, an oral BRAF inhibitor, has demonstrated high response rates in relapsed/refractory (R/R) hairy cell leukemia (HCL). However, little is known about long-term outcomes and response to retreatment. Herein, we report the results of 36 patients with R/R HCL treated with vemurafenib from the United States arm of the phase 2 clinical trial (NCT01711632). The best overall response rate was 86%, including 33% complete response (CR) and 53% partial response (PR). After a median follow-up of 40 months, 21 of 31 responders (68%) experienced relapse with a median relapse-free survival (RFS) of 19 months (range, 12.5-53.9 months). There was no significant difference in the RFS for patients with CR vs PR. Fourteen of 21 (67%) relapsed patients were retreated with vemurafenib, with 86% achieving complete hematologic response. Two patients acquired resistance to vemurafenib with the emergence of new KRAS and CDKN2A mutations, respectively. Six of 12 (50%) responders to vemurafenib retreatment experienced another relapse with a median RFS of 12.7 months. Overall survival (OS) was 82% at 4 years, with a significantly shorter OS in patients who relapsed within 1 year of initial treatment with vemurafenib. Higher cumulative doses or a longer duration of treatment did not lengthen the durability of response. All adverse events in the retreatment cohort were grade 1/2 except for 1 case of a grade 3 rash and 1 grade 3 fever/pneumonia. Our data suggest that vemurafenib retreatment is a safe and effective option for patients with R/R HCL.

Original language	English (US)
Pages (from-to)	2663-2671
Number of pages	9
Journal	Blood
Volume	140
Issue number	25
DOIs	https://doi.org/10.1182/blood.2022016183
State	Published - Dec 22 2022

Funding

This work was supported by the NIH/NCI 1P50 254838-01 (O.A.-W. and M.S.T.) and the Hairy Cell Leukemia Foundation / Leukemia & Lymphoma Society Synergistic Team Award. This work was supported by the NIH/NCI 1P50 254838-01 (O.A.-W. and M.S.T.) and the Hairy Cell Leukemia Foundation/Leukemia & Lymphoma Society Synergistic Team Award. Contribution: J.H.P. designed the study and wrote the manuscript; S.H. J.-O.L. and J.H.P. collected the data, conducted the analysis, and wrote the manuscript; R.M.S. A.S. J.K.A. M.R.G. K.R.R. O.A.-W. M.S.T. and J.H.P. enrolled patients to the clinical trial and took care of the patients; M.S. and S.V. participated in data collection; A.D. conducted the statistical analysis; S.M. J.T. and O.A.-W. conducted the genomic analysis; and all the authors reviewed and approved the manuscript.

ASJC Scopus subject areas

Biochemistry
Immunology
Hematology
Cell Biology

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10.1182/blood.2022016183

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Handa, S., Lee, J. O., Derkach, A., Stone, R. M., Saven, A., Altman, J. K., Grever, M. R., Rai, K. R., Shukla, M., Vemuri, S., Montoya, S., Taylor, J., Abdel-Wahab, O., Tallman, M. S., & Park, J. H. (2022). Long-term outcomes in patients with relapsed or refractory hairy cell leukemia treated with vemurafenib monotherapy. Blood, 140(25), 2663-2671. https://doi.org/10.1182/blood.2022016183

@article{b151b3ffeb494900aec36a6f00c37b5b,

title = "Long-term outcomes in patients with relapsed or refractory hairy cell leukemia treated with vemurafenib monotherapy",

abstract = "Vemurafenib, an oral BRAF inhibitor, has demonstrated high response rates in relapsed/refractory (R/R) hairy cell leukemia (HCL). However, little is known about long-term outcomes and response to retreatment. Herein, we report the results of 36 patients with R/R HCL treated with vemurafenib from the United States arm of the phase 2 clinical trial (NCT01711632). The best overall response rate was 86%, including 33% complete response (CR) and 53% partial response (PR). After a median follow-up of 40 months, 21 of 31 responders (68%) experienced relapse with a median relapse-free survival (RFS) of 19 months (range, 12.5-53.9 months). There was no significant difference in the RFS for patients with CR vs PR. Fourteen of 21 (67%) relapsed patients were retreated with vemurafenib, with 86% achieving complete hematologic response. Two patients acquired resistance to vemurafenib with the emergence of new KRAS and CDKN2A mutations, respectively. Six of 12 (50%) responders to vemurafenib retreatment experienced another relapse with a median RFS of 12.7 months. Overall survival (OS) was 82% at 4 years, with a significantly shorter OS in patients who relapsed within 1 year of initial treatment with vemurafenib. Higher cumulative doses or a longer duration of treatment did not lengthen the durability of response. All adverse events in the retreatment cohort were grade 1/2 except for 1 case of a grade 3 rash and 1 grade 3 fever/pneumonia. Our data suggest that vemurafenib retreatment is a safe and effective option for patients with R/R HCL.",

author = "Shivani Handa and Lee, {Jeong Ok} and Andriy Derkach and Stone, {Richard M.} and Alan Saven and Altman, {Jessica K.} and Grever, {Michael R.} and Rai, {Kanti R.} and Madhulika Shukla and Shreya Vemuri and Skye Montoya and Justin Taylor and Omar Abdel-Wahab and Tallman, {Martin S.} and Park, {Jae H.}",

note = "Publisher Copyright: {\textcopyright} 2022 The American Society of Hematology",

year = "2022",

month = dec,

day = "22",

doi = "10.1182/blood.2022016183",

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Handa, S, Lee, JO, Derkach, A, Stone, RM, Saven, A, Altman, JK, Grever, MR, Rai, KR, Shukla, M, Vemuri, S, Montoya, S, Taylor, J, Abdel-Wahab, O, Tallman, MS & Park, JH 2022, 'Long-term outcomes in patients with relapsed or refractory hairy cell leukemia treated with vemurafenib monotherapy', Blood, vol. 140, no. 25, pp. 2663-2671. https://doi.org/10.1182/blood.2022016183

TY - JOUR

T1 - Long-term outcomes in patients with relapsed or refractory hairy cell leukemia treated with vemurafenib monotherapy

AU - Handa, Shivani

AU - Lee, Jeong Ok

AU - Derkach, Andriy

AU - Stone, Richard M.

AU - Saven, Alan

AU - Altman, Jessica K.

AU - Grever, Michael R.

AU - Rai, Kanti R.

AU - Shukla, Madhulika

AU - Vemuri, Shreya

AU - Montoya, Skye

AU - Taylor, Justin

AU - Abdel-Wahab, Omar

AU - Tallman, Martin S.

AU - Park, Jae H.

PY - 2022/12/22

Y1 - 2022/12/22

N2 - Vemurafenib, an oral BRAF inhibitor, has demonstrated high response rates in relapsed/refractory (R/R) hairy cell leukemia (HCL). However, little is known about long-term outcomes and response to retreatment. Herein, we report the results of 36 patients with R/R HCL treated with vemurafenib from the United States arm of the phase 2 clinical trial (NCT01711632). The best overall response rate was 86%, including 33% complete response (CR) and 53% partial response (PR). After a median follow-up of 40 months, 21 of 31 responders (68%) experienced relapse with a median relapse-free survival (RFS) of 19 months (range, 12.5-53.9 months). There was no significant difference in the RFS for patients with CR vs PR. Fourteen of 21 (67%) relapsed patients were retreated with vemurafenib, with 86% achieving complete hematologic response. Two patients acquired resistance to vemurafenib with the emergence of new KRAS and CDKN2A mutations, respectively. Six of 12 (50%) responders to vemurafenib retreatment experienced another relapse with a median RFS of 12.7 months. Overall survival (OS) was 82% at 4 years, with a significantly shorter OS in patients who relapsed within 1 year of initial treatment with vemurafenib. Higher cumulative doses or a longer duration of treatment did not lengthen the durability of response. All adverse events in the retreatment cohort were grade 1/2 except for 1 case of a grade 3 rash and 1 grade 3 fever/pneumonia. Our data suggest that vemurafenib retreatment is a safe and effective option for patients with R/R HCL.

AB - Vemurafenib, an oral BRAF inhibitor, has demonstrated high response rates in relapsed/refractory (R/R) hairy cell leukemia (HCL). However, little is known about long-term outcomes and response to retreatment. Herein, we report the results of 36 patients with R/R HCL treated with vemurafenib from the United States arm of the phase 2 clinical trial (NCT01711632). The best overall response rate was 86%, including 33% complete response (CR) and 53% partial response (PR). After a median follow-up of 40 months, 21 of 31 responders (68%) experienced relapse with a median relapse-free survival (RFS) of 19 months (range, 12.5-53.9 months). There was no significant difference in the RFS for patients with CR vs PR. Fourteen of 21 (67%) relapsed patients were retreated with vemurafenib, with 86% achieving complete hematologic response. Two patients acquired resistance to vemurafenib with the emergence of new KRAS and CDKN2A mutations, respectively. Six of 12 (50%) responders to vemurafenib retreatment experienced another relapse with a median RFS of 12.7 months. Overall survival (OS) was 82% at 4 years, with a significantly shorter OS in patients who relapsed within 1 year of initial treatment with vemurafenib. Higher cumulative doses or a longer duration of treatment did not lengthen the durability of response. All adverse events in the retreatment cohort were grade 1/2 except for 1 case of a grade 3 rash and 1 grade 3 fever/pneumonia. Our data suggest that vemurafenib retreatment is a safe and effective option for patients with R/R HCL.

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Long-term outcomes in patients with relapsed or refractory hairy cell leukemia treated with vemurafenib monotherapy

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