Autologous stem cell transplantation after anti-PD-1 therapy for multiply relapsed or refractory Hodgkin lymphoma

Autologous stem cell transplantation (ASCT) can be curative for patients with relapsed/refractory Hodgkin lymphoma (HL). Based on studies suggesting that anti-PD-1 monoclonal antibodies (mAbs) can sensitize patients to subsequent chemotherapy, we hypothesized that anti-PD-1 therapy before ASCT would...

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Veröffentlicht in:Blood advances 2021-03, Vol.5 (6), p.1648-1659
Hauptverfasser: Merryman, Reid W., Redd, Robert A., Nishihori, Taiga, Chavez, Julio, Nieto, Yago, Darrah, Justin M., Rao, Uttam, Byrne, Michael T., Bond, David A., Maddocks, Kami J., Spinner, Michael A., Advani, Ranjana H., Ballard, Hatcher J., Svoboda, Jakub, Singh, Anurag K., McGuirk, Joseph P., Modi, Dipenkumar, Ramchandren, Radhakrishnan, Romancik, Jason, Cohen, Jonathon B., Frigault, Matthew J., Chen, Yi-Bin, Serritella, Anthony V., Kline, Justine, Ansell, Stephen, Nathan, Sunita, Rahimian, Maryam, Joyce, Robin M., Shah, Mansi, David, Kevin A., Park, Steven, Beaven, Anne W., Habib, Alma, Bachanova, Veronika, Nakhoda, Shazia, Khan, Nadia, Lynch, Ryan C., Smith, Stephen D., Ho, Vincent T., LaCasce, Ann, Armand, Philippe, Herrera, Alex F.
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container_end_page 1659
container_issue 6
container_start_page 1648
container_title Blood advances
container_volume 5
creator Merryman, Reid W.
Redd, Robert A.
Nishihori, Taiga
Chavez, Julio
Nieto, Yago
Darrah, Justin M.
Rao, Uttam
Byrne, Michael T.
Bond, David A.
Maddocks, Kami J.
Spinner, Michael A.
Advani, Ranjana H.
Ballard, Hatcher J.
Svoboda, Jakub
Singh, Anurag K.
McGuirk, Joseph P.
Modi, Dipenkumar
Ramchandren, Radhakrishnan
Romancik, Jason
Cohen, Jonathon B.
Frigault, Matthew J.
Chen, Yi-Bin
Serritella, Anthony V.
Kline, Justine
Ansell, Stephen
Nathan, Sunita
Rahimian, Maryam
Joyce, Robin M.
Shah, Mansi
David, Kevin A.
Park, Steven
Beaven, Anne W.
Habib, Alma
Bachanova, Veronika
Nakhoda, Shazia
Khan, Nadia
Lynch, Ryan C.
Smith, Stephen D.
Ho, Vincent T.
LaCasce, Ann
Armand, Philippe
Herrera, Alex F.
description Autologous stem cell transplantation (ASCT) can be curative for patients with relapsed/refractory Hodgkin lymphoma (HL). Based on studies suggesting that anti-PD-1 monoclonal antibodies (mAbs) can sensitize patients to subsequent chemotherapy, we hypothesized that anti-PD-1 therapy before ASCT would result in acceptable outcomes among high-risk patients who progressed on or responded insufficiently to ≥1 salvage regimen, including chemorefractory patients who are traditionally considered poor ASCT candidates. We retrospectively identified 78 HL patients who underwent ASCT after receiving an anti-PD-1 mAb (alone or in combination) as third-line or later therapy across 22 centers. Chemorefractory disease was common, including 42 patients (54%) refractory to ≥2 consecutive systemic therapies immediately before anti-PD-1 treatment. Fifty-eight (74%) patients underwent ASCT after anti-PD-1 treatment, while 20 patients (26%) received additional therapy after PD-1 blockade and before ASCT. Patients received a median of 4 systemic therapies (range, 3-7) before ASCT, and 31 patients (41%) had a positive pre-ASCT positron emission tomography (PET) result. After a median post-ASCT follow-up of 19.6 months, the 18-month progression-free survival (PFS) and overall survival were 81% (95% CI, 69-89) and 96% (95% confidence interval [CI], 87-99), respectively. Favorable outcomes were observed for patients who were refractory to 2 consecutive therapies immediately before PD-1 blockade (18-month PFS, 78%), had a positive pre-ASCT PET (18-month PFS, 75%), or received ≥4 systemic therapies before ASCT (18-month PFS, 73%), while PD-1 nonresponders had inferior outcomes (18-month PFS, 51%). In this high-risk cohort, ASCT after anti-PD-1 therapy was associated with excellent outcomes, even among heavily pretreated, previously chemorefractory patients. •ASCT after PD-1-blockade resulted in very favorable outcomes among high-risk patients with multiply relapsed/refractory HL.•Response to PD-1 blockade, and not prior chemosensitivity, best predicted post-ASCT PFS in this cohort. [Display omitted]
doi_str_mv 10.1182/bloodadvances.2020003556
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Based on studies suggesting that anti-PD-1 monoclonal antibodies (mAbs) can sensitize patients to subsequent chemotherapy, we hypothesized that anti-PD-1 therapy before ASCT would result in acceptable outcomes among high-risk patients who progressed on or responded insufficiently to ≥1 salvage regimen, including chemorefractory patients who are traditionally considered poor ASCT candidates. We retrospectively identified 78 HL patients who underwent ASCT after receiving an anti-PD-1 mAb (alone or in combination) as third-line or later therapy across 22 centers. Chemorefractory disease was common, including 42 patients (54%) refractory to ≥2 consecutive systemic therapies immediately before anti-PD-1 treatment. Fifty-eight (74%) patients underwent ASCT after anti-PD-1 treatment, while 20 patients (26%) received additional therapy after PD-1 blockade and before ASCT. Patients received a median of 4 systemic therapies (range, 3-7) before ASCT, and 31 patients (41%) had a positive pre-ASCT positron emission tomography (PET) result. After a median post-ASCT follow-up of 19.6 months, the 18-month progression-free survival (PFS) and overall survival were 81% (95% CI, 69-89) and 96% (95% confidence interval [CI], 87-99), respectively. Favorable outcomes were observed for patients who were refractory to 2 consecutive therapies immediately before PD-1 blockade (18-month PFS, 78%), had a positive pre-ASCT PET (18-month PFS, 75%), or received ≥4 systemic therapies before ASCT (18-month PFS, 73%), while PD-1 nonresponders had inferior outcomes (18-month PFS, 51%). In this high-risk cohort, ASCT after anti-PD-1 therapy was associated with excellent outcomes, even among heavily pretreated, previously chemorefractory patients. •ASCT after PD-1-blockade resulted in very favorable outcomes among high-risk patients with multiply relapsed/refractory HL.•Response to PD-1 blockade, and not prior chemosensitivity, best predicted post-ASCT PFS in this cohort. 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Based on studies suggesting that anti-PD-1 monoclonal antibodies (mAbs) can sensitize patients to subsequent chemotherapy, we hypothesized that anti-PD-1 therapy before ASCT would result in acceptable outcomes among high-risk patients who progressed on or responded insufficiently to ≥1 salvage regimen, including chemorefractory patients who are traditionally considered poor ASCT candidates. We retrospectively identified 78 HL patients who underwent ASCT after receiving an anti-PD-1 mAb (alone or in combination) as third-line or later therapy across 22 centers. Chemorefractory disease was common, including 42 patients (54%) refractory to ≥2 consecutive systemic therapies immediately before anti-PD-1 treatment. Fifty-eight (74%) patients underwent ASCT after anti-PD-1 treatment, while 20 patients (26%) received additional therapy after PD-1 blockade and before ASCT. Patients received a median of 4 systemic therapies (range, 3-7) before ASCT, and 31 patients (41%) had a positive pre-ASCT positron emission tomography (PET) result. After a median post-ASCT follow-up of 19.6 months, the 18-month progression-free survival (PFS) and overall survival were 81% (95% CI, 69-89) and 96% (95% confidence interval [CI], 87-99), respectively. Favorable outcomes were observed for patients who were refractory to 2 consecutive therapies immediately before PD-1 blockade (18-month PFS, 78%), had a positive pre-ASCT PET (18-month PFS, 75%), or received ≥4 systemic therapies before ASCT (18-month PFS, 73%), while PD-1 nonresponders had inferior outcomes (18-month PFS, 51%). In this high-risk cohort, ASCT after anti-PD-1 therapy was associated with excellent outcomes, even among heavily pretreated, previously chemorefractory patients. •ASCT after PD-1-blockade resulted in very favorable outcomes among high-risk patients with multiply relapsed/refractory HL.•Response to PD-1 blockade, and not prior chemosensitivity, best predicted post-ASCT PFS in this cohort. 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Alma</creatorcontrib><creatorcontrib>Bachanova, Veronika</creatorcontrib><creatorcontrib>Nakhoda, Shazia</creatorcontrib><creatorcontrib>Khan, Nadia</creatorcontrib><creatorcontrib>Lynch, Ryan C.</creatorcontrib><creatorcontrib>Smith, Stephen D.</creatorcontrib><creatorcontrib>Ho, Vincent T.</creatorcontrib><creatorcontrib>LaCasce, Ann</creatorcontrib><creatorcontrib>Armand, Philippe</creatorcontrib><creatorcontrib>Herrera, Alex F.</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Blood advances</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Merryman, Reid W.</au><au>Redd, Robert A.</au><au>Nishihori, Taiga</au><au>Chavez, Julio</au><au>Nieto, Yago</au><au>Darrah, Justin M.</au><au>Rao, Uttam</au><au>Byrne, Michael T.</au><au>Bond, David A.</au><au>Maddocks, Kami J.</au><au>Spinner, Michael A.</au><au>Advani, Ranjana H.</au><au>Ballard, Hatcher J.</au><au>Svoboda, Jakub</au><au>Singh, Anurag K.</au><au>McGuirk, Joseph P.</au><au>Modi, Dipenkumar</au><au>Ramchandren, Radhakrishnan</au><au>Romancik, Jason</au><au>Cohen, Jonathon B.</au><au>Frigault, Matthew J.</au><au>Chen, Yi-Bin</au><au>Serritella, Anthony V.</au><au>Kline, Justine</au><au>Ansell, Stephen</au><au>Nathan, Sunita</au><au>Rahimian, Maryam</au><au>Joyce, Robin M.</au><au>Shah, Mansi</au><au>David, Kevin A.</au><au>Park, Steven</au><au>Beaven, Anne W.</au><au>Habib, Alma</au><au>Bachanova, Veronika</au><au>Nakhoda, Shazia</au><au>Khan, Nadia</au><au>Lynch, Ryan C.</au><au>Smith, Stephen D.</au><au>Ho, Vincent T.</au><au>LaCasce, Ann</au><au>Armand, Philippe</au><au>Herrera, Alex F.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Autologous stem cell transplantation after anti-PD-1 therapy for multiply relapsed or refractory Hodgkin lymphoma</atitle><jtitle>Blood advances</jtitle><addtitle>Blood Adv</addtitle><date>2021-03-23</date><risdate>2021</risdate><volume>5</volume><issue>6</issue><spage>1648</spage><epage>1659</epage><pages>1648-1659</pages><issn>2473-9529</issn><eissn>2473-9537</eissn><abstract>Autologous stem cell transplantation (ASCT) can be curative for patients with relapsed/refractory Hodgkin lymphoma (HL). Based on studies suggesting that anti-PD-1 monoclonal antibodies (mAbs) can sensitize patients to subsequent chemotherapy, we hypothesized that anti-PD-1 therapy before ASCT would result in acceptable outcomes among high-risk patients who progressed on or responded insufficiently to ≥1 salvage regimen, including chemorefractory patients who are traditionally considered poor ASCT candidates. We retrospectively identified 78 HL patients who underwent ASCT after receiving an anti-PD-1 mAb (alone or in combination) as third-line or later therapy across 22 centers. Chemorefractory disease was common, including 42 patients (54%) refractory to ≥2 consecutive systemic therapies immediately before anti-PD-1 treatment. Fifty-eight (74%) patients underwent ASCT after anti-PD-1 treatment, while 20 patients (26%) received additional therapy after PD-1 blockade and before ASCT. Patients received a median of 4 systemic therapies (range, 3-7) before ASCT, and 31 patients (41%) had a positive pre-ASCT positron emission tomography (PET) result. After a median post-ASCT follow-up of 19.6 months, the 18-month progression-free survival (PFS) and overall survival were 81% (95% CI, 69-89) and 96% (95% confidence interval [CI], 87-99), respectively. Favorable outcomes were observed for patients who were refractory to 2 consecutive therapies immediately before PD-1 blockade (18-month PFS, 78%), had a positive pre-ASCT PET (18-month PFS, 75%), or received ≥4 systemic therapies before ASCT (18-month PFS, 73%), while PD-1 nonresponders had inferior outcomes (18-month PFS, 51%). In this high-risk cohort, ASCT after anti-PD-1 therapy was associated with excellent outcomes, even among heavily pretreated, previously chemorefractory patients. •ASCT after PD-1-blockade resulted in very favorable outcomes among high-risk patients with multiply relapsed/refractory HL.•Response to PD-1 blockade, and not prior chemosensitivity, best predicted post-ASCT PFS in this cohort. [Display omitted]</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>33710337</pmid><doi>10.1182/bloodadvances.2020003556</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0001-7349-0176</orcidid><orcidid>https://orcid.org/0000-0002-7251-8082</orcidid><orcidid>https://orcid.org/0000-0001-6034-8939</orcidid><orcidid>https://orcid.org/0000-0002-1329-5288</orcidid><orcidid>https://orcid.org/0000-0001-5354-7593</orcidid><orcidid>https://orcid.org/0000-0002-2723-6481</orcidid><orcidid>https://orcid.org/0000-0002-0539-4796</orcidid><orcidid>https://orcid.org/0000-0001-5674-6408</orcidid><orcidid>https://orcid.org/0000-0003-0773-1829</orcidid><orcidid>https://orcid.org/0000-0001-6525-8844</orcidid><orcidid>https://orcid.org/0000-0001-6703-0894</orcidid><orcidid>https://orcid.org/0000-0003-0054-9362</orcidid><orcidid>https://orcid.org/0000-0001-8884-3085</orcidid><orcidid>https://orcid.org/0000-0002-2621-7924</orcidid><oa>free_for_read</oa></addata></record>
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subjects Lymphoid Neoplasia
title Autologous stem cell transplantation after anti-PD-1 therapy for multiply relapsed or refractory Hodgkin lymphoma
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