Post-Allograft Romidepsin Maintenance Mitigates Relapse Risk and Stimulates the Graft-Versus-Malignancy Effect through Enhanced NK-Cell Cytotoxicity in Patients with T-Cell Malignancies: Final Results of a Phase I/II Trial
Background: For patients with high risk, and relapsed/refractory T-cell malignancies allogeneic stem cell transplant (allo-SCT) is the only available potentially curative therapy. The efficacy of allo-SCT is limited in this population by high rates of relapse, with rates up to 55-60% post-allo-SCT....
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| Veröffentlicht in: | Blood 2023-11, Vol.142 (Supplement 1), p.184-184 |
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| creator | Hosing, Chitra Braunstein, Zachary McLaughlin, Eric Valdez, Benigno C. Andersson, Borje S. Popat, Uday R. Vasu, Sumithira Bezzera, Evandro Sanchez-Petitto, Gabriela Wall, Sarah A Jaglowski, Samantha M. Penza, Sam Choe, Hannah Wei, Lai Nakkula, Robin Cash, Alex Champlin, Richard E. de Lima, Marcos Devine, Steven M. Lee, Dean Anthony Brammer, Jonathan E. |
| description | Background: For patients with high risk, and relapsed/refractory T-cell malignancies allogeneic stem cell transplant (allo-SCT) is the only available potentially curative therapy. The efficacy of allo-SCT is limited in this population by high rates of relapse, with rates up to 55-60% post-allo-SCT. We designed a phase I/II trial, evaluating the combination of the histone deacetylases inhibitor romidepsin (rom) with busulfan/fludarabine (BuFlu) conditioning, followed by romidepsin maintenance (m-rom) in patients receiving allo-SCT for T-cell malignancies (NCT02512497). Here we present final clinical results of this therapeutic approach, including an evaluation of the stimulatory effects of m-rom on the graft-versus-malignancy effect through NK-cells post-allo-SCT.
Methods:
This was a phase I/II clinical trial. Eligible patients had: a diagnosis of T-cell leukemia (including T-acute lymphoblastic leukemia) or T-cell lymphoma (TCL, cutaneous or peripheral) in at least a partial remission requiring an allo-SCT, |
| doi_str_mv | 10.1182/blood-2023-190213 |
| format | Article |
| fullrecord | <record><control><sourceid>crossref</sourceid><recordid>TN_cdi_crossref_primary_10_1182_blood_2023_190213</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>10_1182_blood_2023_190213</sourcerecordid><originalsourceid>FETCH-LOGICAL-c853-a3e10a3968070be1e465d994c1f4522dac5c6930f347311588bb243e7baaa13c3</originalsourceid><addsrcrecordid>eNo9kU1u2zAQhYmgAeqmOUB3cwHW_JFsKbvAcFyjcWo4RrbCiBpZbGnREGk0umzOUikusprFPHzvAR9j36T4LmWmpqXzvuJKKM1lLpTUV2wiU5VxIZT4xCZCiBlP8rn8zL6E8FsImWiVTtjb1ofI753zhw7rCDt_tBWdgm1hg7aN1GJrCDY22gNGCrAjh6dAsLPhD2BbwXO0x7N7_8WGYDVi-At14Rz4Bp09jIQelnVNJg6Rzp8PDSzbZgRX8PSTL8g5WPTRR_9qjY09DO1bjJbaGOCvjQ3sL6EPnqVwBw-2RTcMCmc35HwNCNsGh23r6XoN-86i-8qua3SBbv_fG7Z_WO4XP_jjr9V6cf_ITZZqjpqkQJ3PMjEXJUlKZmmV54mRdZIqVaFJzSzXotbJXEuZZllZqkTTvEREqY2-YfKCNZ0PoaO6OHX2iF1fSFGMfop3P8Xop7j40f8ALHWIUw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Post-Allograft Romidepsin Maintenance Mitigates Relapse Risk and Stimulates the Graft-Versus-Malignancy Effect through Enhanced NK-Cell Cytotoxicity in Patients with T-Cell Malignancies: Final Results of a Phase I/II Trial</title><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><creator>Hosing, Chitra ; Braunstein, Zachary ; McLaughlin, Eric ; Valdez, Benigno C. ; Andersson, Borje S. ; Popat, Uday R. ; Vasu, Sumithira ; Bezzera, Evandro ; Sanchez-Petitto, Gabriela ; Wall, Sarah A ; Jaglowski, Samantha M. ; Penza, Sam ; Choe, Hannah ; Wei, Lai ; Nakkula, Robin ; Cash, Alex ; Champlin, Richard E. ; de Lima, Marcos ; Devine, Steven M. ; Lee, Dean Anthony ; Brammer, Jonathan E.</creator><creatorcontrib>Hosing, Chitra ; Braunstein, Zachary ; McLaughlin, Eric ; Valdez, Benigno C. ; Andersson, Borje S. ; Popat, Uday R. ; Vasu, Sumithira ; Bezzera, Evandro ; Sanchez-Petitto, Gabriela ; Wall, Sarah A ; Jaglowski, Samantha M. ; Penza, Sam ; Choe, Hannah ; Wei, Lai ; Nakkula, Robin ; Cash, Alex ; Champlin, Richard E. ; de Lima, Marcos ; Devine, Steven M. ; Lee, Dean Anthony ; Brammer, Jonathan E.</creatorcontrib><description>Background: For patients with high risk, and relapsed/refractory T-cell malignancies allogeneic stem cell transplant (allo-SCT) is the only available potentially curative therapy. The efficacy of allo-SCT is limited in this population by high rates of relapse, with rates up to 55-60% post-allo-SCT. We designed a phase I/II trial, evaluating the combination of the histone deacetylases inhibitor romidepsin (rom) with busulfan/fludarabine (BuFlu) conditioning, followed by romidepsin maintenance (m-rom) in patients receiving allo-SCT for T-cell malignancies (NCT02512497). Here we present final clinical results of this therapeutic approach, including an evaluation of the stimulatory effects of m-rom on the graft-versus-malignancy effect through NK-cells post-allo-SCT.
Methods:
This was a phase I/II clinical trial. Eligible patients had: a diagnosis of T-cell leukemia (including T-acute lymphoblastic leukemia) or T-cell lymphoma (TCL, cutaneous or peripheral) in at least a partial remission requiring an allo-SCT, <70 years of age, with a matched sibling/unrelated donor. Patients received myeloablative (20K) or reduced intensity (16K) BuFlu with rom, followed by standard tacrolimus/methotrexate GVHD prophylaxis and anti-thymocyte globulin for unrelated donors (MUD). An expansion cohort of up to 30 patients (total) was included. M-rom was initiated between day +28 and +100 for 1 year (2 nd year optional), with built in dose reductions for toxicity. An efficacy endpoint of 20% reduction in relapse risk at 1-year in the whole cohort or any individual disease cohort was set based upon historical/CIBMTR (Center for Blood and Marrow Transplant Research) controls was pre-specified. The effect of m-rom on NK-cell cytotoxicity was assessed on samples taken pre-transplant, and 1, 3, 6, 12 months post allo-SCT. NK cytotoxicity was assessed by isolating mononuclear cells from patient samples at each timepoint, comparing those on m-rom (n=13) versus those who did BuFlu controls who did not receive m-rom (n=16). Cells were targeted against K562 targets using the calcein-AM assay. K-M and Fine-Gray models were used to estimate PFS, OS, and cumulative incidence, and compare survival across groups.
Results:
28 patients were enrolled on this trial (Table). With a median follow-up time of 15 months, the median OS is 3.3 years (95% CI: 0.85-not reached), with a 1 and 3 year OS probability of 68% and 54%. The median PFS is 2.3 years (95% CI: 0.6-not reached), with 1 and 3-year PFS of 61% and 41%. Cumulative incidence (CI) of NRM at day 100 and 1 year were 14.3% and 21.4%. CI of grade II-IV aGHVD and extensive cGVHD were 46.4% and 38%. The CI of relapse (CIR) was 18.1% at 1 year and 33% at 3 -years. There was no difference between PFS among patients with MRD versus those without MRD prior to transplant (p=0.43).
The CIR of patients with TCL was 9.3% at 1 and 3 years, whereas the CIR of patients with leukemia was 25% at 1 year and 48% at 3 years. No patients with PTCL relapsed, 1/2 patients with CTCL relapsed, and 4/6 patients with T-PLL are alive, disease free. Pre-specified general CIR was 55% for all patients. With an overall CIR of 18% at 1 year, and 33% at 3-years, this trial met its pre-specified endpoint of decreasing relapse by 20% at 1-year, and performed well compared to published CIBMTR control populations. Matched propensity score analysis across disease subsets with CIBMTR controls will be presented.
18/28 (64%) of patients received m-rom with a median number of 13 cycles (range 1-47). 8 patients experienced grade 3/4 adverse events (AE), and 1 patient discontinued m-rom due to toxicity, unlikely related to romidepsin (loss of CD3 chimerism). When NK-cytotoxicity was assessed between the two groups after starting maintenance, NK-cytotoxicity in the m-rom group was significantly higher than in those without m-rom (p<0.0001) (Figure).
Conclusions:
BuFluRom with m-rom is effective at decreasing relapse in patients with T-cell malignancies, with 1-year CI relapse below expected relapse rates for this set of diseases, meeting the pre-specified efficacy endpoint. NK-cell cytotoxicity data in a large sample set of trial patients demonstrates that m-rom enhances NK-cell cytotoxicity post allo-SCT, augmenting the GVL effect and likely accounting for at a minimum, some of the decrease in relapse seen on this trial. M-rom should be considered a new option post allo-SCT to mitigate relapse in patients with T-cell malignancies.</description><identifier>ISSN: 0006-4971</identifier><identifier>EISSN: 1528-0020</identifier><identifier>DOI: 10.1182/blood-2023-190213</identifier><language>eng</language><ispartof>Blood, 2023-11, Vol.142 (Supplement 1), p.184-184</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids></links><search><creatorcontrib>Hosing, Chitra</creatorcontrib><creatorcontrib>Braunstein, Zachary</creatorcontrib><creatorcontrib>McLaughlin, Eric</creatorcontrib><creatorcontrib>Valdez, Benigno C.</creatorcontrib><creatorcontrib>Andersson, Borje S.</creatorcontrib><creatorcontrib>Popat, Uday R.</creatorcontrib><creatorcontrib>Vasu, Sumithira</creatorcontrib><creatorcontrib>Bezzera, Evandro</creatorcontrib><creatorcontrib>Sanchez-Petitto, Gabriela</creatorcontrib><creatorcontrib>Wall, Sarah A</creatorcontrib><creatorcontrib>Jaglowski, Samantha M.</creatorcontrib><creatorcontrib>Penza, Sam</creatorcontrib><creatorcontrib>Choe, Hannah</creatorcontrib><creatorcontrib>Wei, Lai</creatorcontrib><creatorcontrib>Nakkula, Robin</creatorcontrib><creatorcontrib>Cash, Alex</creatorcontrib><creatorcontrib>Champlin, Richard E.</creatorcontrib><creatorcontrib>de Lima, Marcos</creatorcontrib><creatorcontrib>Devine, Steven M.</creatorcontrib><creatorcontrib>Lee, Dean Anthony</creatorcontrib><creatorcontrib>Brammer, Jonathan E.</creatorcontrib><title>Post-Allograft Romidepsin Maintenance Mitigates Relapse Risk and Stimulates the Graft-Versus-Malignancy Effect through Enhanced NK-Cell Cytotoxicity in Patients with T-Cell Malignancies: Final Results of a Phase I/II Trial</title><title>Blood</title><description>Background: For patients with high risk, and relapsed/refractory T-cell malignancies allogeneic stem cell transplant (allo-SCT) is the only available potentially curative therapy. The efficacy of allo-SCT is limited in this population by high rates of relapse, with rates up to 55-60% post-allo-SCT. We designed a phase I/II trial, evaluating the combination of the histone deacetylases inhibitor romidepsin (rom) with busulfan/fludarabine (BuFlu) conditioning, followed by romidepsin maintenance (m-rom) in patients receiving allo-SCT for T-cell malignancies (NCT02512497). Here we present final clinical results of this therapeutic approach, including an evaluation of the stimulatory effects of m-rom on the graft-versus-malignancy effect through NK-cells post-allo-SCT.
Methods:
This was a phase I/II clinical trial. Eligible patients had: a diagnosis of T-cell leukemia (including T-acute lymphoblastic leukemia) or T-cell lymphoma (TCL, cutaneous or peripheral) in at least a partial remission requiring an allo-SCT, <70 years of age, with a matched sibling/unrelated donor. Patients received myeloablative (20K) or reduced intensity (16K) BuFlu with rom, followed by standard tacrolimus/methotrexate GVHD prophylaxis and anti-thymocyte globulin for unrelated donors (MUD). An expansion cohort of up to 30 patients (total) was included. M-rom was initiated between day +28 and +100 for 1 year (2 nd year optional), with built in dose reductions for toxicity. An efficacy endpoint of 20% reduction in relapse risk at 1-year in the whole cohort or any individual disease cohort was set based upon historical/CIBMTR (Center for Blood and Marrow Transplant Research) controls was pre-specified. The effect of m-rom on NK-cell cytotoxicity was assessed on samples taken pre-transplant, and 1, 3, 6, 12 months post allo-SCT. NK cytotoxicity was assessed by isolating mononuclear cells from patient samples at each timepoint, comparing those on m-rom (n=13) versus those who did BuFlu controls who did not receive m-rom (n=16). Cells were targeted against K562 targets using the calcein-AM assay. K-M and Fine-Gray models were used to estimate PFS, OS, and cumulative incidence, and compare survival across groups.
Results:
28 patients were enrolled on this trial (Table). With a median follow-up time of 15 months, the median OS is 3.3 years (95% CI: 0.85-not reached), with a 1 and 3 year OS probability of 68% and 54%. The median PFS is 2.3 years (95% CI: 0.6-not reached), with 1 and 3-year PFS of 61% and 41%. Cumulative incidence (CI) of NRM at day 100 and 1 year were 14.3% and 21.4%. CI of grade II-IV aGHVD and extensive cGVHD were 46.4% and 38%. The CI of relapse (CIR) was 18.1% at 1 year and 33% at 3 -years. There was no difference between PFS among patients with MRD versus those without MRD prior to transplant (p=0.43).
The CIR of patients with TCL was 9.3% at 1 and 3 years, whereas the CIR of patients with leukemia was 25% at 1 year and 48% at 3 years. No patients with PTCL relapsed, 1/2 patients with CTCL relapsed, and 4/6 patients with T-PLL are alive, disease free. Pre-specified general CIR was 55% for all patients. With an overall CIR of 18% at 1 year, and 33% at 3-years, this trial met its pre-specified endpoint of decreasing relapse by 20% at 1-year, and performed well compared to published CIBMTR control populations. Matched propensity score analysis across disease subsets with CIBMTR controls will be presented.
18/28 (64%) of patients received m-rom with a median number of 13 cycles (range 1-47). 8 patients experienced grade 3/4 adverse events (AE), and 1 patient discontinued m-rom due to toxicity, unlikely related to romidepsin (loss of CD3 chimerism). When NK-cytotoxicity was assessed between the two groups after starting maintenance, NK-cytotoxicity in the m-rom group was significantly higher than in those without m-rom (p<0.0001) (Figure).
Conclusions:
BuFluRom with m-rom is effective at decreasing relapse in patients with T-cell malignancies, with 1-year CI relapse below expected relapse rates for this set of diseases, meeting the pre-specified efficacy endpoint. NK-cell cytotoxicity data in a large sample set of trial patients demonstrates that m-rom enhances NK-cell cytotoxicity post allo-SCT, augmenting the GVL effect and likely accounting for at a minimum, some of the decrease in relapse seen on this trial. M-rom should be considered a new option post allo-SCT to mitigate relapse in patients with T-cell malignancies.</description><issn>0006-4971</issn><issn>1528-0020</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><recordid>eNo9kU1u2zAQhYmgAeqmOUB3cwHW_JFsKbvAcFyjcWo4RrbCiBpZbGnREGk0umzOUikusprFPHzvAR9j36T4LmWmpqXzvuJKKM1lLpTUV2wiU5VxIZT4xCZCiBlP8rn8zL6E8FsImWiVTtjb1ofI753zhw7rCDt_tBWdgm1hg7aN1GJrCDY22gNGCrAjh6dAsLPhD2BbwXO0x7N7_8WGYDVi-At14Rz4Bp09jIQelnVNJg6Rzp8PDSzbZgRX8PSTL8g5WPTRR_9qjY09DO1bjJbaGOCvjQ3sL6EPnqVwBw-2RTcMCmc35HwNCNsGh23r6XoN-86i-8qua3SBbv_fG7Z_WO4XP_jjr9V6cf_ITZZqjpqkQJ3PMjEXJUlKZmmV54mRdZIqVaFJzSzXotbJXEuZZllZqkTTvEREqY2-YfKCNZ0PoaO6OHX2iF1fSFGMfop3P8Xop7j40f8ALHWIUw</recordid><startdate>20231102</startdate><enddate>20231102</enddate><creator>Hosing, Chitra</creator><creator>Braunstein, Zachary</creator><creator>McLaughlin, Eric</creator><creator>Valdez, Benigno C.</creator><creator>Andersson, Borje S.</creator><creator>Popat, Uday R.</creator><creator>Vasu, Sumithira</creator><creator>Bezzera, Evandro</creator><creator>Sanchez-Petitto, Gabriela</creator><creator>Wall, Sarah A</creator><creator>Jaglowski, Samantha M.</creator><creator>Penza, Sam</creator><creator>Choe, Hannah</creator><creator>Wei, Lai</creator><creator>Nakkula, Robin</creator><creator>Cash, Alex</creator><creator>Champlin, Richard E.</creator><creator>de Lima, Marcos</creator><creator>Devine, Steven M.</creator><creator>Lee, Dean Anthony</creator><creator>Brammer, Jonathan E.</creator><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>20231102</creationdate><title>Post-Allograft Romidepsin Maintenance Mitigates Relapse Risk and Stimulates the Graft-Versus-Malignancy Effect through Enhanced NK-Cell Cytotoxicity in Patients with T-Cell Malignancies: Final Results of a Phase I/II Trial</title><author>Hosing, Chitra ; Braunstein, Zachary ; McLaughlin, Eric ; Valdez, Benigno C. ; Andersson, Borje S. ; Popat, Uday R. ; Vasu, Sumithira ; Bezzera, Evandro ; Sanchez-Petitto, Gabriela ; Wall, Sarah A ; Jaglowski, Samantha M. ; Penza, Sam ; Choe, Hannah ; Wei, Lai ; Nakkula, Robin ; Cash, Alex ; Champlin, Richard E. ; de Lima, Marcos ; Devine, Steven M. ; Lee, Dean Anthony ; Brammer, Jonathan E.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c853-a3e10a3968070be1e465d994c1f4522dac5c6930f347311588bb243e7baaa13c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hosing, Chitra</creatorcontrib><creatorcontrib>Braunstein, Zachary</creatorcontrib><creatorcontrib>McLaughlin, Eric</creatorcontrib><creatorcontrib>Valdez, Benigno C.</creatorcontrib><creatorcontrib>Andersson, Borje S.</creatorcontrib><creatorcontrib>Popat, Uday R.</creatorcontrib><creatorcontrib>Vasu, Sumithira</creatorcontrib><creatorcontrib>Bezzera, Evandro</creatorcontrib><creatorcontrib>Sanchez-Petitto, Gabriela</creatorcontrib><creatorcontrib>Wall, Sarah A</creatorcontrib><creatorcontrib>Jaglowski, Samantha M.</creatorcontrib><creatorcontrib>Penza, Sam</creatorcontrib><creatorcontrib>Choe, Hannah</creatorcontrib><creatorcontrib>Wei, Lai</creatorcontrib><creatorcontrib>Nakkula, Robin</creatorcontrib><creatorcontrib>Cash, Alex</creatorcontrib><creatorcontrib>Champlin, Richard E.</creatorcontrib><creatorcontrib>de Lima, Marcos</creatorcontrib><creatorcontrib>Devine, Steven M.</creatorcontrib><creatorcontrib>Lee, Dean Anthony</creatorcontrib><creatorcontrib>Brammer, Jonathan E.</creatorcontrib><collection>CrossRef</collection><jtitle>Blood</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hosing, Chitra</au><au>Braunstein, Zachary</au><au>McLaughlin, Eric</au><au>Valdez, Benigno C.</au><au>Andersson, Borje S.</au><au>Popat, Uday R.</au><au>Vasu, Sumithira</au><au>Bezzera, Evandro</au><au>Sanchez-Petitto, Gabriela</au><au>Wall, Sarah A</au><au>Jaglowski, Samantha M.</au><au>Penza, Sam</au><au>Choe, Hannah</au><au>Wei, Lai</au><au>Nakkula, Robin</au><au>Cash, Alex</au><au>Champlin, Richard E.</au><au>de Lima, Marcos</au><au>Devine, Steven M.</au><au>Lee, Dean Anthony</au><au>Brammer, Jonathan E.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Post-Allograft Romidepsin Maintenance Mitigates Relapse Risk and Stimulates the Graft-Versus-Malignancy Effect through Enhanced NK-Cell Cytotoxicity in Patients with T-Cell Malignancies: Final Results of a Phase I/II Trial</atitle><jtitle>Blood</jtitle><date>2023-11-02</date><risdate>2023</risdate><volume>142</volume><issue>Supplement 1</issue><spage>184</spage><epage>184</epage><pages>184-184</pages><issn>0006-4971</issn><eissn>1528-0020</eissn><abstract>Background: For patients with high risk, and relapsed/refractory T-cell malignancies allogeneic stem cell transplant (allo-SCT) is the only available potentially curative therapy. The efficacy of allo-SCT is limited in this population by high rates of relapse, with rates up to 55-60% post-allo-SCT. We designed a phase I/II trial, evaluating the combination of the histone deacetylases inhibitor romidepsin (rom) with busulfan/fludarabine (BuFlu) conditioning, followed by romidepsin maintenance (m-rom) in patients receiving allo-SCT for T-cell malignancies (NCT02512497). Here we present final clinical results of this therapeutic approach, including an evaluation of the stimulatory effects of m-rom on the graft-versus-malignancy effect through NK-cells post-allo-SCT.
Methods:
This was a phase I/II clinical trial. Eligible patients had: a diagnosis of T-cell leukemia (including T-acute lymphoblastic leukemia) or T-cell lymphoma (TCL, cutaneous or peripheral) in at least a partial remission requiring an allo-SCT, <70 years of age, with a matched sibling/unrelated donor. Patients received myeloablative (20K) or reduced intensity (16K) BuFlu with rom, followed by standard tacrolimus/methotrexate GVHD prophylaxis and anti-thymocyte globulin for unrelated donors (MUD). An expansion cohort of up to 30 patients (total) was included. M-rom was initiated between day +28 and +100 for 1 year (2 nd year optional), with built in dose reductions for toxicity. An efficacy endpoint of 20% reduction in relapse risk at 1-year in the whole cohort or any individual disease cohort was set based upon historical/CIBMTR (Center for Blood and Marrow Transplant Research) controls was pre-specified. The effect of m-rom on NK-cell cytotoxicity was assessed on samples taken pre-transplant, and 1, 3, 6, 12 months post allo-SCT. NK cytotoxicity was assessed by isolating mononuclear cells from patient samples at each timepoint, comparing those on m-rom (n=13) versus those who did BuFlu controls who did not receive m-rom (n=16). Cells were targeted against K562 targets using the calcein-AM assay. K-M and Fine-Gray models were used to estimate PFS, OS, and cumulative incidence, and compare survival across groups.
Results:
28 patients were enrolled on this trial (Table). With a median follow-up time of 15 months, the median OS is 3.3 years (95% CI: 0.85-not reached), with a 1 and 3 year OS probability of 68% and 54%. The median PFS is 2.3 years (95% CI: 0.6-not reached), with 1 and 3-year PFS of 61% and 41%. Cumulative incidence (CI) of NRM at day 100 and 1 year were 14.3% and 21.4%. CI of grade II-IV aGHVD and extensive cGVHD were 46.4% and 38%. The CI of relapse (CIR) was 18.1% at 1 year and 33% at 3 -years. There was no difference between PFS among patients with MRD versus those without MRD prior to transplant (p=0.43).
The CIR of patients with TCL was 9.3% at 1 and 3 years, whereas the CIR of patients with leukemia was 25% at 1 year and 48% at 3 years. No patients with PTCL relapsed, 1/2 patients with CTCL relapsed, and 4/6 patients with T-PLL are alive, disease free. Pre-specified general CIR was 55% for all patients. With an overall CIR of 18% at 1 year, and 33% at 3-years, this trial met its pre-specified endpoint of decreasing relapse by 20% at 1-year, and performed well compared to published CIBMTR control populations. Matched propensity score analysis across disease subsets with CIBMTR controls will be presented.
18/28 (64%) of patients received m-rom with a median number of 13 cycles (range 1-47). 8 patients experienced grade 3/4 adverse events (AE), and 1 patient discontinued m-rom due to toxicity, unlikely related to romidepsin (loss of CD3 chimerism). When NK-cytotoxicity was assessed between the two groups after starting maintenance, NK-cytotoxicity in the m-rom group was significantly higher than in those without m-rom (p<0.0001) (Figure).
Conclusions:
BuFluRom with m-rom is effective at decreasing relapse in patients with T-cell malignancies, with 1-year CI relapse below expected relapse rates for this set of diseases, meeting the pre-specified efficacy endpoint. NK-cell cytotoxicity data in a large sample set of trial patients demonstrates that m-rom enhances NK-cell cytotoxicity post allo-SCT, augmenting the GVL effect and likely accounting for at a minimum, some of the decrease in relapse seen on this trial. M-rom should be considered a new option post allo-SCT to mitigate relapse in patients with T-cell malignancies.</abstract><doi>10.1182/blood-2023-190213</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0006-4971 |
| ispartof | Blood, 2023-11, Vol.142 (Supplement 1), p.184-184 |
| issn | 0006-4971 1528-0020 |
| language | eng |
| recordid | cdi_crossref_primary_10_1182_blood_2023_190213 |
| source | Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| title | Post-Allograft Romidepsin Maintenance Mitigates Relapse Risk and Stimulates the Graft-Versus-Malignancy Effect through Enhanced NK-Cell Cytotoxicity in Patients with T-Cell Malignancies: Final Results of a Phase I/II Trial |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-04T06%3A46%3A27IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-crossref&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Post-Allograft%20Romidepsin%20Maintenance%20Mitigates%20Relapse%20Risk%20and%20Stimulates%20the%20Graft-Versus-Malignancy%20Effect%20through%20Enhanced%20NK-Cell%20Cytotoxicity%20in%20Patients%20with%20T-Cell%20Malignancies:%20Final%20Results%20of%20a%20Phase%20I/II%20Trial&rft.jtitle=Blood&rft.au=Hosing,%20Chitra&rft.date=2023-11-02&rft.volume=142&rft.issue=Supplement%201&rft.spage=184&rft.epage=184&rft.pages=184-184&rft.issn=0006-4971&rft.eissn=1528-0020&rft_id=info:doi/10.1182/blood-2023-190213&rft_dat=%3Ccrossref%3E10_1182_blood_2023_190213%3C/crossref%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/&rfr_iscdi=true |