{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T17:59:17Z","timestamp":1790359157425,"version":"4.1.0"},"reference-count":0,"publisher":"American Society of Hematology","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"abstract":"<jats:p>In relapsed or refractory (R\/R) B-cell acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL), responses to the CD22 antibody-drug conjugate inotuzumab ozogamicin (INO) are frequent but short-lived. Based on preclinical evidence of synergy, we conducted a phase 1 trial of the BCL-2 inhibitor venetoclax (VEN) plus standard-dose INO for adults with R\/R CD22+ ALL\/LBL. Twenty-three patients enrolled (15 ALL, 8 LBL): three at dose level 1 (DL1; VEN 200 mg\/day), six at DL2 (VEN 400 mg\/day), and fourteen in an expansion cohort (VEN 400 mg\/day). The recommended dose was VEN 400 mg\/day for 21 days per cycle. No dose-limiting toxicities or early mortality occurred. Patients received a median of 2 cycles (range 1-5). The most common grade \u00b33 adverse events were thrombocytopenia (43.5%) and neutropenia (39.1%). Four patients (17.4%) developed sinusoidal obstructive syndrome. Of 22 evaluable patients, 21 (95.5%) achieved complete remission, including 19 after one cycle. Measurable residual disease (MRD) cleared in 16\/18 (88.9%) by flow cytometry (&amp;lt;10-4) and 14\/19 (73.7%) by next-generation sequencing (&amp;lt;10-6). Fourteen (63.6%) patients proceeded to HSCT. With a median follow-up of 25.3 months (95% CI 19.0-32.4), two-year disease-free (DFS) and overall survival (OS) were 48% (95% CI 24-72%); median DFS was 22.1 months (95% CI 10.4-NA), and median OS was not reached. MRD-positivity was associated with lower baseline BCL-2 dependence. Correlates of progression included acquired MCL-1 dependence, CD22 antigen escape, drug efflux gene ABCB1 expression, and oncogenic mutations. In summary, VEN+INO is safe and effective for R\/R B-ALL\/LBL, producing frequent and durable MRD-negative remissions. NCT05016947<\/jats:p>","DOI":"10.1182\/blood.2026035238","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T17:14:34Z","timestamp":1790356474000},"update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":0,"title":["Venetoclax plus Inotuzumab Ozogamicin for Relapsed and Refractory Acute Lymphoblastic Leukemia"],"prefix":"10.1182","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5781-4529","authenticated-orcid":false,"given":"Marlise R.","family":"Luskin","sequence":"first","affiliation":[{"name":"Dana-Farber Cancer Institute, Boston, Massachusetts, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia H.","family":"Keating","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Boston, Massachusetts, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5251-5299","authenticated-orcid":false,"given":"Benjamin F.","family":"Frost","sequence":"additional","affiliation":[{"name":"Brigham and Women's Hospital, Brookline, Massachusetts, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stella Louise","family":"Jaeckle","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Boston, Massachusetts, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7245-9652","authenticated-orcid":false,"given":"Shai","family":"Shimony","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Boston, Massachusetts, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yael","family":"Flamand","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Boston, Massachusetts, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2118-6302","authenticated-orcid":false,"given":"Jacqueline S.","family":"Garcia","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Boston, Massachusetts, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard M","family":"Stone","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Boston, Massachusetts, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6902-1032","authenticated-orcid":false,"given":"Matthew","family":"Booker","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Boston, Massachusetts, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6365-2490","authenticated-orcid":false,"given":"Chase M","family":"Weizer","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Boston, Massachusetts, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3327-1283","authenticated-orcid":false,"given":"Jeremy Adam","family":"Ryan","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Boston, Massachusetts, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Lee","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Boston, Massachusetts, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilene A","family":"Galinsky","sequence":"additional","affiliation":[{"name":"Dana Farber Cancer Institute, Harvard, Boston, Massachusetts, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0125-1448","authenticated-orcid":false,"given":"Sujal I","family":"Shah","sequence":"additional","affiliation":[{"name":"Brigham & Women's Hospital, Boston, Massachusetts, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Smith","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Boston, Massachusetts, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0775-8044","authenticated-orcid":false,"given":"Arpita","family":"Kulkarni","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, Massachusetts, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9134-8808","authenticated-orcid":false,"given":"Michael","family":"Tolstorukov","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Boston, Massachusetts, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9218-215X","authenticated-orcid":false,"given":"Evan C.","family":"Chen","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Boston, Massachusetts, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4515-8245","authenticated-orcid":false,"given":"Eric S","family":"Winer","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Boston, Massachusetts, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Letai","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Boston, Massachusetts, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9520-2876","authenticated-orcid":false,"given":"Mark A.","family":"Murakami","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Boston, Massachusetts, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7865-2306","authenticated-orcid":false,"given":"Daniel J","family":"DeAngelo","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Boston, Massachusetts, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","published-online":{"date-parts":[[2026,9,25]]},"container-title":["Blood 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